Theoretical Analysis of Penalized Maximum-Likelihood Patlak Parametric Image Reconstruction in Dynamic PET for Lesion Detection.

PubMed

Yang, Li; Wang, Guobao; Qi, Jinyi

2016-04-01

Detecting cancerous lesions is a major clinical application of emission tomography. In a previous work, we studied penalized maximum-likelihood (PML) image reconstruction for lesion detection in static PET. Here we extend our theoretical analysis of static PET reconstruction to dynamic PET. We study both the conventional indirect reconstruction and direct reconstruction for Patlak parametric image estimation. In indirect reconstruction, Patlak parametric images are generated by first reconstructing a sequence of dynamic PET images, and then performing Patlak analysis on the time activity curves (TACs) pixel-by-pixel. In direct reconstruction, Patlak parametric images are estimated directly from raw sinogram data by incorporating the Patlak model into the image reconstruction procedure. PML reconstruction is used in both the indirect and direct reconstruction methods. We use a channelized Hotelling observer (CHO) to assess lesion detectability in Patlak parametric images. Simplified expressions for evaluating the lesion detectability have been derived and applied to the selection of the regularization parameter value to maximize detection performance. The proposed method is validated using computer-based Monte Carlo simulations. Good agreements between the theoretical predictions and the Monte Carlo results are observed. Both theoretical predictions and Monte Carlo simulation results show the benefit of the indirect and direct methods under optimized regularization parameters in dynamic PET reconstruction for lesion detection, when compared with the conventional static PET reconstruction.

Automatic Extraction of Myocardial Mass and Volume Using Parametric Images from Dynamic Nongated PET.

PubMed

Harms, Hendrik Johannes; Stubkjær Hansson, Nils Henrik; Tolbod, Lars Poulsen; Kim, Won Yong; Jakobsen, Steen; Bouchelouche, Kirsten; Wiggers, Henrik; Frøkiaer, Jørgen; Sörensen, Jens

2016-09-01

Dynamic cardiac PET is used to quantify molecular processes in vivo. However, measurements of left ventricular (LV) mass and volume require electrocardiogram-gated PET data. The aim of this study was to explore the feasibility of measuring LV geometry using nongated dynamic cardiac PET. Thirty-five patients with aortic-valve stenosis and 10 healthy controls underwent a 27-min (11)C-acetate PET/CT scan and cardiac MRI (CMR). The controls were scanned twice to assess repeatability. Parametric images of uptake rate K1 and the blood pool were generated from nongated dynamic data. Using software-based structure recognition, the LV wall was automatically segmented from K1 images to derive functional assessments of LV mass (mLV) and wall thickness. End-systolic and end-diastolic volumes were calculated using blood pool images and applied to obtain stroke volume and LV ejection fraction (LVEF). PET measurements were compared with CMR. High, linear correlations were found for LV mass (r = 0.95), end-systolic volume (r = 0.93), and end-diastolic volume (r = 0.90), and slightly lower correlations were found for stroke volume (r = 0.74), LVEF (r = 0.81), and thickness (r = 0.78). Bland-Altman analyses showed significant differences for mLV and thickness only and an overestimation for LVEF at lower values. Intra- and interobserver correlations were greater than 0.95 for all PET measurements. PET repeatability accuracy in the controls was comparable to CMR. LV mass and volume are accurately and automatically generated from dynamic (11)C-acetate PET without electrocardiogram gating. This method can be incorporated in a standard routine without any additional workload and can, in theory, be extended to other PET tracers. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Dynamic whole body PET parametric imaging: II. Task-oriented statistical estimation

PubMed Central

Karakatsanis, Nicolas A.; Lodge, Martin A.; Zhou, Y.; Wahl, Richard L.; Rahmim, Arman

2013-01-01

In the context of oncology, dynamic PET imaging coupled with standard graphical linear analysis has been previously employed to enable quantitative estimation of tracer kinetic parameters of physiological interest at the voxel level, thus, enabling quantitative PET parametric imaging. However, dynamic PET acquisition protocols have been confined to the limited axial field-of-view (~15–20cm) of a single bed position and have not been translated to the whole-body clinical imaging domain. On the contrary, standardized uptake value (SUV) PET imaging, considered as the routine approach in clinical oncology, commonly involves multi-bed acquisitions, but is performed statically, thus not allowing for dynamic tracking of the tracer distribution. Here, we pursue a transition to dynamic whole body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. In a companion study, we presented a novel clinically feasible dynamic (4D) multi-bed PET acquisition protocol as well as the concept of whole body PET parametric imaging employing Patlak ordinary least squares (OLS) regression to estimate the quantitative parameters of tracer uptake rate Ki and total blood distribution volume V. In the present study, we propose an advanced hybrid linear regression framework, driven by Patlak kinetic voxel correlations, to achieve superior trade-off between contrast-to-noise ratio (CNR) and mean squared error (MSE) than provided by OLS for the final Ki parametric images, enabling task-based performance optimization. Overall, whether the observer's task is to detect a tumor or quantitatively assess treatment response, the proposed statistical estimation framework can be adapted to satisfy the specific task performance criteria, by adjusting the Patlak correlation-coefficient (WR) reference value. The multi-bed dynamic acquisition protocol, as optimized in the preceding companion study, was employed along with extensive Monte Carlo simulations and an initial clinical FDG patient dataset to validate and demonstrate the potential of the proposed statistical estimation methods. Both simulated and clinical results suggest that hybrid regression in the context of whole-body Patlak Ki imaging considerably reduces MSE without compromising high CNR. Alternatively, for a given CNR, hybrid regression enables larger reductions than OLS in the number of dynamic frames per bed, allowing for even shorter acquisitions of ~30min, thus further contributing to the clinical adoption of the proposed framework. Compared to the SUV approach, whole body parametric imaging can provide better tumor quantification, and can act as a complement to SUV, for the task of tumor detection. PMID:24080994

Dynamic whole-body PET parametric imaging: II. Task-oriented statistical estimation.

PubMed

Karakatsanis, Nicolas A; Lodge, Martin A; Zhou, Y; Wahl, Richard L; Rahmim, Arman

2013-10-21

In the context of oncology, dynamic PET imaging coupled with standard graphical linear analysis has been previously employed to enable quantitative estimation of tracer kinetic parameters of physiological interest at the voxel level, thus, enabling quantitative PET parametric imaging. However, dynamic PET acquisition protocols have been confined to the limited axial field-of-view (~15-20 cm) of a single-bed position and have not been translated to the whole-body clinical imaging domain. On the contrary, standardized uptake value (SUV) PET imaging, considered as the routine approach in clinical oncology, commonly involves multi-bed acquisitions, but is performed statically, thus not allowing for dynamic tracking of the tracer distribution. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. In a companion study, we presented a novel clinically feasible dynamic (4D) multi-bed PET acquisition protocol as well as the concept of whole-body PET parametric imaging employing Patlak ordinary least squares (OLS) regression to estimate the quantitative parameters of tracer uptake rate Ki and total blood distribution volume V. In the present study, we propose an advanced hybrid linear regression framework, driven by Patlak kinetic voxel correlations, to achieve superior trade-off between contrast-to-noise ratio (CNR) and mean squared error (MSE) than provided by OLS for the final Ki parametric images, enabling task-based performance optimization. Overall, whether the observer's task is to detect a tumor or quantitatively assess treatment response, the proposed statistical estimation framework can be adapted to satisfy the specific task performance criteria, by adjusting the Patlak correlation-coefficient (WR) reference value. The multi-bed dynamic acquisition protocol, as optimized in the preceding companion study, was employed along with extensive Monte Carlo simulations and an initial clinical (18)F-deoxyglucose patient dataset to validate and demonstrate the potential of the proposed statistical estimation methods. Both simulated and clinical results suggest that hybrid regression in the context of whole-body Patlak Ki imaging considerably reduces MSE without compromising high CNR. Alternatively, for a given CNR, hybrid regression enables larger reductions than OLS in the number of dynamic frames per bed, allowing for even shorter acquisitions of ~30 min, thus further contributing to the clinical adoption of the proposed framework. Compared to the SUV approach, whole-body parametric imaging can provide better tumor quantification, and can act as a complement to SUV, for the task of tumor detection.

Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application.

PubMed

Karakatsanis, Nicolas A; Lodge, Martin A; Tahari, Abdel K; Zhou, Y; Wahl, Richard L; Rahmim, Arman

2013-10-21

Static whole-body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting the axial field-of-view to ~15-20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition protocol of ~45 min total length is presented, composed of (i) an initial 6 min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (six passes × seven bed positions, each scanned for 45 s). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of ten different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole body. In addition, the total acquisition length can be reduced from 45 to ~35 min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error and the CNR metrics, resulting in enhanced task-based imaging.

Dynamic whole body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application

PubMed Central

Karakatsanis, Nicolas A.; Lodge, Martin A.; Tahari, Abdel K.; Zhou, Y.; Wahl, Richard L.; Rahmim, Arman

2013-01-01

Static whole body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single bed-coverage limiting the axial field-of-view to ~15–20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole body PET acquisition protocol of ~45min total length is presented, composed of (i) an initial 6-min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (6 passes x 7 bed positions, each scanned for 45sec). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares (OLS) Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of 10 different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole-body. In addition, the total acquisition length can be reduced from 45min to ~35min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error (MSE) and the CNR metrics, resulting in enhanced task-based imaging. PMID:24080962

Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application

NASA Astrophysics Data System (ADS)

Karakatsanis, Nicolas A.; Lodge, Martin A.; Tahari, Abdel K.; Zhou, Y.; Wahl, Richard L.; Rahmim, Arman

2013-10-01

Static whole-body PET/CT, employing the standardized uptake value (SUV), is considered the standard clinical approach to diagnosis and treatment response monitoring for a wide range of oncologic malignancies. Alternative PET protocols involving dynamic acquisition of temporal images have been implemented in the research setting, allowing quantification of tracer dynamics, an important capability for tumor characterization and treatment response monitoring. Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting the axial field-of-view to ˜15-20 cm, and have not been translated to the routine clinical context of whole-body PET imaging for the inspection of disseminated disease. Here, we pursue a transition to dynamic whole-body PET parametric imaging, by presenting, within a unified framework, clinically feasible multi-bed dynamic PET acquisition protocols and parametric imaging methods. We investigate solutions to address the challenges of: (i) long acquisitions, (ii) small number of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition protocol of ˜45 min total length is presented, composed of (i) an initial 6 min dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi-pass multi-bed PET scans (six passes × seven bed positions, each scanned for 45 s). Standard Patlak linear graphical analysis modeling was employed, coupled with image-derived plasma input function measurements. Ordinary least squares Patlak estimation was used as the baseline regression method to quantify the physiological parameters of tracer uptake rate Ki and total blood distribution volume V on an individual voxel basis. Extensive Monte Carlo simulation studies, using a wide set of published kinetic FDG parameters and GATE and XCAT platforms, were conducted to optimize the acquisition protocol from a range of ten different clinically acceptable sampling schedules examined. The framework was also applied to six FDG PET patient studies, demonstrating clinical feasibility. Both simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs) for Ki images in tumor regions with notable background FDG concentration, such as the liver, where SUV performed relatively poorly. Overall, the proposed framework enables enhanced quantification of physiological parameters across the whole body. In addition, the total acquisition length can be reduced from 45 to ˜35 min and still achieve improved or equivalent CNR compared to SUV, provided the true Ki contrast is sufficiently high. In the follow-up companion paper, a set of advanced linear regression schemes is presented to particularly address the presence of noise, and attempt to achieve a better trade-off between the mean-squared error and the CNR metrics, resulting in enhanced task-based imaging.

Quantitative assessment of dynamic PET imaging data in cancer imaging.

PubMed

Muzi, Mark; O'Sullivan, Finbarr; Mankoff, David A; Doot, Robert K; Pierce, Larry A; Kurland, Brenda F; Linden, Hannah M; Kinahan, Paul E

2012-11-01

Clinical imaging in positron emission tomography (PET) is often performed using single-time-point estimates of tracer uptake or static imaging that provides a spatial map of regional tracer concentration. However, dynamic tracer imaging can provide considerably more information about in vivo biology by delineating both the temporal and spatial pattern of tracer uptake. In addition, several potential sources of error that occur in static imaging can be mitigated. This review focuses on the application of dynamic PET imaging to measuring regional cancer biologic features and especially in using dynamic PET imaging for quantitative therapeutic response monitoring for cancer clinical trials. Dynamic PET imaging output parameters, particularly transport (flow) and overall metabolic rate, have provided imaging end points for clinical trials at single-center institutions for years. However, dynamic imaging poses many challenges for multicenter clinical trial implementations from cross-center calibration to the inadequacy of a common informatics infrastructure. Underlying principles and methodology of PET dynamic imaging are first reviewed, followed by an examination of current approaches to dynamic PET image analysis with a specific case example of dynamic fluorothymidine imaging to illustrate the approach. Copyright © 2012 Elsevier Inc. All rights reserved.

Metabolically active tumour volume segmentation from dynamic [(18)F]FLT PET studies in non-small cell lung cancer.

PubMed

Hoyng, Lieke L; Frings, Virginie; Hoekstra, Otto S; Kenny, Laura M; Aboagye, Eric O; Boellaard, Ronald

2015-01-01

Positron emission tomography (PET) with (18)F-3'-deoxy-3'-fluorothymidine ([(18)F]FLT) can be used to assess tumour proliferation. A kinetic-filtering (KF) classification algorithm has been suggested for segmentation of tumours in dynamic [(18)F]FLT PET data. The aim of the present study was to evaluate KF segmentation and its test-retest performance in [(18)F]FLT PET in non-small cell lung cancer (NSCLC) patients. Nine NSCLC patients underwent two 60-min dynamic [(18)F]FLT PET scans within 7 days prior to treatment. Dynamic scans were reconstructed with filtered back projection (FBP) as well as with ordered subsets expectation maximisation (OSEM). Twenty-eight lesions were identified by an experienced physician. Segmentation was performed using KF applied to the dynamic data set and a source-to-background corrected 50% threshold (A50%) was applied to the sum image of the last three frames (45- to 60-min p.i.). Furthermore, several adaptations of KF were tested. Both for KF and A50% test-retest (TRT) variability of metabolically active tumour volume and standard uptake value (SUV) were evaluated. KF performed better on OSEM- than on FBP-reconstructed PET images. The original KF implementation segmented 15 out of 28 lesions, whereas A50% segmented each lesion. Adapted KF versions, however, were able to segment 26 out of 28 lesions. In the best performing adapted versions, metabolically active tumour volume and SUV TRT variability was similar to those of A50%. KF misclassified certain tumour areas as vertebrae or liver tissue, which was shown to be related to heterogeneous [(18)F]FLT uptake areas within the tumour. For [(18)F]FLT PET studies in NSCLC patients, KF and A50% show comparable tumour volume segmentation performance. The KF method needs, however, a site-specific optimisation. The A50% is therefore a good alternative for tumour segmentation in NSCLC [(18)F]FLT PET studies in multicentre studies. Yet, it was observed that KF has the potential to subsegment lesions in high and low proliferative areas.

Impact of motion and partial volume effects correction on PET myocardial perfusion imaging using simultaneous PET-MR

NASA Astrophysics Data System (ADS)

Petibon, Yoann; Guehl, Nicolas J.; Reese, Timothy G.; Ebrahimi, Behzad; Normandin, Marc D.; Shoup, Timothy M.; Alpert, Nathaniel M.; El Fakhri, Georges; Ouyang, Jinsong

2017-01-01

PET is an established modality for myocardial perfusion imaging (MPI) which enables quantification of absolute myocardial blood flow (MBF) using dynamic imaging and kinetic modeling. However, heart motion and partial volume effects (PVE) significantly limit the spatial resolution and quantitative accuracy of PET MPI. Simultaneous PET-MR offers a solution to the motion problem in PET by enabling MR-based motion correction of PET data. The aim of this study was to develop a motion and PVE correction methodology for PET MPI using simultaneous PET-MR, and to assess its impact on both static and dynamic PET MPI using 18F-Flurpiridaz, a novel 18F-labeled perfusion tracer. Two dynamic 18F-Flurpiridaz MPI scans were performed on healthy pigs using a PET-MR scanner. Cardiac motion was tracked using a dedicated tagged-MRI (tMR) sequence. Motion fields were estimated using non-rigid registration of tMR images and used to calculate motion-dependent attenuation maps. Motion correction of PET data was achieved by incorporating tMR-based motion fields and motion-dependent attenuation coefficients into image reconstruction. Dynamic and static PET datasets were created for each scan. Each dataset was reconstructed as (i) Ungated, (ii) Gated (end-diastolic phase), and (iii) Motion-Corrected (MoCo), each without and with point spread function (PSF) modeling for PVE correction. Myocardium-to-blood concentration ratios (MBR) and apparent wall thickness were calculated to assess image quality for static MPI. For dynamic MPI, segment- and voxel-wise MBF values were estimated by non-linear fitting of a 2-tissue compartment model to tissue time-activity-curves. MoCo and Gating respectively decreased mean apparent wall thickness by 15.1% and 14.4% and increased MBR by 20.3% and 13.6% compared to Ungated images (P  <  0.01). Combined motion and PSF correction (MoCo-PSF) yielded 30.9% (15.7%) lower wall thickness and 82.2% (20.5%) higher MBR compared to Ungated data reconstructed without (with) PSF modeling (P  <  0.01). For dynamic PET, mean MBF across all segments were comparable for MoCo (0.72  ±  0.21 ml/min/ml) and Gating (0.69  ±  0.18 ml/min/ml). Ungated data yielded significantly lower mean MBF (0.59  ±  0.16 ml/min/ml). Mean MBF for MoCo-PSF was 0.80  ±  0.22 ml/min/ml, which was 37.9% (25.0%) higher than that obtained from Ungated data without (with) PSF correction (P  <  0.01). The developed methodology holds promise to improve the image quality and sensitivity of PET MPI studies performed using PET-MR.

Image reconstruction for PET/CT scanners: past achievements and future challenges

PubMed Central

Tong, Shan; Alessio, Adam M; Kinahan, Paul E

2011-01-01

PET is a medical imaging modality with proven clinical value for disease diagnosis and treatment monitoring. The integration of PET and CT on modern scanners provides a synergy of the two imaging modalities. Through different mathematical algorithms, PET data can be reconstructed into the spatial distribution of the injected radiotracer. With dynamic imaging, kinetic parameters of specific biological processes can also be determined. Numerous efforts have been devoted to the development of PET image reconstruction methods over the last four decades, encompassing analytic and iterative reconstruction methods. This article provides an overview of the commonly used methods. Current challenges in PET image reconstruction include more accurate quantitation, TOF imaging, system modeling, motion correction and dynamic reconstruction. Advances in these aspects could enhance the use of PET/CT imaging in patient care and in clinical research studies of pathophysiology and therapeutic interventions. PMID:21339831

Dynamic neurotransmitter interactions measured with PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiffer, W.K.; Dewey, S.L.

2001-04-02

Positron emission tomography (PET) has become a valuable interdisciplinary tool for understanding physiological, biochemical and pharmacological functions at a molecular level in living humans, whether in a healthy or diseased state. The utility of tracing chemical activity through the body transcends the fields of cardiology, oncology, neurology and psychiatry. In this, PET techniques span radiochemistry and radiopharmaceutical development to instrumentation, image analysis, anatomy and modeling. PET has made substantial contributions in each of these fields by providing a,venue for mapping dynamic functions of healthy and unhealthy human anatomy. As diverse as the disciplines it bridges, PET has provided insight intomore » an equally significant variety of psychiatric disorders. Using the unique quantitative ability of PET, researchers are now better able to non-invasively characterize normally occurring neurotransmitter interactions in the brain. With the knowledge that these interactions provide the fundamental basis for brain response, many investigators have recently focused their efforts on an examination of the communication between these chemicals in both healthy volunteers and individuals suffering from diseases classically defined as neurotransmitter specific in nature. In addition, PET can measure the biochemical dynamics of acute and sustained drug abuse. Thus, PET studies of neurotransmitter interactions enable investigators to describe a multitude of specific functional interactions in the human brain. This information can then be applied to understanding side effects that occur in response to acute and chronic drug therapy, and to designing new drugs that target multiple systems as opposed to single receptor types. Knowledge derived from PET studies can be applied to drug discovery, research and development (for review, see (Fowler et al., 1999) and (Burns et al., 1999)). Here, we will cover the most substantial contributions of PET to understanding biologically distinct neurochemical systems that interact to produce a variety of behaviors and disorders. Neurotransmitters are neither static nor isolated in their distribution. In fact, it is through interactions with other neurochemically distinct systems that the central nervous system (CNS) performs its vital role in sustaining life. Exclusive quantitative capabilities intrinsic to PET make this technology a suitable experimental tool to measure not only the regional distribution of specific receptors and their subtypes, but also the dynamic properties of neuroreceptors and their inherent influence on related neurotransmitter pathways. The ability to investigate dynamic properties in a non-invasive and reproducible manner provides a powerful tool that can extend our current knowledge of these interactions. Coupled with innovative paradigms including pharmacologic manipulations, physiologic models and reconstruction theories, knowledge derived from PET studies can greatly advance our understanding of normal and abnormal brain function.« less

Quantitative graphical analysis of simultaneous dynamic PET/MRI for assessment of prostate cancer.

PubMed

Rosenkrantz, Andrew B; Koesters, Thomas; Vahle, Anne-Kristin; Friedman, Kent; Bartlett, Rachel M; Taneja, Samir S; Ding, Yu-Shin; Logan, Jean

2015-04-01

Dynamic FDG imaging for prostate cancer characterization is limited by generally small size and low uptake in prostate tumors. Our aim in this pilot study was to explore feasibility of simultaneous PET/MRI to guide localization of prostate lesions for dynamic FDG analysis using a graphical approach. Three patients with biopsy-proven prostate cancer underwent simultaneous FDG PET/MRI, incorporating dynamic prostate imaging. Histology and multiparametric MRI findings were used to localize tumors, which in turn guided identification of tumors on FDG images. Regions of interest were manually placed on tumor and benign prostate tissue. Blood activity was extracted from a region of interest placed on the femoral artery on PET images. FDG data were analyzed by graphical analysis using the influx constant Ki (Patlak analysis) when FDG binding seemed irreversible and distribution volume VT (reversible graphical analysis) when FDG binding seemed reversible given the presence of washout. Given inherent coregistration, simultaneous acquisition facilitated use of MRI data to localize small lesions on PET and subsequent graphical analysis in all cases. In 2 cases with irreversible binding, tumor had higher Ki than benign using Patlak analysis (0.023 vs 0.006 and 0.019 vs 0.008 mL/cm3 per minute). In 1 case appearing reversible, tumor had higher VT than benign using reversible graphical analysis (0.68 vs 0.52 mL/cm3). Simultaneous PET/MRI allows localization of small prostate tumors for dynamic PET analysis. By taking advantage of inclusion of the femoral arteries in the FOV, we applied advanced PET data analysis methods beyond conventional static measures and without blood sampling.

Early-Dynamic Positron Emission Tomography (PET)/Computed Tomography and PET Angiography for Endoleak Detection After Endovascular Aneurysm Repair.

PubMed

Drescher, Robert; Gühne, Falk; Freesmeyer, Martin

2017-06-01

To propose a positron emission tomography (PET)/computed tomography (CT) protocol including early-dynamic and late-phase acquisitions to evaluate graft patency and aneurysm diameter, detect endoleaks, and rule out graft or vessel wall inflammation after endovascular aneurysm repair (EVAR) in one examination without intravenous contrast medium. Early-dynamic PET/CT of the endovascular prosthesis is performed for 180 seconds immediately after intravenous injection of F-18-fluorodeoxyglucose. Data are reconstructed in variable time frames (time periods after tracer injection) to visualize the arterial anatomy and are displayed as PET angiography or fused with CT images. Images are evaluated in view of vascular abnormalities, graft configuration, and tracer accumulation in the aneurysm sac. Whole-body PET/CT is performed 90 to 120 minutes after tracer injection. This protocol for early-dynamic PET/CT and PET angiography has the potential to evaluate vascular diseases, including the diagnosis of complications after endovascular procedures.

Combined early dynamic (18)F-FDG PET/CT and conventional whole-body (18)F-FDG PET/CT provide one-stop imaging for detecting hepatocellular carcinoma.

PubMed

Wang, Shao-Bo; Wu, Hu-Bing; Wang, Quan-Shi; Zhou, Wen-Lan; Tian, Ying; Li, Hong-Sheng; Ji, Yun-Hai; Lv, Liang

2015-06-01

It is widely accepted that conventional (18)F-FDG PET/CT (whole-body static (18)F-FDG PET/CT, WB (18)F-FDG PET/CT) has a low detection rate for hepatocellular carcinoma (HCC). We prospectively assessed the role of early dynamic (18)F-FDG PET/CT (ED (18)F-FDG PET/CT) and WB (18)F-FDG PET/CT in detecting HCC, and we quantified the added value of ED (18)F-FDG PET/CT to WB (18)F-FDG PET/CT. Twenty-two patients with 37 HCC tumors (HCCs) who underwent both a liver ED (18)F-FDG PET/CT (performed simultaneously with a 5.5 MBq/kg (18)F-FDG bolus injection and continued for 240 s) and a WB (18)F-FDG PET/CT were enrolled in the study. The WB (18)F-FDG PET/CT and ED (18)F-FDG PET/CT scans were positive in 56.7% (21/37) and 78.4% (29/37) HCCs, respectively (P<0.05). ED (18)F-FDG PET/CT in conjunction with WB (18)F-FDG PET/CT (one-stop (18)F-FDG PET/CT) improved the positive detection rates of WB and ED (18)F-FDG PET/CT alone from 56.7% and 78.4% to 91.9% (34/37) (P<0.001 and P>0.05, respectively). One-stop (18)F-FDG PET/CT appears to be useful to improve WB (18)F-FDG PET/CT for HCC detection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Nonlinear spatio-temporal filtering of dynamic PET data using a four-dimensional Gaussian filter and expectation-maximization deconvolution

NASA Astrophysics Data System (ADS)

Floberg, J. M.; Holden, J. E.

2013-02-01

We introduce a method for denoising dynamic PET data, spatio-temporal expectation-maximization (STEM) filtering, that combines four-dimensional Gaussian filtering with EM deconvolution. The initial Gaussian filter suppresses noise at a broad range of spatial and temporal frequencies and EM deconvolution quickly restores the frequencies most important to the signal. We aim to demonstrate that STEM filtering can improve variance in both individual time frames and in parametric images without introducing significant bias. We evaluate STEM filtering with a dynamic phantom study, and with simulated and human dynamic PET studies of a tracer with reversible binding behaviour, [C-11]raclopride, and a tracer with irreversible binding behaviour, [F-18]FDOPA. STEM filtering is compared to a number of established three and four-dimensional denoising methods. STEM filtering provides substantial improvements in variance in both individual time frames and in parametric images generated with a number of kinetic analysis techniques while introducing little bias. STEM filtering does bias early frames, but this does not affect quantitative parameter estimates. STEM filtering is shown to be superior to the other simple denoising methods studied. STEM filtering is a simple and effective denoising method that could be valuable for a wide range of dynamic PET applications.

Integrating Dynamic Positron Emission Tomography and Conventional Pharmacokinetic Studies to Delineate Plasma and Tumor Pharmacokinetics of FAU, a Prodrug Bioactivated by Thymidylate Synthase.

PubMed

Li, Jing; Kim, Seongho; Shields, Anthony F; Douglas, Kirk A; McHugh, Christopher I; Lawhorn-Crews, Jawana M; Wu, Jianmei; Mangner, Thomas J; LoRusso, Patricia M

2016-11-01

FAU, a pyrimidine nucleotide analogue, is a prodrug bioactivated by intracellular thymidylate synthase to form FMAU, which is incorporated into DNA, causing cell death. This study presents a model-based approach to integrating dynamic positron emission tomography (PET) and conventional plasma pharmacokinetic studies to characterize the plasma and tissue pharmacokinetics of FAU and FMAU. Twelve cancer patients were enrolled into a phase 1 study, where conventional plasma pharmacokinetic evaluation of therapeutic FAU (50-1600 mg/m 2 ) and dynamic PET assessment of 18 F-FAU were performed. A parent-metabolite population pharmacokinetic model was developed to simultaneously fit PET-derived tissue data and conventional plasma pharmacokinetic data. The developed model enabled separation of PET-derived total tissue concentrations into the parent drug and metabolite components. The model provides quantitative, mechanistic insights into the bioactivation of FAU and retention of FMAU in normal and tumor tissues and has potential utility to predict tumor responsiveness to FAU treatment. © 2016, The American College of Clinical Pharmacology.

Radiotherapy volume delineation using dynamic [18F]-FDG PET/CT imaging in patients with oropharyngeal cancer: a pilot study.

PubMed

Silvoniemi, Antti; Din, Mueez U; Suilamo, Sami; Shepherd, Tony; Minn, Heikki

2016-11-01

Delineation of gross tumour volume in 3D is a critical step in the radiotherapy (RT) treatment planning for oropharyngeal cancer (OPC). Static [ 18 F]-FDG PET/CT imaging has been suggested as a method to improve the reproducibility of tumour delineation, but it suffers from low specificity. We undertook this pilot study in which dynamic features in time-activity curves (TACs) of [ 18 F]-FDG PET/CT images were applied to help the discrimination of tumour from inflammation and adjacent normal tissue. Five patients with OPC underwent dynamic [ 18 F]-FDG PET/CT imaging in treatment position. Voxel-by-voxel analysis was performed to evaluate seven dynamic features developed with the knowledge of differences in glucose metabolism in different tissue types and visual inspection of TACs. The Gaussian mixture model and K-means algorithms were used to evaluate the performance of the dynamic features in discriminating tumour voxels compared to the performance of standardized uptake values obtained from static imaging. Some dynamic features showed a trend towards discrimination of different metabolic areas but lack of consistency means that clinical application is not recommended based on these results alone. Impact of inflammatory tissue remains a problem for volume delineation in RT of OPC, but a simple dynamic imaging protocol proved practicable and enabled simple data analysis techniques that show promise for complementing the information in static uptake values.

Optimization of PET-MR Registrations for Nonhuman Primates Using Mutual Information Measures: A Multi-Transform Method (MTM)

PubMed Central

Sandiego, Christine M.; Weinzimmer, David; Carson, Richard E.

2012-01-01

An important step in PET brain kinetic analysis is the registration of functional data to an anatomical MR image. Typically, PET-MR registrations in nonhuman primate neuroreceptor studies used PET images acquired early post-injection, (e.g., 0–10 min) to closely resemble the subject’s MR image. However, a substantial fraction of these registrations (~25%) fail due to the differences in kinetics and distribution for various radiotracer studies and conditions (e.g., blocking studies). The Multi-Transform Method (MTM) was developed to improve the success of registrations between PET and MR images. Two algorithms were evaluated, MTM-I and MTM-II. The approach involves creating multiple transformations by registering PET images of different time intervals, from a dynamic study, to a single reference (i.e., MR image) (MTM-I) or to multiple reference images (i.e., MR and PET images pre-registered to the MR) (MTM-II). Normalized mutual information was used to compute similarity between the transformed PET images and the reference image(s) to choose the optimal transformation. This final transformation is used to map the dynamic dataset into the animal’s anatomical MR space, required for kinetic analysis. The chosen transformed from MTM-I and MTM-II were evaluated using visual rating scores to assess the quality of spatial alignment between the resliced PET and reference. One hundred twenty PET datasets involving eleven different tracers from 3 different scanners were used to evaluate the MTM algorithms. Studies were performed with baboons and rhesus monkeys on the HR+, HRRT, and Focus-220. Successful transformations increased from 77.5%, 85.8%, to 96.7% using the 0–10 min method, MTM-I, and MTM-II, respectively, based on visual rating scores. The Multi-Transform Methods proved to be a robust technique for PET-MR registrations for a wide range of PET studies. PMID:22926293

Extracting a respiratory signal from raw dynamic PET data that contain tracer kinetics.

PubMed

Schleyer, P J; Thielemans, K; Marsden, P K

2014-08-07

Data driven gating (DDG) methods provide an alternative to hardware based respiratory gating for PET imaging. Several existing DDG approaches obtain a respiratory signal by observing the change in PET-counts within specific regions of acquired PET data. Currently, these methods do not allow for tracer kinetics which can interfere with the respiratory signal and introduce error. In this work, we produced a DDG method for dynamic PET studies that exhibit tracer kinetics. Our method is based on an existing approach that uses frequency-domain analysis to locate regions within raw PET data that are subject to respiratory motion. In the new approach, an optimised non-stationary short-time Fourier transform was used to create a time-varying 4D map of motion affected regions. Additional processing was required to ensure that the relationship between the sign of the respiratory signal and the physical direction of movement remained consistent for each temporal segment of the 4D map. The change in PET-counts within the 4D map during the PET acquisition was then used to generate a respiratory curve. Using 26 min dynamic cardiac NH3 PET acquisitions which included a hardware derived respiratory measurement, we show that tracer kinetics can severely degrade the respiratory signal generated by the original DDG method. In some cases, the transition of tracer from the liver to the lungs caused the respiratory signal to invert. The new approach successfully compensated for tracer kinetics and improved the correlation between the data-driven and hardware based signals. On average, good correlation was maintained throughout the PET acquisitions.

Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR

NASA Astrophysics Data System (ADS)

Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A.; Costes, Nicolas; Hammers, Alexander

2017-04-01

In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This work demonstrates that inaccuracies in attenuation maps can induce bias in dynamic brain PET studies. Multi-atlas attenuation correction with MaxProb enables quantification on hybrid PET-MR scanners, eschewing the need for CT.

Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR.

PubMed

Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A; Costes, Nicolas; Hammers, Alexander

2017-04-07

In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [ 18 F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [ 18 F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BP ND ). On static [ 18 F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [ 18 F]MPPF, most regional errors on BP ND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This work demonstrates that inaccuracies in attenuation maps can induce bias in dynamic brain PET studies. Multi-atlas attenuation correction with MaxProb enables quantification on hybrid PET-MR scanners, eschewing the need for CT.

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

PubMed

Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

2018-02-01

The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Efficient robust reconstruction of dynamic PET activity maps with radioisotope decay constraints.

PubMed

Gao, Fei; Liu, Huafeng; Shi, Pengcheng

2010-01-01

Dynamic PET imaging performs sequence of data acquisition in order to provide visualization and quantification of physiological changes in specific tissues and organs. The reconstruction of activity maps is generally the first step in dynamic PET. State space Hinfinity approaches have been proved to be a robust method for PET image reconstruction where, however, temporal constraints are not considered during the reconstruction process. In addition, the state space strategies for PET image reconstruction have been computationally prohibitive for practical usage because of the need for matrix inversion. In this paper, we present a minimax formulation of the dynamic PET imaging problem where a radioisotope decay model is employed as physics-based temporal constraints on the photon counts. Furthermore, a robust steady state Hinfinity filter is developed to significantly improve the computational efficiency with minimal loss of accuracy. Experiments are conducted on Monte Carlo simulated image sequences for quantitative analysis and validation.

Matching the reaction-diffusion simulation to dynamic [18F]FMISO PET measurements in tumors: extension to a flow-limited oxygen-dependent model.

PubMed

Shi, Kuangyu; Bayer, Christine; Gaertner, Florian C; Astner, Sabrina T; Wilkens, Jan J; Nüsslin, Fridtjof; Vaupel, Peter; Ziegler, Sibylle I

2017-02-01

Positron-emission tomography (PET) with hypoxia specific tracers provides a noninvasive method to assess the tumor oxygenation status. Reaction-diffusion models have advantages in revealing the quantitative relation between in vivo imaging and the tumor microenvironment. However, there is no quantitative comparison of the simulation results with the real PET measurements yet. The lack of experimental support hampers further applications of computational simulation models. This study aims to compare the simulation results with a preclinical [ 18 F]FMISO PET study and to optimize the reaction-diffusion model accordingly. Nude mice with xenografted human squamous cell carcinomas (CAL33) were investigated with a 2 h dynamic [ 18 F]FMISO PET followed by immunofluorescence staining using the hypoxia marker pimonidazole and the endothelium marker CD 31. A large data pool of tumor time-activity curves (TAC) was simulated for each mouse by feeding the arterial input function (AIF) extracted from experiments into the model with different configurations of the tumor microenvironment. A measured TAC was considered to match a simulated TAC when the difference metric was below a certain, noise-dependent threshold. As an extension to the well-established Kelly model, a flow-limited oxygen-dependent (FLOD) model was developed to improve the matching between measurements and simulations. The matching rate between the simulated TACs of the Kelly model and the mouse PET data ranged from 0 to 28.1% (on average 9.8%). By modifying the Kelly model to an FLOD model, the matching rate between the simulation and the PET measurements could be improved to 41.2-84.8% (on average 64.4%). Using a simulation data pool and a matching strategy, we were able to compare the simulated temporal course of dynamic PET with in vivo measurements. By modifying the Kelly model to a FLOD model, the computational simulation was able to approach the dynamic [ 18 F]FMISO measurements in the investigated tumors.

Utility of early dynamic and delayed post-diuretic 18F-FDG PET/CT SUVmax in predicting tumour grade and T-stage of urinary bladder carcinoma: results from a prospective single centre study.

PubMed

Sharma, Abhishek; Mete, Uttam K; Sood, Ashwani; Kakkar, Nandita; Gorla, Arun K R; Mittal, Bhagwant R

2017-04-01

Accurate pre-treatment grading and staging of bladder cancer are vital for better therapeutic decision and prognosis. The aim of the present study was to evaluate the correlation between maximum standardized uptake value (SUV max ) calculated during early dynamic and post-diuretic fluorine-18 fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT studies with grade and pT-stage of bladder cancer. 39 patients with suspected/proven bladder carcinoma underwent 10-min early dynamic pelvic imaging and delayed post-diuretic whole-body FDG PET/CT imaging. SUV max of the lesions derived from both studies was compared with grade and pT-stage. Relationship of SUV max with grade and pT-stage was analyzed using independent sample t-test and analysis of variance. SUV max of the early dynamic imaging showing tumour perfusion was independent from the SUV max of delayed imaging. High-grade tumours showed higher SUV max than low-grade tumours in the early dynamic imaging (5.4 ± 1.4 vs 4.7 ± 1.6; p-value 0.144) with statistically significant higher value in Stage pT1 tumours (6.8 ± 0.8 vs 5.5 ± 1.2; p-value 0.04). Non-invasive pTa tumours had significantly less SUV max than higher stage tumours during early dynamic imaging [F(4,29) = 6.860, p 0.001]. Early dynamic imaging may have a role in predicting the grade and aggressiveness of the bladder tumours and thus can help in treatment planning and prognostication. Advances in knowledge: Dynamic PET/CT is a limitedly explored imaging technique. This prospective pilot study demonstrates the utility of this modality as a potential adjunct to standard FDG PET/CT imaging in predicting the grade and aggressiveness of the bladder tumours and thus can impact the patient management.

Dynamic cardiac PET imaging: extraction of time-activity curves using ICA and a generalized Gaussian distribution model.

PubMed

Mabrouk, Rostom; Dubeau, François; Bentabet, Layachi

2013-01-01

Kinetic modeling of metabolic and physiologic cardiac processes in small animals requires an input function (IF) and a tissue time-activity curves (TACs). In this paper, we present a mathematical method based on independent component analysis (ICA) to extract the IF and the myocardium's TACs directly from dynamic positron emission tomography (PET) images. The method assumes a super-Gaussian distribution model for the blood activity, and a sub-Gaussian distribution model for the tissue activity. Our appreach was applied on 22 PET measurement sets of small animals, which were obtained from the three most frequently used cardiac radiotracers, namely: desoxy-fluoro-glucose ((18)F-FDG), [(13)N]-ammonia, and [(11)C]-acetate. Our study was extended to PET human measurements obtained with the Rubidium-82 ((82) Rb) radiotracer. The resolved mathematical IF values compare favorably to those derived from curves extracted from regions of interest (ROI), suggesting that the procedure presents a reliable alternative to serial blood sampling for small-animal cardiac PET studies.

Rheological Properties and Foaming Behavior of Poly(Ethylene Terephthalates) Modified with Pyromellitic Dianhydride

NASA Astrophysics Data System (ADS)

Yang, Zhao-Ping; Xin, Chun-Ling; Guo, Ya-Feng; Luo, Yi-Wei; He, Ya-Dong

2016-05-01

Improving the melt viscoelasticity of poly(ethylene terephthalate) (PET) is a well-known method to obtain foamable PET. The aim of this study is to prepare high melt strength PET and evaluate the influence of rheological properties of PET on the foaming behavior. For this purpose, pyromelliticdianhydride was used as the chain extender to modify a linear PET through melt reactive processing. The rheological properties of the unmodified and modified PETs were measured by a dynamic rheometer. Results showed that the modified PET had higher complex viscosity than the unmodified one. Furthermore, the batch foaming by using supercritical CO2 as a blowing agent was carried to evaluate the foamability of modified PETs. It was found that an enlarged foaming temperature window was obtained for modified PETs compared to unmodified PET. Moreover, the modified PETs foams exhibited higher expansion ratio, smaller cell size and higher cell density at high temperatures than the neat PET.

Solitary pulmonary nodules: Comparison of dynamic first-pass contrast-enhanced perfusion area-detector CT, dynamic first-pass contrast-enhanced MR imaging, and FDG PET/CT.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Seki, Shinichiro; Tsubakimoto, Maho; Fujisawa, Yasuko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2015-02-01

To prospectively compare the capabilities of dynamic perfusion area-detector computed tomography (CT), dynamic magnetic resonance (MR) imaging, and positron emission tomography (PET) combined with CT (PET/CT) with use of fluorine 18 fluorodeoxyglucose (FDG) for the diagnosis of solitary pulmonary nodules. The institutional review board approved this study, and written informed consent was obtained from each subject. A total of 198 consecutive patients with 218 nodules prospectively underwent dynamic perfusion area-detector CT, dynamic MR imaging, FDG PET/CT, and microbacterial and/or pathologic examinations. Nodules were classified into three groups: malignant nodules (n = 133) and benign nodules with low (n = 53) or high (n = 32) biologic activity. Total perfusion was determined with dual-input maximum slope models at area-detector CT, maximum and slope of enhancement ratio at MR imaging, and maximum standardized uptake value (SUVmax) at PET/CT. Next, all indexes for malignant and benign nodules were compared with the Tukey honest significant difference test. Then, receiver operating characteristic analysis was performed for each index. Finally, sensitivity, specificity, and accuracy were compared with the McNemar test. All indexes showed significant differences between malignant nodules and benign nodules with low biologic activity (P < .0001). The area under the receiver operating characteristic curve for total perfusion was significantly larger than that for other indexes (.0006 ≤ P ≤ .04). The specificity and accuracy of total perfusion were significantly higher than those of maximum relative enhancement ratio (specificity, P < .0001; accuracy, P < .0001), slope of enhancement ratio (specificity, P < .0001; accuracy, P < .0001), and SUVmax (specificity, P < .0001; accuracy, P < .0001). Dynamic perfusion area-detector CT is more specific and accurate than dynamic MR imaging and FDG PET/CT in the diagnosis of solitary pulmonary nodules in routine clinical practice. © RSNA, 2014.

Characteristics of time-activity curves obtained from dynamic 11C-methionine PET in common primary brain tumors.

PubMed

Nomura, Yuichi; Asano, Yoshitaka; Shinoda, Jun; Yano, Hirohito; Ikegame, Yuka; Kawasaki, Tomohiro; Nakayama, Noriyuki; Maruyama, Takashi; Muragaki, Yoshihiro; Iwama, Toru

2018-07-01

The aim of this study was to assess whether dynamic PET with 11 C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors. One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE). The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P < 0.05). The SLOPE in the late phase was significantly lower in tumors that included an oligodendroglial component compared to astrocytic tumors (P < 0.001). When we set the cutoff of the SLOPE in the late phase to - 0.04 h -1 for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731. The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging.

PubMed

Shi, Ximin; Li, Nan; Ding, Haiyan; Dang, Yonghong; Hu, Guilan; Liu, Shuai; Cui, Jie; Zhang, Yue; Li, Fang; Zhang, Hui; Huo, Li

2018-01-01

Kinetic modeling of dynamic 11 C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11 C-acetate cardiac PET imaging. Suspected alcoholic cardiomyopathy patients ( N = 24) underwent 11 C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K 1 and k 2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11 C-acetate PET images. Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K 1 and k 2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. All the tested reconstruction algorithms performed similarly for quantitative analysis of 11 C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11 C-acetate kinetic analysis.

Bringing physiology into PET of the liver.

PubMed

Keiding, Susanne

2012-03-01

Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time-activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time-activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time-activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time-activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic (18)F-FDG PET/CT recording. Later, steady-state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, (18)F-FDG and (11)C-palmitate.

Longitudinal studies of the 18F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT.

PubMed

Sachpekidis, Christos; Anwar, Hoda; Winkler, Julia K; Kopp-Schneider, Annette; Larribere, Lionel; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-06-05

Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-( 18 F)fluoro-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy. 25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with 18 F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT). The evaluation of dPET/CT studies was based on semi-quantitative (standardized uptake value, SUV) calculation as well as quantitative analysis, based on two-tissue compartment modeling and a fractal approach. Patients' best clinical response, assessed at a mean of 59 weeks, was used as reference. According to their best clinical response, patients were dichotomized in those demonstrating clinical benefit (CB, n = 16 patients) and those demonstrating no clinical benefit (no-CB, n = 9 patients). No statistically significant differences were observed between CB and no-CB regarding either semi-quantitative or quantitative parameters in all scans. On contrary, the application of the recently introduced PET response evaluation criteria for immunotherapy (PERCIMT) led to a correct classification rate of 84% (21/25 patients). Quantitative analysis of 18 F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response.

Diagnosis of glioma recurrence using multiparametric dynamic 18F-fluoroethyl-tyrosine PET-MRI.

PubMed

Pyka, Thomas; Hiob, Daniela; Preibisch, Christine; Gempt, Jens; Wiestler, Benedikt; Schlegel, Jürgen; Straube, Christoph; Zimmer, Claus

2018-06-01

To investigate the value of combined 18F-fluorethyltyrosine-(FET)-PET/MRI for differentiation between recurrence and treatment-related changes in glioma patients. 63 lesions suggestive of recurrence in 47 glioma patients were retrospectively identified. All patients had a dynamic FET scan, as well as morphologic MRI, PWI and DWI on a hybrid PET/MRI scanner. Lesions suggestive of recurrence were marked. ROC analysis was performed univariately and on parameter combination. 50 lesions were classified as recurrence, 13 as radiation necrosis. Diagnosis was based on histology in 23 and follow-up imaging in 40 cases. Sensitivities and specificities for static PET were 80 and 85%, 66% and 77% for PWI, 62 and 77% for DWI and 64 and 79% for PET time-to-peak. AUC was 0.86 (p < 0.001) for static PET, 0.73 (p = 0.013) for PWI, 0.70 (p = 0.030) for DWI and 0.73 (p < 0.001) for dynamic PET. Multiparametric analysis resulted in an AUC of 0.89, notably yielding sensitivity of 76% vs. 56% for PET alone at 100% specificity. Simultaneous dynamic FET-PET/MRI was reliably feasible for imaging of recurrent glioma. While all modalities were able to discriminate between recurrence and treatment-related changes, multiparametric analysis added value especially when high specificity was demanded. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional segmentation of dynamic PET studies: Open source implementation and validation of a leader-follower-based algorithm.

PubMed

Mateos-Pérez, José María; Soto-Montenegro, María Luisa; Peña-Zalbidea, Santiago; Desco, Manuel; Vaquero, Juan José

2016-02-01

We present a novel segmentation algorithm for dynamic PET studies that groups pixels according to the similarity of their time-activity curves. Sixteen mice bearing a human tumor cell line xenograft (CH-157MN) were imaged with three different (68)Ga-DOTA-peptides (DOTANOC, DOTATATE, DOTATOC) using a small animal PET-CT scanner. Regional activities (input function and tumor) were obtained after manual delineation of regions of interest over the image. The algorithm was implemented under the jClustering framework and used to extract the same regional activities as in the manual approach. The volume of distribution in the tumor was computed using the Logan linear method. A Kruskal-Wallis test was used to investigate significant differences between the manually and automatically obtained volumes of distribution. The algorithm successfully segmented all the studies. No significant differences were found for the same tracer across different segmentation methods. Manual delineation revealed significant differences between DOTANOC and the other two tracers (DOTANOC - DOTATATE, p=0.020; DOTANOC - DOTATOC, p=0.033). Similar differences were found using the leader-follower algorithm. An open implementation of a novel segmentation method for dynamic PET studies is presented and validated in rodent studies. It successfully replicated the manual results obtained in small-animal studies, thus making it a reliable substitute for this task and, potentially, for other dynamic segmentation procedures. Copyright © 2016 Elsevier Ltd. All rights reserved.

Movement Correction Method for Human Brain PET Images: Application to Quantitative Analysis of Dynamic [18F]-FDDNP Scans

PubMed Central

Wardak, Mirwais; Wong, Koon-Pong; Shao, Weber; Dahlbom, Magnus; Kepe, Vladimir; Satyamurthy, Nagichettiar; Small, Gary W.; Barrio, Jorge R.; Huang, Sung-Cheng

2010-01-01

Head movement during a PET scan (especially, dynamic scan) can affect both the qualitative and quantitative aspects of an image, making it difficult to accurately interpret the results. The primary objective of this study was to develop a retrospective image-based movement correction (MC) method and evaluate its implementation on dynamic [18F]-FDDNP PET images of cognitively intact controls and patients with Alzheimer’s disease (AD). Methods Dynamic [18F]-FDDNP PET images, used for in vivo imaging of beta-amyloid plaques and neurofibrillary tangles, were obtained from 12 AD and 9 age-matched controls. For each study, a transmission scan was first acquired for attenuation correction. An accurate retrospective MC method that corrected for transmission-emission misalignment as well as emission-emission misalignment was applied to all studies. No restriction was assumed for zero movement between the transmission scan and first emission scan. Logan analysis with cerebellum as the reference region was used to estimate various regional distribution volume ratio (DVR) values in the brain before and after MC. Discriminant analysis was used to build a predictive model for group membership, using data with and without MC. Results MC improved the image quality and quantitative values in [18F]-FDDNP PET images. In this subject population, medial temporal (MTL) did not show a significant difference between controls and AD before MC. However, after MC, significant differences in DVR values were seen in frontal, parietal, posterior cingulate (PCG), MTL, lateral temporal (LTL), and global between the two groups (P < 0.05). In controls and AD, the variability of regional DVR values (as measured by the coefficient of variation) decreased on average by >18% after MC. Mean DVR separation between controls and ADs was higher in frontal, MTL, LTL and global after MC. Group classification by discriminant analysis based on [18F]-FDDNP DVR values was markedly improved after MC. Conclusion The streamlined and easy to use MC method presented in this work significantly improves the image quality and the measured tracer kinetics of [18F]-FDDNP PET images. The proposed MC method has the potential to be applied to PET studies on patients having other disorders (e.g., Down syndrome and Parkinson’s disease) and to brain PET scans with other molecular imaging probes. PMID:20080894

Direct parametric reconstruction in dynamic PET myocardial perfusion imaging: in vivo studies.

PubMed

Petibon, Yoann; Rakvongthai, Yothin; El Fakhri, Georges; Ouyang, Jinsong

2017-05-07

Dynamic PET myocardial perfusion imaging (MPI) used in conjunction with tracer kinetic modeling enables the quantification of absolute myocardial blood flow (MBF). However, MBF maps computed using the traditional indirect method (i.e. post-reconstruction voxel-wise fitting of kinetic model to PET time-activity-curves-TACs) suffer from poor signal-to-noise ratio (SNR). Direct reconstruction of kinetic parameters from raw PET projection data has been shown to offer parametric images with higher SNR compared to the indirect method. The aim of this study was to extend and evaluate the performance of a direct parametric reconstruction method using in vivo dynamic PET MPI data for the purpose of quantifying MBF. Dynamic PET MPI studies were performed on two healthy pigs using a Siemens Biograph mMR scanner. List-mode PET data for each animal were acquired following a bolus injection of ~7-8 mCi of 18 F-flurpiridaz, a myocardial perfusion agent. Fully-3D dynamic PET sinograms were obtained by sorting the coincidence events into 16 temporal frames covering ~5 min after radiotracer administration. Additionally, eight independent noise realizations of both scans-each containing 1/8th of the total number of events-were generated from the original list-mode data. Dynamic sinograms were then used to compute parametric maps using the conventional indirect method and the proposed direct method. For both methods, a one-tissue compartment model accounting for spillover from the left and right ventricle blood-pools was used to describe the kinetics of 18 F-flurpiridaz. An image-derived arterial input function obtained from a TAC taken in the left ventricle cavity was used for tracer kinetic analysis. For the indirect method, frame-by-frame images were estimated using two fully-3D reconstruction techniques: the standard ordered subset expectation maximization (OSEM) reconstruction algorithm on one side, and the one-step late maximum a posteriori (OSL-MAP) algorithm on the other side, which incorporates a quadratic penalty function. The parametric images were then calculated using voxel-wise weighted least-square fitting of the reconstructed myocardial PET TACs. For the direct method, parametric images were estimated directly from the dynamic PET sinograms using a maximum a posteriori (MAP) parametric reconstruction algorithm which optimizes an objective function comprised of the Poisson log-likelihood term, the kinetic model and a quadratic penalty function. Maximization of the objective function with respect to each set of parameters was achieved using a preconditioned conjugate gradient algorithm with a specifically developed pre-conditioner. The performance of the direct method was evaluated by comparing voxel- and segment-wise estimates of [Formula: see text], the tracer transport rate (ml · min -1 · ml -1 ), to those obtained using the indirect method applied to both OSEM and OSL-MAP dynamic reconstructions. The proposed direct reconstruction method produced [Formula: see text] maps with visibly lower noise than the indirect method based on OSEM and OSL-MAP reconstructions. At normal count levels, the direct method was shown to outperform the indirect method based on OSL-MAP in the sense that at matched level of bias, reduced regional noise levels were obtained. At lower count levels, the direct method produced [Formula: see text] estimates with significantly lower standard deviation across noise realizations than the indirect method based on OSL-MAP at matched bias level. In all cases, the direct method yielded lower noise and standard deviation than the indirect method based on OSEM. Overall, the proposed direct reconstruction offered a better bias-variance tradeoff than the indirect method applied to either OSEM and OSL-MAP. Direct parametric reconstruction as applied to in vivo dynamic PET MPI data is therefore a promising method for producing MBF maps with lower variance.

Direct parametric reconstruction in dynamic PET myocardial perfusion imaging: in-vivo studies

PubMed Central

Petibon, Yoann; Rakvongthai, Yothin; Fakhri, Georges El; Ouyang, Jinsong

2017-01-01

Dynamic PET myocardial perfusion imaging (MPI) used in conjunction with tracer kinetic modeling enables the quantification of absolute myocardial blood flow (MBF). However, MBF maps computed using the traditional indirect method (i.e. post-reconstruction voxel-wise fitting of kinetic model to PET time-activity-curves -TACs) suffer from poor signal-to-noise ratio (SNR). Direct reconstruction of kinetic parameters from raw PET projection data has been shown to offer parametric images with higher SNR compared to the indirect method. The aim of this study was to extend and evaluate the performance of a direct parametric reconstruction method using in-vivo dynamic PET MPI data for the purpose of quantifying MBF. Dynamic PET MPI studies were performed on two healthy pigs using a Siemens Biograph mMR scanner. List-mode PET data for each animal were acquired following a bolus injection of ~7-8 mCi of 18F-flurpiridaz, a myocardial perfusion agent. Fully-3D dynamic PET sinograms were obtained by sorting the coincidence events into 16 temporal frames covering ~5 min after radiotracer administration. Additionally, eight independent noise realizations of both scans - each containing 1/8th of the total number of events - were generated from the original list-mode data. Dynamic sinograms were then used to compute parametric maps using the conventional indirect method and the proposed direct method. For both methods, a one-tissue compartment model accounting for spillover from the left and right ventricle blood-pools was used to describe the kinetics of 18F-flurpiridaz. An image-derived arterial input function obtained from a TAC taken in the left ventricle cavity was used for tracer kinetic analysis. For the indirect method, frame-by-frame images were estimated using two fully-3D reconstruction techniques: the standard Ordered Subset Expectation Maximization (OSEM) reconstruction algorithm on one side, and the One-Step Late Maximum a Posteriori (OSL-MAP) algorithm on the other side, which incorporates a quadratic penalty function. The parametric images were then calculated using voxel-wise weighted least-square fitting of the reconstructed myocardial PET TACs. For the direct method, parametric images were estimated directly from the dynamic PET sinograms using a maximum a posteriori (MAP) parametric reconstruction algorithm which optimizes an objective function comprised of the Poisson log-likelihood term, the kinetic model and a quadratic penalty function. Maximization of the objective function with respect to each set of parameters was achieved using a preconditioned conjugate gradient algorithm with a specifically developed pre-conditioner. The performance of the direct method was evaluated by comparing voxel- and segment-wise estimates of K1, the tracer transport rate (mL.min−1.mL−1), to those obtained using the indirect method applied to both OSEM and OSL-MAP dynamic reconstructions. The proposed direct reconstruction method produced K1 maps with visibly lower noise than the indirect method based on OSEM and OSL-MAP reconstructions. At normal count levels, the direct method was shown to outperform the indirect method based on OSL-MAP in the sense that at matched level of bias, reduced regional noise levels were obtained. At lower count levels, the direct method produced K1 estimates with significantly lower standard deviation across noise realizations than the indirect method based on OSL-MAP at matched bias level. In all cases, the direct method yielded lower noise and standard deviation than the indirect method based on OSEM. Overall, the proposed direct reconstruction offered a better bias-variance tradeoff than the indirect method applied to either OSEM and OSL-MAP. Direct parametric reconstruction as applied to in-vivo dynamic PET MPI data is therefore a promising method for producing MBF maps with lower variance. PMID:28379843

Direct parametric reconstruction in dynamic PET myocardial perfusion imaging: in vivo studies

NASA Astrophysics Data System (ADS)

Petibon, Yoann; Rakvongthai, Yothin; El Fakhri, Georges; Ouyang, Jinsong

2017-05-01

Dynamic PET myocardial perfusion imaging (MPI) used in conjunction with tracer kinetic modeling enables the quantification of absolute myocardial blood flow (MBF). However, MBF maps computed using the traditional indirect method (i.e. post-reconstruction voxel-wise fitting of kinetic model to PET time-activity-curves-TACs) suffer from poor signal-to-noise ratio (SNR). Direct reconstruction of kinetic parameters from raw PET projection data has been shown to offer parametric images with higher SNR compared to the indirect method. The aim of this study was to extend and evaluate the performance of a direct parametric reconstruction method using in vivo dynamic PET MPI data for the purpose of quantifying MBF. Dynamic PET MPI studies were performed on two healthy pigs using a Siemens Biograph mMR scanner. List-mode PET data for each animal were acquired following a bolus injection of ~7-8 mCi of 18F-flurpiridaz, a myocardial perfusion agent. Fully-3D dynamic PET sinograms were obtained by sorting the coincidence events into 16 temporal frames covering ~5 min after radiotracer administration. Additionally, eight independent noise realizations of both scans—each containing 1/8th of the total number of events—were generated from the original list-mode data. Dynamic sinograms were then used to compute parametric maps using the conventional indirect method and the proposed direct method. For both methods, a one-tissue compartment model accounting for spillover from the left and right ventricle blood-pools was used to describe the kinetics of 18F-flurpiridaz. An image-derived arterial input function obtained from a TAC taken in the left ventricle cavity was used for tracer kinetic analysis. For the indirect method, frame-by-frame images were estimated using two fully-3D reconstruction techniques: the standard ordered subset expectation maximization (OSEM) reconstruction algorithm on one side, and the one-step late maximum a posteriori (OSL-MAP) algorithm on the other side, which incorporates a quadratic penalty function. The parametric images were then calculated using voxel-wise weighted least-square fitting of the reconstructed myocardial PET TACs. For the direct method, parametric images were estimated directly from the dynamic PET sinograms using a maximum a posteriori (MAP) parametric reconstruction algorithm which optimizes an objective function comprised of the Poisson log-likelihood term, the kinetic model and a quadratic penalty function. Maximization of the objective function with respect to each set of parameters was achieved using a preconditioned conjugate gradient algorithm with a specifically developed pre-conditioner. The performance of the direct method was evaluated by comparing voxel- and segment-wise estimates of {{K}1} , the tracer transport rate (ml · min-1 · ml-1), to those obtained using the indirect method applied to both OSEM and OSL-MAP dynamic reconstructions. The proposed direct reconstruction method produced {{K}1} maps with visibly lower noise than the indirect method based on OSEM and OSL-MAP reconstructions. At normal count levels, the direct method was shown to outperform the indirect method based on OSL-MAP in the sense that at matched level of bias, reduced regional noise levels were obtained. At lower count levels, the direct method produced {{K}1} estimates with significantly lower standard deviation across noise realizations than the indirect method based on OSL-MAP at matched bias level. In all cases, the direct method yielded lower noise and standard deviation than the indirect method based on OSEM. Overall, the proposed direct reconstruction offered a better bias-variance tradeoff than the indirect method applied to either OSEM and OSL-MAP. Direct parametric reconstruction as applied to in vivo dynamic PET MPI data is therefore a promising method for producing MBF maps with lower variance.

Interaction of proflavin with aromatic amines in homogeneous and micellar media: Photoinduced electron transfer probed by magnetic field effect

NASA Astrophysics Data System (ADS)

Chakraborty, Brotati; Basu, Samita

2010-02-01

Photoinduced electron transfer (PET) between proflavin (PF +) and two aromatic amines viz., dimethylaniline (DMA) and 4,4'-bis(dimethylamino)diphenylmethane (DMDPM) is studied in homogeneous and heterogeneous media using steady-state as well as time-resolved fluorescence spectroscopy and laser flash photolysis with an associated magnetic field. Ionic micelles have been used to study the effect of charge of proflavin on PET with amines. Magnetic field effect on PET reactions reveals that the parent spin-state of precursors of PET for DMA-PF + system is singlet while for DMDPM-PF + system is triplet, implying that the dynamics of PET is influenced by the structure of the donor.

Segmentation of mouse dynamic PET images using a multiphase level set method

NASA Astrophysics Data System (ADS)

Cheng-Liao, Jinxiu; Qi, Jinyi

2010-11-01

Image segmentation plays an important role in medical diagnosis. Here we propose an image segmentation method for four-dimensional mouse dynamic PET images. We consider that voxels inside each organ have similar time activity curves. The use of tracer dynamic information allows us to separate regions that have similar integrated activities in a static image but with different temporal responses. We develop a multiphase level set method that utilizes both the spatial and temporal information in a dynamic PET data set. Different weighting factors are assigned to each image frame based on the noise level and activity difference among organs of interest. We used a weighted absolute difference function in the data matching term to increase the robustness of the estimate and to avoid over-partition of regions with high contrast. We validated the proposed method using computer simulated dynamic PET data, as well as real mouse data from a microPET scanner, and compared the results with those of a dynamic clustering method. The results show that the proposed method results in smoother segments with the less number of misclassified voxels.

4D PET iterative deconvolution with spatiotemporal regularization for quantitative dynamic PET imaging.

PubMed

Reilhac, Anthonin; Charil, Arnaud; Wimberley, Catriona; Angelis, Georgios; Hamze, Hasar; Callaghan, Paul; Garcia, Marie-Paule; Boisson, Frederic; Ryder, Will; Meikle, Steven R; Gregoire, Marie-Claude

2015-09-01

Quantitative measurements in dynamic PET imaging are usually limited by the poor counting statistics particularly in short dynamic frames and by the low spatial resolution of the detection system, resulting in partial volume effects (PVEs). In this work, we present a fast and easy to implement method for the restoration of dynamic PET images that have suffered from both PVE and noise degradation. It is based on a weighted least squares iterative deconvolution approach of the dynamic PET image with spatial and temporal regularization. Using simulated dynamic [(11)C] Raclopride PET data with controlled biological variations in the striata between scans, we showed that the restoration method provides images which exhibit less noise and better contrast between emitting structures than the original images. In addition, the method is able to recover the true time activity curve in the striata region with an error below 3% while it was underestimated by more than 20% without correction. As a result, the method improves the accuracy and reduces the variability of the kinetic parameter estimates calculated from the corrected images. More importantly it increases the accuracy (from less than 66% to more than 95%) of measured biological variations as well as their statistical detectivity. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Modelling and simulation of [18F]fluoromisonidazole dynamics based on histology-derived microvessel maps

NASA Astrophysics Data System (ADS)

Mönnich, David; Troost, Esther G. C.; Kaanders, Johannes H. A. M.; Oyen, Wim J. G.; Alber, Markus; Thorwarth, Daniela

2011-04-01

Hypoxia can be assessed non-invasively by positron emission tomography (PET) using radiotracers such as [18F]fluoromisonidazole (Fmiso) accumulating in poorly oxygenated cells. Typical features of dynamic Fmiso PET data are high signal variability in the first hour after tracer administration and slow formation of a consistent contrast. The purpose of this study is to investigate whether these characteristics can be explained by the current conception of the underlying microscopic processes and to identify fundamental effects. This is achieved by modelling and simulating tissue oxygenation and tracer dynamics on the microscopic scale. In simulations, vessel structures on histology-derived maps act as sources and sinks for oxygen as well as tracer molecules. Molecular distributions in the extravascular space are determined by reaction-diffusion equations, which are solved numerically using a two-dimensional finite element method. Simulated Fmiso time activity curves (TACs), though not directly comparable to PET TACs, reproduce major characteristics of clinical curves, indicating that the microscopic model and the parameter values are adequate. Evidence for dependence of the early PET signal on the vascular fraction is found. Further, possible effects leading to late contrast formation and potential implications on the quantification of Fmiso PET data are discussed.

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT

PubMed Central

Puri, Tanuj; Siddique, Musib; Frost, Michelle L.; Moore, Amelia E. B.; Fogelman, Ignac

2018-01-01

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([18F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer. PMID:29541623

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

PubMed

Blake, Glen M; Puri, Tanuj; Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac

2018-02-01

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([ 18 F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [ 18 F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [ 18 F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [ 18 F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

Spectral Analysis of Dynamic PET Studies: A Review of 20 Years of Method Developments and Applications.

PubMed

Veronese, Mattia; Rizzo, Gaia; Bertoldo, Alessandra; Turkheimer, Federico E

2016-01-01

In Positron Emission Tomography (PET), spectral analysis (SA) allows the quantification of dynamic data by relating the radioactivity measured by the scanner in time to the underlying physiological processes of the system under investigation. Among the different approaches for the quantification of PET data, SA is based on the linear solution of the Laplace transform inversion whereas the measured arterial and tissue time-activity curves of a radiotracer are used to calculate the input response function of the tissue. In the recent years SA has been used with a large number of PET tracers in brain and nonbrain applications, demonstrating that it is a very flexible and robust method for PET data analysis. Differently from the most common PET quantification approaches that adopt standard nonlinear estimation of compartmental models or some linear simplifications, SA can be applied without defining any specific model configuration and has demonstrated very good sensitivity to the underlying kinetics. This characteristic makes it useful as an investigative tool especially for the analysis of novel PET tracers. The purpose of this work is to offer an overview of SA, to discuss advantages and limitations of the methodology, and to inform about its applications in the PET field.

Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft.

PubMed

Ukon, Naoyuki; Zhao, Songji; Yu, Wenwen; Shimizu, Yoichi; Nishijima, Ken-Ichi; Kubo, Naoki; Kitagawa, Yoshimasa; Tamaki, Nagara; Higashikawa, Kei; Yasui, Hironobu; Kuge, Yuji

2016-12-01

Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl- 3 H(N)]-3'-fluoro-3'-deoxythythymidine ([ 3 H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[ 18 F]fluoro-3'-deoxythymidine ([ 18 F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [ 18 F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [ 18 F]FLT. The dynamic pattern of [ 18 F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [ 18 F]FLT phosphorylation (k 3 ) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [ 18 F]FLT forward transport (K 1 ) to reverse transport (k 2 ), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic modeling could provide improved understanding of the biochemical processes involved in tumor responses to therapy.

Quantitative PET of liver functions

PubMed Central

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Quantitative PET of liver functions.

PubMed

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

High-resolution dynamic imaging and quantitative analysis of lung cancer xenografts in nude mice using clinical PET/CT

PubMed Central

Wang, Ying Yi; Wang, Kai; Xu, Zuo Yu; Song, Yan; Wang, Chu Nan; Zhang, Chong Qing; Sun, Xi Lin; Shen, Bao Zhong

2017-01-01

Considering the general application of dedicated small-animal positron emission tomography/computed tomography is limited, an acceptable alternative in many situations might be clinical PET/CT. To estimate the feasibility of using clinical PET/CT with [F-18]-fluoro-2-deoxy-D-glucose for high-resolution dynamic imaging and quantitative analysis of cancer xenografts in nude mice. Dynamic clinical PET/CT scans were performed on xenografts for 60 min after injection with [F-18]-fluoro-2-deoxy-D-glucose. Scans were reconstructed with or without SharpIR method in two phases. And mice were sacrificed to extracting major organs and tumors, using ex vivo γ-counting as a reference. Strikingly, we observed that the image quality and the correlation between the all quantitive data from clinical PET/CT and the ex vivo counting was better with the SharpIR reconstructions than without. Our data demonstrate that clinical PET/CT scanner with SharpIR reconstruction is a valuable tool for imaging small animals in preclinical cancer research, offering dynamic imaging parameters, good image quality and accurate data quatification. PMID:28881772

High-resolution dynamic imaging and quantitative analysis of lung cancer xenografts in nude mice using clinical PET/CT.

PubMed

Wang, Ying Yi; Wang, Kai; Xu, Zuo Yu; Song, Yan; Wang, Chu Nan; Zhang, Chong Qing; Sun, Xi Lin; Shen, Bao Zhong

2017-08-08

Considering the general application of dedicated small-animal positron emission tomography/computed tomography is limited, an acceptable alternative in many situations might be clinical PET/CT. To estimate the feasibility of using clinical PET/CT with [F-18]-fluoro-2-deoxy-D-glucose for high-resolution dynamic imaging and quantitative analysis of cancer xenografts in nude mice. Dynamic clinical PET/CT scans were performed on xenografts for 60 min after injection with [F-18]-fluoro-2-deoxy-D-glucose. Scans were reconstructed with or without SharpIR method in two phases. And mice were sacrificed to extracting major organs and tumors, using ex vivo γ-counting as a reference. Strikingly, we observed that the image quality and the correlation between the all quantitive data from clinical PET/CT and the ex vivo counting was better with the SharpIR reconstructions than without. Our data demonstrate that clinical PET/CT scanner with SharpIR reconstruction is a valuable tool for imaging small animals in preclinical cancer research, offering dynamic imaging parameters, good image quality and accurate data quatification.

Repurposing the Microsoft Kinect for Windows v2 for external head motion tracking for brain PET.

PubMed

Noonan, P J; Howard, J; Hallett, W A; Gunn, R N

2015-11-21

Medical imaging systems such as those used in positron emission tomography (PET) are capable of spatial resolutions that enable the imaging of small, functionally important brain structures. However, the quality of data from PET brain studies is often limited by subject motion during acquisition. This is particularly challenging for patients with neurological disorders or with dynamic research studies that can last 90 min or more. Restraining head movement during the scan does not eliminate motion entirely and can be unpleasant for the subject. Head motion can be detected and measured using a variety of techniques that either use the PET data itself or an external tracking system. Advances in computer vision arising from the video gaming industry could offer significant benefits when re-purposed for medical applications. A method for measuring rigid body type head motion using the Microsoft Kinect v2 is described with results presenting  ⩽0.5 mm spatial accuracy. Motion data is measured in real-time at 30 Hz using the KinectFusion algorithm. Non-rigid motion is detected using the residual alignment energy data of the KinectFusion algorithm allowing for unreliable motion to be discarded. Motion data is aligned to PET listmode data using injected pulse sequences into the PET/CT gantry allowing for correction of rigid body motion. Pilot data from a clinical dynamic PET/CT examination is shown.

Repurposing the Microsoft Kinect for Windows v2 for external head motion tracking for brain PET

NASA Astrophysics Data System (ADS)

Noonan, P. J.; Howard, J.; Hallett, W. A.; Gunn, R. N.

2015-11-01

Medical imaging systems such as those used in positron emission tomography (PET) are capable of spatial resolutions that enable the imaging of small, functionally important brain structures. However, the quality of data from PET brain studies is often limited by subject motion during acquisition. This is particularly challenging for patients with neurological disorders or with dynamic research studies that can last 90 min or more. Restraining head movement during the scan does not eliminate motion entirely and can be unpleasant for the subject. Head motion can be detected and measured using a variety of techniques that either use the PET data itself or an external tracking system. Advances in computer vision arising from the video gaming industry could offer significant benefits when re-purposed for medical applications. A method for measuring rigid body type head motion using the Microsoft Kinect v2 is described with results presenting  ⩽0.5 mm spatial accuracy. Motion data is measured in real-time at 30 Hz using the KinectFusion algorithm. Non-rigid motion is detected using the residual alignment energy data of the KinectFusion algorithm allowing for unreliable motion to be discarded. Motion data is aligned to PET listmode data using injected pulse sequences into the PET/CT gantry allowing for correction of rigid body motion. Pilot data from a clinical dynamic PET/CT examination is shown.

An experimental phantom study of the effect of gadolinium-based MR contrast agents on PET attenuation coefficients and PET quantification in PET-MR imaging: application to cardiac studies.

PubMed

O' Doherty, Jim; Schleyer, Paul

2017-12-01

Simultaneous cardiac perfusion studies are an increasing trend in PET-MR imaging. During dynamic PET imaging, the introduction of gadolinium-based MR contrast agents (GBCA) at high concentrations during a dual injection of GBCA and PET radiotracer may cause increased attenuation effects of the PET signal, and thus errors in quantification of PET images. We thus aimed to calculate the change in linear attenuation coefficient (LAC) of a mixture of PET radiotracer and increasing concentrations of GBCA in solution and furthermore, to investigate if this change in LAC produced a measurable effect on the image-based PET activity concentration when attenuation corrected by three different AC strategies. We performed simultaneous PET-MR imaging of a phantom in a static scenario using a fixed activity of 40 MBq [18 F]-NaF, water, and an increasing GBCA concentration from 0 to 66 mM (based on an assumed maximum possible concentration of GBCA in the left ventricle in a clinical study). This simulated a range of clinical concentrations of GBCA. We investigated two methods to calculate the LAC of the solution mixture at 511 keV: (1) a mathematical mixture rule and (2) CT imaging of each concentration step and subsequent conversion to LAC at 511 keV. This comparison showed that the ranges of LAC produced by both methods are equivalent with an increase in LAC of the mixed solution of approximately 2% over the range of 0-66 mM. We then employed three different attenuation correction methods to the PET data: (1) each PET scan at a specific millimolar concentration of GBCA corrected by its corresponding CT scan, (2) each PET scan corrected by a CT scan with no GBCA present (i.e., at 0 mM GBCA), and (3) a manually generated attenuation map, whereby all CT voxels in the phantom at 0 mM were replaced by LAC = 0.1 cm -1 . All attenuation correction methods (1-3) were accurate to the true measured activity concentration within 5%, and there were no trends in image-based activity concentrations upon increasing the GBCA concentration of the solution. The presence of high GBCA concentration (representing a worst-case scenario in dynamic cardiac studies) in solution with PET radiotracer produces a minimal effect on attenuation-corrected PET quantification.

Method of simulation and visualization of FDG metabolism based on VHP image

NASA Astrophysics Data System (ADS)

Cui, Yunfeng; Bai, Jing

2005-04-01

FDG ([18F] 2-fluoro-2-deoxy-D-glucose) is the typical tracer used in clinical PET (positron emission tomography) studies. The FDG-PET is an important imaging tool for early diagnosis and treatment of malignant tumor and functional disease. The main purpose of this work is to propose a method that represents FDG metabolism in human body through the simulation and visualization of 18F distribution process dynamically based on the segmented VHP (Visible Human Project) image dataset. First, the plasma time-activity curve (PTAC) and the tissues time-activity curves (TTAC) are obtained from the previous studies and the literatures. According to the obtained PTAC and TTACs, a set of corresponding values are assigned to the segmented VHP image, Thus a set of dynamic images are derived to show the 18F distribution in the concerned tissues for the predetermined sampling schedule. Finally, the simulated FDG distribution images are visualized in 3D and 2D formats, respectively, incorporated with principal interaction functions. As compared with original PET image, our visualization result presents higher resolution because of the high resolution of VHP image data, and show the distribution process of 18F dynamically. The results of our work can be used in education and related research as well as a tool for the PET operator to design their PET experiment program.

Dynamic PET image reconstruction integrating temporal regularization associated with respiratory motion correction for applications in oncology

NASA Astrophysics Data System (ADS)

Merlin, Thibaut; Visvikis, Dimitris; Fernandez, Philippe; Lamare, Frédéric

2018-02-01

Respiratory motion reduces both the qualitative and quantitative accuracy of PET images in oncology. This impact is more significant for quantitative applications based on kinetic modeling, where dynamic acquisitions are associated with limited statistics due to the necessity of enhanced temporal resolution. The aim of this study is to address these drawbacks, by combining a respiratory motion correction approach with temporal regularization in a unique reconstruction algorithm for dynamic PET imaging. Elastic transformation parameters for the motion correction are estimated from the non-attenuation-corrected PET images. The derived displacement matrices are subsequently used in a list-mode based OSEM reconstruction algorithm integrating a temporal regularization between the 3D dynamic PET frames, based on temporal basis functions. These functions are simultaneously estimated at each iteration, along with their relative coefficients for each image voxel. Quantitative evaluation has been performed using dynamic FDG PET/CT acquisitions of lung cancer patients acquired on a GE DRX system. The performance of the proposed method is compared with that of a standard multi-frame OSEM reconstruction algorithm. The proposed method achieved substantial improvements in terms of noise reduction while accounting for loss of contrast due to respiratory motion. Results on simulated data showed that the proposed 4D algorithms led to bias reduction values up to 40% in both tumor and blood regions for similar standard deviation levels, in comparison with a standard 3D reconstruction. Patlak parameter estimations on reconstructed images with the proposed reconstruction methods resulted in 30% and 40% bias reduction in the tumor and lung region respectively for the Patlak slope, and a 30% bias reduction for the intercept in the tumor region (a similar Patlak intercept was achieved in the lung area). Incorporation of the respiratory motion correction using an elastic model along with a temporal regularization in the reconstruction process of the PET dynamic series led to substantial quantitative improvements and motion artifact reduction. Future work will include the integration of a linear FDG kinetic model, in order to directly reconstruct parametric images.

Dynamic PET image reconstruction integrating temporal regularization associated with respiratory motion correction for applications in oncology.

PubMed

Merlin, Thibaut; Visvikis, Dimitris; Fernandez, Philippe; Lamare, Frédéric

2018-02-13

Respiratory motion reduces both the qualitative and quantitative accuracy of PET images in oncology. This impact is more significant for quantitative applications based on kinetic modeling, where dynamic acquisitions are associated with limited statistics due to the necessity of enhanced temporal resolution. The aim of this study is to address these drawbacks, by combining a respiratory motion correction approach with temporal regularization in a unique reconstruction algorithm for dynamic PET imaging. Elastic transformation parameters for the motion correction are estimated from the non-attenuation-corrected PET images. The derived displacement matrices are subsequently used in a list-mode based OSEM reconstruction algorithm integrating a temporal regularization between the 3D dynamic PET frames, based on temporal basis functions. These functions are simultaneously estimated at each iteration, along with their relative coefficients for each image voxel. Quantitative evaluation has been performed using dynamic FDG PET/CT acquisitions of lung cancer patients acquired on a GE DRX system. The performance of the proposed method is compared with that of a standard multi-frame OSEM reconstruction algorithm. The proposed method achieved substantial improvements in terms of noise reduction while accounting for loss of contrast due to respiratory motion. Results on simulated data showed that the proposed 4D algorithms led to bias reduction values up to 40% in both tumor and blood regions for similar standard deviation levels, in comparison with a standard 3D reconstruction. Patlak parameter estimations on reconstructed images with the proposed reconstruction methods resulted in 30% and 40% bias reduction in the tumor and lung region respectively for the Patlak slope, and a 30% bias reduction for the intercept in the tumor region (a similar Patlak intercept was achieved in the lung area). Incorporation of the respiratory motion correction using an elastic model along with a temporal regularization in the reconstruction process of the PET dynamic series led to substantial quantitative improvements and motion artifact reduction. Future work will include the integration of a linear FDG kinetic model, in order to directly reconstruct parametric images.

Impact of respiratory motion correction and spatial resolution on lesion detection in PET: a simulation study based on real MR dynamic data

NASA Astrophysics Data System (ADS)

Polycarpou, Irene; Tsoumpas, Charalampos; King, Andrew P.; Marsden, Paul K.

2014-02-01

The aim of this study is to investigate the impact of respiratory motion correction and spatial resolution on lesion detectability in PET as a function of lesion size and tracer uptake. Real respiratory signals describing different breathing types are combined with a motion model formed from real dynamic MR data to simulate multiple dynamic PET datasets acquired from a continuously moving subject. Lung and liver lesions were simulated with diameters ranging from 6 to 12 mm and lesion to background ratio ranging from 3:1 to 6:1. Projection data for 6 and 3 mm PET scanner resolution were generated using analytic simulations and reconstructed without and with motion correction. Motion correction was achieved using motion compensated image reconstruction. The detectability performance was quantified by a receiver operating characteristic (ROC) analysis obtained using a channelized Hotelling observer and the area under the ROC curve (AUC) was calculated as the figure of merit. The results indicate that respiratory motion limits the detectability of lung and liver lesions, depending on the variation of the breathing cycle length and amplitude. Patients with large quiescent periods had a greater AUC than patients with regular breathing cycles and patients with long-term variability in respiratory cycle or higher motion amplitude. In addition, small (less than 10 mm diameter) or low contrast (3:1) lesions showed the greatest improvement in AUC as a result of applying motion correction. In particular, after applying motion correction the AUC is improved by up to 42% with current PET resolution (i.e. 6 mm) and up to 51% for higher PET resolution (i.e. 3 mm). Finally, the benefit of increasing the scanner resolution is small unless motion correction is applied. This investigation indicates high impact of respiratory motion correction on lesion detectability in PET and highlights the importance of motion correction in order to benefit from the increased resolution of future PET scanners.

Improved quantitation and reproducibility in multi-PET/CT lung studies by combining CT information.

PubMed

Holman, Beverley F; Cuplov, Vesna; Millner, Lynn; Endozo, Raymond; Maher, Toby M; Groves, Ashley M; Hutton, Brian F; Thielemans, Kris

2018-06-05

Matched attenuation maps are vital for obtaining accurate and reproducible kinetic and static parameter estimates from PET data. With increased interest in PET/CT imaging of diffuse lung diseases for assessing disease progression and treatment effectiveness, understanding the extent of the effect of respiratory motion and establishing methods for correction are becoming more important. In a previous study, we have shown that using the wrong attenuation map leads to large errors due to density mismatches in the lung, especially in dynamic PET scans. Here, we extend this work to the case where the study is sub-divided into several scans, e.g. for patient comfort, each with its own CT (cine-CT and 'snap shot' CT). A method to combine multi-CT information into a combined-CT has then been developed, which averages the CT information from each study section to produce composite CT images with the lung density more representative of that in the PET data. This combined-CT was applied to nine patients with idiopathic pulmonary fibrosis, imaged with dynamic 18 F-FDG PET/CT to determine the improvement in the precision of the parameter estimates. Using XCAT simulations, errors in the influx rate constant were found to be as high as 60% in multi-PET/CT studies. Analysis of patient data identified displacements between study sections in the time activity curves, which led to an average standard error in the estimates of the influx rate constant of 53% with conventional methods. This reduced to within 5% after use of combined-CTs for attenuation correction of the study sections. Use of combined-CTs to reconstruct the sections of a multi-PET/CT study, as opposed to using the individually acquired CTs at each study stage, produces more precise parameter estimates and may improve discrimination between diseased and normal lung.

Dynamic-compliance and viscosity of PET and PEN

NASA Astrophysics Data System (ADS)

Weick, Brian L.

2016-05-01

Complex dynamic-compliance and in-phase dynamic-viscosity data are presented and analyzed for PET and PEN advanced polyester substrates used for magnetic tapes. Frequency-temperature superposition is used to predict long-term behavior. Temperature and frequency ranges for the primary glass transition and secondary transitions are discussed and compared for PET and PEN. Shift factors from frequency-temperature superposition are used to determine activation energies for the transitions, and WLF parameters are determined for the polyester substrates.

Dynamic-compliance and viscosity of PET and PEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weick, Brian L.

Complex dynamic-compliance and in-phase dynamic-viscosity data are presented and analyzed for PET and PEN advanced polyester substrates used for magnetic tapes. Frequency-temperature superposition is used to predict long-term behavior. Temperature and frequency ranges for the primary glass transition and secondary transitions are discussed and compared for PET and PEN. Shift factors from frequency-temperature superposition are used to determine activation energies for the transitions, and WLF parameters are determined for the polyester substrates.

Dynamic PET simulator via tomographic emission projection for kinetic modeling and parametric image studies.

PubMed

Häggström, Ida; Beattie, Bradley J; Schmidtlein, C Ross

2016-06-01

To develop and evaluate a fast and simple tool called dpetstep (Dynamic PET Simulator of Tracers via Emission Projection), for dynamic PET simulations as an alternative to Monte Carlo (MC), useful for educational purposes and evaluation of the effects of the clinical environment, postprocessing choices, etc., on dynamic and parametric images. The tool was developed in matlab using both new and previously reported modules of petstep (PET Simulator of Tracers via Emission Projection). Time activity curves are generated for each voxel of the input parametric image, whereby effects of imaging system blurring, counting noise, scatters, randoms, and attenuation are simulated for each frame. Each frame is then reconstructed into images according to the user specified method, settings, and corrections. Reconstructed images were compared to MC data, and simple Gaussian noised time activity curves (GAUSS). dpetstep was 8000 times faster than MC. Dynamic images from dpetstep had a root mean square error that was within 4% on average of that of MC images, whereas the GAUSS images were within 11%. The average bias in dpetstep and MC images was the same, while GAUSS differed by 3% points. Noise profiles in dpetstep images conformed well to MC images, confirmed visually by scatter plot histograms, and statistically by tumor region of interest histogram comparisons that showed no significant differences (p < 0.01). Compared to GAUSS, dpetstep images and noise properties agreed better with MC. The authors have developed a fast and easy one-stop solution for simulations of dynamic PET and parametric images, and demonstrated that it generates both images and subsequent parametric images with very similar noise properties to those of MC images, in a fraction of the time. They believe dpetstep to be very useful for generating fast, simple, and realistic results, however since it uses simple scatter and random models it may not be suitable for studies investigating these phenomena. dpetstep can be downloaded free of cost from https://github.com/CRossSchmidtlein/dPETSTEP.

Diagnostic performance of a streamlined 18F-choline PET-CT protocol for the detection of prostate carcinoma recurrence in combination with appropriate-use criteria.

PubMed

Frood, R; Baren, J; McDermott, G; Bottomley, D; Patel, C; Scarsbrook, A

2018-04-30

To evaluate the efficacy of single time-point half-body (skull base to thighs) fluorine-18 choline positron emission tomography-computed tomography (PET-CT) compared to a triple-phase acquisition protocol in the detection of prostate carcinoma recurrence. Consecutive choline PET-CT studies performed at a single tertiary referral centre in patients with biochemical recurrence of prostate carcinoma between September 2012 and March 2017 were reviewed retrospectively. The indication for the study, imaging protocol used, imaging findings, whether management was influenced by the PET-CT, and subsequent patient outcome were recorded. Ninety-one examinations were performed during the study period; 42 were carried out using a triple-phase protocol (dynamic pelvic imaging for 20 minutes after tracer injection, half-body acquisition at 60 minutes and delayed pelvic scan at 90 minutes) between 2012 and August 2015. Subsequently following interim review of diagnostic performance, a streamlined protocol and appropriate-use criteria were introduced. Forty-nine examinations were carried out using the single-phase protocol between 2015 and 2017. Twenty-nine (69%) of the triple-phase studies were positive for recurrence compared to 38 (78%) of the single-phase studies. Only one patient who had a single-phase study would have benefited from a dynamic acquisition, they have required no further treatment or imaging and are currently under prostate-specific antigen (PSA) surveillance. Choline PET-CT remains a useful tool for the detection of prostate recurrence when used in combination with appropriate-use criteria. Removal of dynamic and delayed acquisition phases reduces study time without adversely affecting accuracy. Benefits include shorter imaging time which improves patient comfort, reduced cost, and improved scanner efficiency. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A six-year longitudinal PET study of (+)-[11C]DTBZ binding to the VMAT2 in monkey brain.

PubMed

Kilbourn, Michael R; Koeppe, Robert A

2017-12-01

The longitudinal reproducibility of in vivo binding potential measures for [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ) binding to the vesicular monoamine transporter 2 (VMAT2) site in primate brain was examined using a unique dataset of repeated control PET imaging studies. Forty-one dynamic [ 11 C]DTBZ PET studies were completed in a single rhesus monkey. Imaging equipment (microPET P4), personnel, radiotracer characteristics (injected mass amounts, molar activity) and image data analysis (BP ND-Logan ) were consistent throughout the entire sequence of PET studies. Same day reproducibility of BP ND-Logan estimates of specific binding was very good (-3% and -7% changes) for two control-control sessions. Over the full 74 months, the average BP ND-Logan value for [ 11 C]DTBZ-PET studies was 4.19±0.52, for a variance of 12%. No age-dependent change in binding potentials was observed over the six-year period. If the technical variables associated with PET scanner are consistently maintained, including PET scanner, imaging procedures and radiotracer preparation, in vivo biochemistry can be reproducibly measured in the primate brain over a multi-year period of time. Copyright © 2017 Elsevier Inc. All rights reserved.

Direct Patlak Reconstruction From Dynamic PET Data Using the Kernel Method With MRI Information Based on Structural Similarity.

PubMed

Gong, Kuang; Cheng-Liao, Jinxiu; Wang, Guobao; Chen, Kevin T; Catana, Ciprian; Qi, Jinyi

2018-04-01

Positron emission tomography (PET) is a functional imaging modality widely used in oncology, cardiology, and neuroscience. It is highly sensitive, but suffers from relatively poor spatial resolution, as compared with anatomical imaging modalities, such as magnetic resonance imaging (MRI). With the recent development of combined PET/MR systems, we can improve the PET image quality by incorporating MR information into image reconstruction. Previously, kernel learning has been successfully embedded into static and dynamic PET image reconstruction using either PET temporal or MRI information. Here, we combine both PET temporal and MRI information adaptively to improve the quality of direct Patlak reconstruction. We examined different approaches to combine the PET and MRI information in kernel learning to address the issue of potential mismatches between MRI and PET signals. Computer simulations and hybrid real-patient data acquired on a simultaneous PET/MR scanner were used to evaluate the proposed methods. Results show that the method that combines PET temporal information and MRI spatial information adaptively based on the structure similarity index has the best performance in terms of noise reduction and resolution improvement.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; Warwitz, Boris; Scarpa, Lorenza; Roig, Llanos Geraldo; Kendler, Dorota; von Guggenberg, Elisabeth; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-05-01

PET/CT with 68 Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68 Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to 68 Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUV max of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68 Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suv max was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in 68 Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60 min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68 Ga-PSMA-11 PET/CT.

Acceleration of the direct reconstruction of linear parametric images using nested algorithms.

PubMed

Wang, Guobao; Qi, Jinyi

2010-03-07

Parametric imaging using dynamic positron emission tomography (PET) provides important information for biological research and clinical diagnosis. Indirect and direct methods have been developed for reconstructing linear parametric images from dynamic PET data. Indirect methods are relatively simple and easy to implement because the image reconstruction and kinetic modeling are performed in two separate steps. Direct methods estimate parametric images directly from raw PET data and are statistically more efficient. However, the convergence rate of direct algorithms can be slow due to the coupling between the reconstruction and kinetic modeling. Here we present two fast gradient-type algorithms for direct reconstruction of linear parametric images. The new algorithms decouple the reconstruction and linear parametric modeling at each iteration by employing the principle of optimization transfer. Convergence speed is accelerated by running more sub-iterations of linear parametric estimation because the computation cost of the linear parametric modeling is much less than that of the image reconstruction. Computer simulation studies demonstrated that the new algorithms converge much faster than the traditional expectation maximization (EM) and the preconditioned conjugate gradient algorithms for dynamic PET.

Myocardial perfusion imaging with PET

PubMed Central

Nakazato, Ryo; Berman, Daniel S; Alexanderson, Erick; Slomka, Piotr

2013-01-01

PET-myocardial perfusion imaging (MPI) allows accurate measurement of myocardial perfusion, absolute myocardial blood flow and function at stress and rest in a single study session performed in approximately 30 min. Various PET tracers are available for MPI, and rubidium-82 or nitrogen-13-ammonia is most commonly used. In addition, a new fluorine-18-based PET-MPI tracer is currently being evaluated. Relative quantification of PET perfusion images shows very high diagnostic accuracy for detection of obstructive coronary artery disease. Dynamic myocardial blood flow analysis has demonstrated additional prognostic value beyond relative perfusion imaging. Patient radiation dose can be reduced and image quality can be improved with latest advances in PET/CT equipment. Simultaneous assessment of both anatomy and perfusion by hybrid PET/CT can result in improved diagnostic accuracy. Compared with SPECT-MPI, PET-MPI provides higher diagnostic accuracy, using lower radiation doses during a shorter examination time period for the detection of coronary artery disease. PMID:23671459

Temporal Processing of Dynamic Positron Emission Tomography via Principal Component Analysis in the Sinogram Domain

NASA Astrophysics Data System (ADS)

Chen, Zhe; Parker, B. J.; Feng, D. D.; Fulton, R.

2004-10-01

In this paper, we compare various temporal analysis schemes applied to dynamic PET for improved quantification, image quality and temporal compression purposes. We compare an optimal sampling schedule (OSS) design, principal component analysis (PCA) applied in the image domain, and principal component analysis applied in the sinogram domain; for region-of-interest quantification, sinogram-domain PCA is combined with the Huesman algorithm to quantify from the sinograms directly without requiring reconstruction of all PCA channels. Using a simulated phantom FDG brain study and three clinical studies, we evaluate the fidelity of the compressed data for estimation of local cerebral metabolic rate of glucose by a four-compartment model. Our results show that using a noise-normalized PCA in the sinogram domain gives similar compression ratio and quantitative accuracy to OSS, but with substantially better precision. These results indicate that sinogram-domain PCA for dynamic PET can be a useful preprocessing stage for PET compression and quantification applications.

Role of FDG-PET/MRI, FDG-PET/CT, and Dynamic Susceptibility Contrast Perfusion MRI in Differentiating Radiation Necrosis from Tumor Recurrence in Glioblastomas.

PubMed

Hojjati, Mojgan; Badve, Chaitra; Garg, Vasant; Tatsuoka, Curtis; Rogers, Lisa; Sloan, Andrew; Faulhaber, Peter; Ros, Pablo R; Wolansky, Leo J

2018-01-01

To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination. Additionally, 19 of 24 patients underwent PET/CT on the same day. Diagnosis was established by pathology in 17 of 24 and by clinical/radiologic consensus in 7 of 24. For the quantitative PET/MRI and PET/CT analysis, a region of interest (ROI) was drawn around each lesion and within the contralateral white matter. Lesion to contralateral white matter ratios for relative maximum, mean, and median were calculated. For pMRI, lesion ROI was drawn on the cerebral blood volume (CBV) maps and histogram metrics were calculated. Diagnostic performance for each metric was assessed using receiver operating characteristic curve analysis and area under curve (AUC) was calculated. In 24 patients, 28 lesions were identified. For PET/MRI, relative mean ≥ 1.31 resulted in AUC of .94 with both sensitivity and negative predictive values (NPVs) of 100%. For pMRI, CBV max ≥3.32 yielded an AUC of .94 with both sensitivity and NPV measuring 100%. The joint model utilizing r-mean (PET/MRI) and CBV mode (pMRI) resulted in AUC of 1.0. Our study demonstrates that quantitative PET/MRI parameters in combination with DSC pMRI provide the best diagnostic utility in distinguishing RN from TR in treated GBMs. © 2017 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model.

PubMed

Hardiansyah, Deni; Attarwala, Ali Asgar; Kletting, Peter; Mottaghy, Felix M; Glatting, Gerhard

2017-10-01

To investigate the accuracy of predicted time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK) model. PBPK parameters were estimated using biokinetic data of 15 patients after injection of (152±15)MBq of 111 In-DTPAOC (total peptide amount (5.78±0.25)nmol). True mathematical phantoms of patients (MPPs) were the PBPK model with the estimated parameters. Dynamic PET measurements were simulated as being done after bolus injection of 150MBq 68 Ga-DOTATATE using the true MPPs. Dynamic PET scans around 35min p.i. (P 1 ), 4h p.i. (P 2 ) and the combination of P 1 and P 2 (P 3 ) were simulated. Each measurement was simulated with four frames of 5min each and 2 bed positions. PBPK parameters were fitted to the PET data to derive the PET-predicted MPPs. Therapy was simulated assuming an infusion of 5.1GBq of 90 Y-DOTATATE over 30min in both true and PET-predicted MPPs. TIACs of simulated therapy were calculated, true MPPs (true TIACs) and predicted MPPs (predicted TIACs) followed by the calculation of variabilities v. For P 1 and P 2 the population variabilities of kidneys, liver and spleen were acceptable (v<10%). For the tumours and the remainders, the values were large (up to 25%). For P 3 , population variabilities for all organs including the remainder further improved, except that of the tumour (v>10%). Treatment planning of PRRT based on dynamic PET data seems possible for the kidneys, liver and spleen using a PBPK model and patient specific information. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

(68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer.

PubMed

Sachpekidis, C; Eder, M; Kopka, K; Mier, W; Hadaschik, B A; Haberkorn, U; Dimitrakopoulou-Strauss, A

2016-07-01

We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand (68)Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and (68)Ga-PSMA-11 PET parameters is also investigated. 31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0 years) were enrolled in the analysis. The median PSA value was 2.0 ng/mL (range = 0.1 - 130.0 ng/mL) and the median Gleason score was 7 (range = 5 - 9). 8/31 (25.8 %) of the included patients had a PSA value < 0.5 ng/ml. All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with (68)Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). 22/31 patients (71.0 %) were (68)Ga-PSMA-11-positive, while 9/31 (29.0 %) patients were (68)Ga-PSMA-11-negative. The median PSA value in the (68)Ga-PSMA-11-positive group was significantly higher (median = 2.35 ng/mL; range = 0.19 - 130.0 ng/mL) than in the (68)Ga-PSMA-11-negative group (median value: 0.34 ng/mL; range = 0.10 - 4.20 ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUVaverage = 12.4 (median = 9.0; range = 2.2 - 84.5) and mean SUVmax = 18.8 (median = 14.1; range = 3.1 - 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K1 = 0.26, k3 = 0.30, influx = 0.14 and FD = 1.24. Time-activity curves derived from PC-recurrence indicative lesions revealed an increasing (68)Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant, correlation between PSA levels and the number of lesions detected on (68)Ga-PSMA-11 PET/CT (r = 0.54) and between PSA levels and SUVaverage (r = 0.48) or SUVmax (r = 0.44). Ga-PSMA-11 PET/CT demonstrated an overall detection rate of 71.0 % 60 min p.i. of the radiotracer in a mixed patient population with respect to PSA levels and including patients with very low PSA values. Higher PSA values were associated with a higher detection rate. The tracer uptake in PC-recurrence-indicative lesions is increasing during the 60 minutes of dynamic PET acquisition.

First validation of myocardial flow reserve assessed by dynamic 99mTc-sestamibi CZT-SPECT camera: head to head comparison with 15O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study.

PubMed

Agostini, Denis; Roule, Vincent; Nganoa, Catherine; Roth, Nathaniel; Baavour, Raphael; Parienti, Jean-Jacques; Beygui, Farzin; Manrique, Alain

2018-07-01

We assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with 15 O-water PET and fractional flow reserve (FFR). Thirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress 99m Tc-sestamibi CZT-SPECT and 15 O-water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively. CZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR ≤ 0.8). Dynamic 99m Tc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to 15 O-water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD.

Dynamic 68Ga-DOTATOC PET/CT and static image in NET patients. Correlation of parameters during PRRT.

PubMed

Van Binnebeek, Sofie; Koole, Michel; Terwinghe, Christelle; Baete, Kristof; Vanbilloen, Bert; Haustermans, Karine; Clement, Paul M; Bogaerts, Kris; Verbruggen, Alfons; Nackaerts, Kris; Van Cutsem, Eric; Verslype, Chris; Mottaghy, Felix M; Deroose, Christophe M

2016-06-28

To investigate the relationship between the dynamic parameters (Ki) and static image-derived parameters of 68Ga-DOTATOC-PET, to determine which static parameter best reflects underlying somatostatin-receptor-expression (SSR) levels on neuroendocrine tumours (NETs). 20 patients with metastasized NETs underwent a dynamic and static 68Ga-DOTATOC-PET before PRRT and at 7 and 40 weeks after the first administration of 90Y-DOTATOC (in total 4 cycles were planned); 175 lesions were defined and analyzed on the dynamic as well as static scans. Quantitative analysis was performed using the software PMOD. One to five target lesions per patient were chosen and delineated manually on the baseline dynamic scan and further, on the corresponding static 68Ga-DOTATOC-PET and the dynamic and static 68Ga-DOTATOC-PET at the other time-points; SUVmax and SUVmean of the lesions was assessed on the other six scans. The input function was retrieved from the abdominal aorta on the images. Further on, Ki was calculated using the Patlak-Plot. At last, 5 reference regions for normalization of SUVtumour were delineated on the static scans resulting in 5 ratios (SUVratio). SUVmax and SUVmean of the tumoural lesions on the dynamic 68Ga-DOTATOC-PET had a very strong correlation with the corresponding parameters in the static scan (R²: 0.94 and 0.95 respectively). SUVmax, SUVmean and Ki of the lesions showed a good linear correlation; the SUVratios correlated poorly with Ki. A significantly better correlation was noticed between Ki and SUVtumour(max and mean) (p < 0.0001). As the dynamic parameter Ki correlates best with the absolute SUVtumour, SUVtumour best reflects underlying SSR-levels in NETs.

Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

PubMed

Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

2015-01-01

Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.

PubMed

Guo, Ning; Zhang, Fan; Zhang, Xiaomeng; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O; Niu, Gang; Li, Quanzheng; Chen, Xiaoyuan

2015-12-01

The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [(18)F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [(18)F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p < 0.05), and the difference was more significant at day 3 (p < 0.01), compared with the control group. However, the tracer uptake (%ID/g) derived from static images at 1-h time point did not show significant difference between the treated and control tumors until day 3. Little difference in tracer uptake (%ID/g) or BPND was found between treated and control A549 tumors. Considering the tracer retention in tumor and the slower clearance due to damaged tumor vasculature after treatment, BPND representing the actual specific binding portion appears to be more sensitive and accurate than the semiquantitative parameters (such as %ID/g) derived from static images to assess the early response of tumor to VDA treatment. Quantitative analysis based on dynamic PET with [(18)F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.

Validation of a Multimodality Flow Phantom and Its Application for Assessment of Dynamic SPECT and PET Technologies.

PubMed

Gabrani-Juma, Hanif; Clarkin, Owen J; Pourmoghaddas, Amir; Driscoll, Brandon; Wells, R Glenn; deKemp, Robert A; Klein, Ran

2017-01-01

Simple and robust techniques are lacking to assess performance of flow quantification using dynamic imaging. We therefore developed a method to qualify flow quantification technologies using a physical compartment exchange phantom and image analysis tool. We validate and demonstrate utility of this method using dynamic PET and SPECT. Dynamic image sequences were acquired on two PET/CT and a cardiac dedicated SPECT (with and without attenuation and scatter corrections) systems. A two-compartment exchange model was fit to image derived time-activity curves to quantify flow rates. Flowmeter measured flow rates (20-300 mL/min) were set prior to imaging and were used as reference truth to which image derived flow rates were compared. Both PET cameras had excellent agreement with truth ( [Formula: see text]). High-end PET had no significant bias (p > 0.05) while lower-end PET had minimal slope bias (wash-in and wash-out slopes were 1.02 and 1.01) but no significant reduction in precision relative to high-end PET (<15% vs. <14% limits of agreement, p > 0.3). SPECT (without scatter and attenuation corrections) slope biases were noted (0.85 and 1.32) and attributed to camera saturation in early time frames. Analysis of wash-out rates from non-saturated, late time frames resulted in excellent agreement with truth ( [Formula: see text], slope = 0.97). Attenuation and scatter corrections did not significantly impact SPECT performance. The proposed phantom, software and quality assurance paradigm can be used to qualify imaging instrumentation and protocols for quantification of kinetic rate parameters using dynamic imaging.

Towards quantitative PET/MRI: a review of MR-based attenuation correction techniques.

PubMed

Hofmann, Matthias; Pichler, Bernd; Schölkopf, Bernhard; Beyer, Thomas

2009-03-01

Positron emission tomography (PET) is a fully quantitative technology for imaging metabolic pathways and dynamic processes in vivo. Attenuation correction of raw PET data is a prerequisite for quantification and is typically based on separate transmission measurements. In PET/CT attenuation correction, however, is performed routinely based on the available CT transmission data. Recently, combined PET/magnetic resonance (MR) has been proposed as a viable alternative to PET/CT. Current concepts of PET/MRI do not include CT-like transmission sources and, therefore, alternative methods of PET attenuation correction must be found. This article reviews existing approaches to MR-based attenuation correction (MR-AC). Most groups have proposed MR-AC algorithms for brain PET studies and more recently also for torso PET/MR imaging. Most MR-AC strategies require the use of complementary MR and transmission images, or morphology templates generated from transmission images. We review and discuss these algorithms and point out challenges for using MR-AC in clinical routine. MR-AC is work-in-progress with potentially promising results from a template-based approach applicable to both brain and torso imaging. While efforts are ongoing in making clinically viable MR-AC fully automatic, further studies are required to realize the potential benefits of MR-based motion compensation and partial volume correction of the PET data.

VOXEL-LEVEL MAPPING OF TRACER KINETICS IN PET STUDIES: A STATISTICAL APPROACH EMPHASIZING TISSUE LIFE TABLES.

PubMed

O'Sullivan, Finbarr; Muzi, Mark; Mankoff, David A; Eary, Janet F; Spence, Alexander M; Krohn, Kenneth A

2014-06-01

Most radiotracers used in dynamic positron emission tomography (PET) scanning act in a linear time-invariant fashion so that the measured time-course data are a convolution between the time course of the tracer in the arterial supply and the local tissue impulse response, known as the tissue residue function. In statistical terms the residue is a life table for the transit time of injected radiotracer atoms. The residue provides a description of the tracer kinetic information measurable by a dynamic PET scan. Decomposition of the residue function allows separation of rapid vascular kinetics from slower blood-tissue exchanges and tissue retention. For voxel-level analysis, we propose that residues be modeled by mixtures of nonparametrically derived basis residues obtained by segmentation of the full data volume. Spatial and temporal aspects of diagnostics associated with voxel-level model fitting are emphasized. Illustrative examples, some involving cancer imaging studies, are presented. Data from cerebral PET scanning with 18 F fluoro-deoxyglucose (FDG) and 15 O water (H2O) in normal subjects is used to evaluate the approach. Cross-validation is used to make regional comparisons between residues estimated using adaptive mixture models with more conventional compartmental modeling techniques. Simulations studies are used to theoretically examine mean square error performance and to explore the benefit of voxel-level analysis when the primary interest is a statistical summary of regional kinetics. The work highlights the contribution that multivariate analysis tools and life-table concepts can make in the recovery of local metabolic information from dynamic PET studies, particularly ones in which the assumptions of compartmental-like models, with residues that are sums of exponentials, might not be certain.

Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging.

PubMed

Schmuck, Sebastian; Mamach, Martin; Wilke, Florian; von Klot, Christoph A; Henkenberens, Christoph; Thackeray, James T; Sohns, Jan M; Geworski, Lilli; Ross, Tobias L; Wester, Hans-Juergen; Christiansen, Hans; Bengel, Frank M; Derlin, Thorsten

2017-06-01

The aims of this study were to gain mechanistic insights into prostate cancer biology using dynamic imaging and to evaluate the usefulness of multiple time-point Ga-prostate-specific membrane antigen (PSMA) I&T PET/CT for the assessment of primary prostate cancer before prostatectomy. Twenty patients with prostate cancer underwent Ga-PSMA I&T PET/CT before prostatectomy. The PET protocol consisted of early dynamic pelvic imaging, followed by static scans at 60 and 180 minutes postinjection (p.i.). SUVs, time-activity curves, quantitative analysis based on a 2-tissue compartment model, Patlak analysis, histopathology, and Gleason grading were compared between prostate cancer and benign prostate gland. Primary tumors were identified on both early dynamic and delayed imaging in 95% of patients. Tracer uptake was significantly higher in prostate cancer compared with benign prostate tissue at any time point (P ≤ 0.0003) and increased over time. Consequently, the tumor-to-nontumor ratio within the prostate gland improved over time (2.8 at 10 minutes vs 17.1 at 180 minutes p.i.). Tracer uptake at both 60 and 180 minutes p.i. was significantly higher in patients with higher Gleason scores (P < 0.01). The influx rate (Ki) was higher in prostate cancer than in reference prostate gland (0.055 [r = 0.998] vs 0.017 [r = 0.996]). Primary prostate cancer is readily identified on early dynamic and static delayed Ga-PSMA ligand PET images. The tumor-to-nontumor ratio in the prostate gland improves over time, supporting a role of delayed imaging for optimal visualization of prostate cancer.

The use of multiple time point dynamic positron emission tomography/computed tomography in patients with oral/head and neck cancer does not predictably identify metastatic cervical lymph nodes.

PubMed

Carlson, Eric R; Schaefferkoetter, Josh; Townsend, David; McCoy, J Michael; Campbell, Paul D; Long, Misty

2013-01-01

To determine whether the time course of 18-fluorine fluorodeoxyglucose (18F-FDG) activity in multiple consecutively obtained 18F-FDG positron emission tomography (PET)/computed tomography (CT) scans predictably identifies metastatic cervical adenopathy in patients with oral/head and neck cancer. It is hypothesized that the activity will increase significantly over time only in those lymph nodes harboring metastatic cancer. A prospective cohort study was performed whereby patients with oral/head and neck cancer underwent consecutive imaging at 9 time points with PET/CT from 60 to 115 minutes after injection with (18)F-FDG. The primary predictor variable was the status of the lymph nodes based on dynamic PET/CT imaging. Metastatic lymph nodes were defined as those that showed an increase greater than or equal to 10% over the baseline standard uptake values. The primary outcome variable was the pathologic status of the lymph node. A total of 2,237 lymph nodes were evaluated histopathologically in the 83 neck dissections that were performed in 74 patients. A total of 119 lymph nodes were noted to have hypermetabolic activity on the 90-minute (static) portion of the study and were able to be assessed by time points. When we compared the PET/CT time point (dynamic) data with the histopathologic analysis of the lymph nodes, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 60.3%, 70.5%, 66.0%, 65.2%, and 65.5%, respectively. The use of dynamic PET/CT imaging does not permit the ablative surgeon to depend only on the results of the PET/CT study to determine which patients will benefit from neck dissection. As such, we maintain that surgeons should continue to rely on clinical judgment and maintain a low threshold for executing neck dissection in patients with oral/head and neck cancer, including those patients with N0 neck designations. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

First experience with early dynamic (18)F-NaF-PET/CT in patients with chronic osteomyelitis.

PubMed

Freesmeyer, Martin; Stecker, Franz F; Schierz, Jan-Henning; Hofmann, Gunther O; Winkens, Thomas

2014-05-01

This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using (18)F-sodium fluoride-((18)F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed(18)F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late (18)F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late (18)F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed(18)F-NaF -PET offers additional information about early radiotracer distribution to standard (18)F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed(18)F-NaF-PET to a three-phase bone scan.

Direct Parametric Reconstruction With Joint Motion Estimation/Correction for Dynamic Brain PET Data.

PubMed

Jiao, Jieqing; Bousse, Alexandre; Thielemans, Kris; Burgos, Ninon; Weston, Philip S J; Schott, Jonathan M; Atkinson, David; Arridge, Simon R; Hutton, Brian F; Markiewicz, Pawel; Ourselin, Sebastien

2017-01-01

Direct reconstruction of parametric images from raw photon counts has been shown to improve the quantitative analysis of dynamic positron emission tomography (PET) data. However it suffers from subject motion which is inevitable during the typical acquisition time of 1-2 hours. In this work we propose a framework to jointly estimate subject head motion and reconstruct the motion-corrected parametric images directly from raw PET data, so that the effects of distorted tissue-to-voxel mapping due to subject motion can be reduced in reconstructing the parametric images with motion-compensated attenuation correction and spatially aligned temporal PET data. The proposed approach is formulated within the maximum likelihood framework, and efficient solutions are derived for estimating subject motion and kinetic parameters from raw PET photon count data. Results from evaluations on simulated [ 11 C]raclopride data using the Zubal brain phantom and real clinical [ 18 F]florbetapir data of a patient with Alzheimer's disease show that the proposed joint direct parametric reconstruction motion correction approach can improve the accuracy of quantifying dynamic PET data with large subject motion.

(18)F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate.

PubMed

Sachpekidis, Christos; Mai, Elias K; Goldschmidt, Hartmut; Hillengass, Jens; Hose, Dirk; Pan, Leyun; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-06-01

The value of F-FDG PET in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the kinetics of F-FDG in the bone marrow and extramedullary sites in MM. This study aimed to evaluate quantitative data on kinetics and distribution patterns of F-FDG in MM patients with regard to pelvic bone marrow plasma cell infiltration. The study included 40 patients with primary MM. Dynamic PET/CT scanning of the lower lumbar spine and pelvis was performed after the administration of F-FDG. Whole-body PET/CT studies were performed. Sites of focal increased tracer uptake were considered as highly suggestive of myelomatous involvement after taking into account the patient history and CT findings. Bone marrow of the os ilium without pathologic tracer accumulation served as reference. The evaluation of dynamic PET/CT studies was based in addition to the conventional visual (qualitative) assessment, on semiquantitative (SUV) calculations, as well as on absolute quantitative estimations after application of a 2-tissue compartment model and a noncompartmental approach. F-FDG quantitative information and corresponding distribution patterns were correlated with pelvic bone marrow plasma cell infiltration. Fifty-two myelomatous lesions were detected in the pelvis. All parameters in suspected MM lesions ranged in significantly higher levels than in reference tissue (P < 0.01). Correlative analyses revealed that bone marrow plasma cell infiltration rate correlated significantly with SUVaverage, SUVmax, and the parameters K1, influx, and fractal dimension of F-FDG in reference bone marrow (P < 0.01). In addition, whole-body static PET/CT imaging demonstrated 4 patterns of tracer uptake; these are as follows: negative, focal, diffuse, and mixed (focal/diffuse) tracer uptake. Patients with a mixed pattern of radiotracer uptake had the highest mean plasma cell infiltration rate in their bone marrow, whereas those with negative PET/CT scans demonstrated the lowest bone marrow plasma cell infiltration. In total, 265 focal myeloma-indicative F-FDG-avid lesions were detected, 129 of which correlated with low-dose CT osteolytic findings. No significant correlation between the number of focal lesions detected in PET/CT and bone marrow infiltration was detected. The F-FDG kinetic parameters K1, influx, and fractal dimension as well as SUVaverage from reference tissue correlated significantly with bone marrow malignant plasma cell infiltration rate. Patients with negative PET/CT demonstrated the lowest bone marrow infiltration by malignant plasma cells, whereas those with a mixed pattern of tracer uptake had the highest infiltration.

Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

PubMed

Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

2018-05-01

Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

Simultaneous trimodal PET-MR-EEG imaging: Do EEG caps generate artefacts in PET images?

PubMed

Rajkumar, Ravichandran; Rota Kops, Elena; Mauler, Jörg; Tellmann, Lutz; Lerche, Christoph; Herzog, Hans; Shah, N Jon; Neuner, Irene

2017-01-01

Trimodal simultaneous acquisition of positron emission tomography (PET), magnetic resonance imaging (MRI), and electroencephalography (EEG) has become feasible due to the development of hybrid PET-MR scanners. To capture the temporal dynamics of neuronal activation on a millisecond-by-millisecond basis, an EEG system is appended to the quantitative high resolution PET-MR imaging modality already established in our institute. One of the major difficulties associated with the development of simultaneous trimodal acquisition is that the components traditionally used in each modality can cause interferences in its counterpart. The mutual interferences of MRI components and PET components on PET and MR images, and the influence of EEG electrodes on functional MRI images have been studied and reported on. Building on this, this study aims to investigate the influence of the EEG cap on the quality and quantification of PET images acquired during simultaneous PET-MR measurements. A preliminary transmission scan study on the ECAT HR+ scanner, using an Iida phantom, showed visible attenuation effect due to the EEG cap. The BrainPET-MR emission images of the Iida phantom with [18F]Fluordeoxyglucose, as well as of human subjects with the EEG cap, did not show significant effects of the EEG cap, even though the applied attenuation correction did not take into account the attenuation of the EEG cap itself.

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma

PubMed Central

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUVaverage for MM lesions was 11.9 and mean SUVmax was 23.2. Respectively, SUVaverage and SUVmax for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18F-NaF revealed the following mean values for MM lesions: K1 = 0.248 (1/min), k3 = 0.359 (1/min), influx (Ki) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K1 = 0.169 (1/min), k3 = 0.422 (1/min), influx (Ki) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUVaverage, SUVmax, K1, k3 and influx (Ki) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18F-NaF PET/CT in the diagnostic workup of MM. PMID:28913153

Dynamic PET simulator via tomographic emission projection for kinetic modeling and parametric image studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Häggström, Ida, E-mail: haeggsti@mskcc.org; Beattie, Bradley J.; Schmidtlein, C. Ross

2016-06-15

Purpose: To develop and evaluate a fast and simple tool called dPETSTEP (Dynamic PET Simulator of Tracers via Emission Projection), for dynamic PET simulations as an alternative to Monte Carlo (MC), useful for educational purposes and evaluation of the effects of the clinical environment, postprocessing choices, etc., on dynamic and parametric images. Methods: The tool was developed in MATLAB using both new and previously reported modules of PETSTEP (PET Simulator of Tracers via Emission Projection). Time activity curves are generated for each voxel of the input parametric image, whereby effects of imaging system blurring, counting noise, scatters, randoms, and attenuationmore » are simulated for each frame. Each frame is then reconstructed into images according to the user specified method, settings, and corrections. Reconstructed images were compared to MC data, and simple Gaussian noised time activity curves (GAUSS). Results: dPETSTEP was 8000 times faster than MC. Dynamic images from dPETSTEP had a root mean square error that was within 4% on average of that of MC images, whereas the GAUSS images were within 11%. The average bias in dPETSTEP and MC images was the same, while GAUSS differed by 3% points. Noise profiles in dPETSTEP images conformed well to MC images, confirmed visually by scatter plot histograms, and statistically by tumor region of interest histogram comparisons that showed no significant differences (p < 0.01). Compared to GAUSS, dPETSTEP images and noise properties agreed better with MC. Conclusions: The authors have developed a fast and easy one-stop solution for simulations of dynamic PET and parametric images, and demonstrated that it generates both images and subsequent parametric images with very similar noise properties to those of MC images, in a fraction of the time. They believe dPETSTEP to be very useful for generating fast, simple, and realistic results, however since it uses simple scatter and random models it may not be suitable for studies investigating these phenomena. dPETSTEP can be downloaded free of cost from https://github.com/CRossSchmidtlein/dPETSTEP.« less

Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability.

PubMed

Umile, Eric M; Sandel, M Elizabeth; Alavi, Abass; Terry, Charles M; Plotkin, Rosette C

2002-11-01

To determine whether patients with mild traumatic brain injury (TBI) and persistent postconcussive symptoms have evidence of temporal lobe injury on dynamic imaging. Case series. An academic medical center. Twenty patients with a clinical diagnosis of mild TBI and persistent postconcussive symptoms were referred for neuropsychologic evaluation and dynamic imaging. Fifteen (75%) had normal magnetic resonance imaging (MRI) and/or computed tomography (CT) scans at the time of injury. Neuropsychologic testing, positron-emission tomography (PET), and single-photon emission-computed tomography (SPECT). Temporal lobe findings on static imaging (MRI, CT) and dynamic imaging (PET, SPECT); neuropsychologic test findings on measures of verbal and visual memory. Testing documented neurobehavioral deficits in 19 patients (95%). Dynamic imaging documented abnormal findings in 18 patients (90%). Fifteen patients (75%) had temporal lobe abnormalities on PET and SPECT (primarily in medial temporal regions); abnormal findings were bilateral in 10 patients (50%) and unilateral in 5 (25%). Six patients (30%) had frontal abnormalities, and 8 (40%) had nonfrontotemporal abnormalities. Correlations between neuropsychologic testing and dynamic imaging could be established but not consistently across the whole group. Patients with mild TBI and persistent postconcussive symptoms have a high incidence of temporal lobe injury (presumably involving the hippocampus and related structures), which may explain the frequent finding of memory disorders in this population. The abnormal temporal lobe findings on PET and SPECT in humans may be analogous to the neuropathologic evidence of medial temporal injury provided by animal studies after mild TBI. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Characterization of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][Tf2N])∕TX-100∕cyclohexane ternary microemulsion: investigation of photoinduced electron transfer in this RTIL containing microemulsion.

PubMed

Sarkar, Souravi; Pramanik, Rajib; Ghatak, Chiranjib; Rao, Vishal Govind; Sarkar, Nilmoni

2011-02-21

In this study we have characterized a ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethyl- sulfonyl)imide containing ternary nonaqueous microemulsion ([Emim][Tf(2)N]∕∕TX-100∕cyclo- hexane). The phase behavior and dynamic light scattering study show that the [Emim][Tf(2)N]∕TX-100∕cyclohexane three component system can form microemulsion with [Emim][Tf(2)N] as polar core at suitable condition. We have investigated photoinduced electron transfer (PET) using dimethyl aniline as electron donor and several Coumarin dyes as electron acceptor molecules at two different R values (R = [ionic liquid]∕[surfactant]) to observe how the dynamics of the PET rate is affected in this type of confined microenvironment compared to that of the PET dynamics in neat ionic liquid and other pure solvent media. The plot of observed k(q) values with the free energy change (ΔG(0)) for electron transfer reaction shows an apparent inversion in the observed rate as predicted by the Marcus theory.

Poster — Thur Eve — 44: Linearization of Compartmental Models for More Robust Estimates of Regional Hemodynamic, Metabolic and Functional Parameters using DCE-CT/PET Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blais, AR; Dekaban, M; Lee, T-Y

2014-08-15

Quantitative analysis of dynamic positron emission tomography (PET) data usually involves minimizing a cost function with nonlinear regression, wherein the choice of starting parameter values and the presence of local minima affect the bias and variability of the estimated kinetic parameters. These nonlinear methods can also require lengthy computation time, making them unsuitable for use in clinical settings. Kinetic modeling of PET aims to estimate the rate parameter k{sub 3}, which is the binding affinity of the tracer to a biological process of interest and is highly susceptible to noise inherent in PET image acquisition. We have developed linearized kineticmore » models for kinetic analysis of dynamic contrast enhanced computed tomography (DCE-CT)/PET imaging, including a 2-compartment model for DCE-CT and a 3-compartment model for PET. Use of kinetic parameters estimated from DCE-CT can stabilize the kinetic analysis of dynamic PET data, allowing for more robust estimation of k{sub 3}. Furthermore, these linearized models are solved with a non-negative least squares algorithm and together they provide other advantages including: 1) only one possible solution and they do not require a choice of starting parameter values, 2) parameter estimates are comparable in accuracy to those from nonlinear models, 3) significantly reduced computational time. Our simulated data show that when blood volume and permeability are estimated with DCE-CT, the bias of k{sub 3} estimation with our linearized model is 1.97 ± 38.5% for 1,000 runs with a signal-to-noise ratio of 10. In summary, we have developed a computationally efficient technique for accurate estimation of k{sub 3} from noisy dynamic PET data.« less

Integrated analysis of dynamic FET PET/CT parameters, histology, and methylation profiling of 44 gliomas.

PubMed

Röhrich, Manuel; Huang, Kristin; Schrimpf, Daniel; Albert, Nathalie L; Hielscher, Thomas; von Deimling, Andreas; Schüller, Ulrich; Dimitrakopoulou-Strauss, Antonia; Haberkorn, Uwe

2018-05-07

Dynamic 18 F-FET PET/CT is a powerful tool for the diagnosis of gliomas. 18 F-FET PET time-activity curves (TAC) allow differentiation between histological low-grade gliomas (LGG) and high-grade gliomas (HGG). Molecular methods such as epigenetic profiling are of rising importance for glioma grading and subclassification. Here, we analysed dynamic 18 F-FET PET data, and the histological and epigenetic features of 44 gliomas. Dynamic 18 F-FET PET was performed in 44 patients with newly diagnosed, untreated glioma: 10 WHO grade II glioma, 13 WHO grade III glioma and 21 glioblastoma (GBM). All patients underwent stereotactic biopsy or tumour resection after 18 F-FET PET imaging. As well as histological analysis of tissue samples, DNA was subjected to epigenetic analysis using the Illumina 850 K methylation array. TACs, standardized uptake values corrected for background uptake in healthy tissue (SUVmax/BG), time to peak (TTP) and kinetic modelling parameters were correlated with histological diagnoses and with epigenetic signatures. Multivariate analyses were performed to evaluate the diagnostic accuracy of 18 F-FET PET in relation to the tumour groups identified by histological and methylation-based analysis. Epigenetic profiling led to substantial tumour reclassification, with six grade II/III gliomas reclassified as GBM. Overlap of HGG-typical TACs and LGG-typical TACs was dramatically reduced when tumours were clustered on the basis of their methylation profile. SUVmax/BG values of GBM were higher than those of LGGs following both histological diagnosis and methylation-based diagnosis. The differences in TTP between GBMs and grade II/III gliomas were greater following methylation-based diagnosis than following histological diagnosis. Kinetic modeling showed that relative K1 and fractal dimension (FD) values significantly differed in histology- and methylation-based GBM and grade II/III glioma between those diagnosed histologically and those diagnosed by methylation analysis. Multivariate analysis revealed slightly greater diagnostic accuracy with methylation-based diagnosis. IDH-mutant gliomas and GBM subgroups tended to differ in their 18 F-FET PET kinetics. The status of dynamic 18 F-FET PET as a biologically and clinically relevant imaging modality is confirmed in the context of molecular glioma diagnosis.

Probing conformational dynamics by photoinduced electron transfer

NASA Astrophysics Data System (ADS)

Neuweiler, Hannes; Herten, Dirk P.; Marme, N.; Knemeyer, J. P.; Piestert, Oliver; Tinnefeld, Philip; Sauer, Marcus

2004-07-01

We demonstrate how photoinduced electron transfer (PET) reactions can be successfully applied to monitor conformational dynamics in individual biopolymers. Single-pair fluorescence resonance energy transfer (FRET) experiments are ideally suited to study conformational dynamics occurring on the nanometer scale, e.g. during protein folding or unfolding. In contrast, conformational dynamics with functional significance, for example occurring in enzymes at work, often appear on much smaller spatial scales of up to several Angströms. Our results demonstrate that selective PET-reactions between fluorophores and amino acids or DNA nucleotides represent a versatile tool to measure small-scale conformational dynamics in biopolymers on a wide range of time scales, extending from nanoseconds to seconds, at the single-molecule level under equilibrium conditions. That is, the monitoring of conformational dynamics of biopolymers with temporal resolutions comparable to those within reach using new techniques of molecular dynamic simulations. We present data about structural changes of single biomolecules like DNA hairpins and peptides by using quenching electron transfer reactions between guanosine or tryptophan residues in close proximity to fluorescent dyes. Furthermore, we demonstrate that the strong distance dependence of charge separation reactions on the sub-nanometer scale can be used to develop conformationally flexible PET-biosensors. These sensors enable the detection of specific target molecules in the sub-picomolar range and allow one to follow their molecular binding dynamics with temporal resolution.

Shortened acquisition protocols for the quantitative assessment of the 2-tissue-compartment model using dynamic PET/CT 18F-FDG studies.

PubMed

Strauss, Ludwig G; Pan, Leyun; Cheng, Caixia; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2011-03-01

(18)F-FDG kinetics are quantified by a 2-tissue-compartment model. The routine use of dynamic PET is limited because of this modality's 1-h acquisition time. We evaluated shortened acquisition protocols up to 0-30 min regarding the accuracy for data analysis with the 2-tissue-compartment model. Full dynamic series for 0-60 min were analyzed using a 2-tissue-compartment model. The time-activity curves and the resulting parameters for the model were stored in a database. Shortened acquisition data were generated from the database using the following time intervals: 0-10, 0-16, 0-20, 0-25, and 0-30 min. Furthermore, the impact of adding a 60-min uptake value to the dynamic series was evaluated. The datasets were analyzed using dedicated software to predict the results of the full dynamic series. The software is based on a modified support vector machines (SVM) algorithm and predicts the compartment parameters of the full dynamic series. The SVM-based software provides user-independent results and was accurate at predicting the compartment parameters of the full dynamic series. If a squared correlation coefficient of 0.8 (corresponding to 80% explained variance of the data) was used as a limit, a shortened acquisition of 0-16 min was accurate at predicting the 60-min 2-tissue-compartment parameters. If a limit of 0.9 (90% explained variance) was used, a dynamic series of at least 0-20 min together with the 60-min uptake values is required. Shortened acquisition protocols can be used to predict the parameters of the 2-tissue-compartment model. Either a dynamic PET series of 0-16 min or a combination of a dynamic PET/CT series of 0-20 min and a 60-min uptake value is accurate for analysis with a 2-tissue-compartment model.

Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging.

PubMed

Williams, Jason M; Arlinghaus, Lori R; Rani, Sudheer D; Shone, Martha D; Abramson, Vandana G; Pendyala, Praveen; Chakravarthy, A Bapsi; Gorge, William J; Knowland, Joshua G; Lattanze, Ronald K; Perrin, Steven R; Scarantino, Charles W; Townsend, David W; Abramson, Richard G; Yankeelov, Thomas E

2016-12-01

To dynamically detect and characterize 18 F-fluorodeoxyglucose (FDG) dose infiltrations and evaluate their effects on positron emission tomography (PET) standardized uptake values (SUV) at the injection site and in control tissue. Investigational gamma scintillation sensors were topically applied to patients with locally advanced breast cancer scheduled to undergo limited whole-body FDG-PET as part of an ongoing clinical study. Relative to the affected breast, sensors were placed on the contralateral injection arm and ipsilateral control arm during the resting uptake phase prior to each patient's PET scan. Time-activity curves (TACs) from the sensors were integrated at varying intervals (0-10, 0-20, 0-30, 0-40, and 30-40 min) post-FDG and the resulting areas under the curve (AUCs) were compared to SUVs obtained from PET. In cases of infiltration, observed in three sensor recordings (30 %), the injection arm TAC shape varied depending on the extent and severity of infiltration. In two of these cases, TAC characteristics suggested the infiltration was partially resolving prior to image acquisition, although it was still apparent on subsequent PET. Areas under the TAC 0-10 and 0-20 min post-FDG were significantly different in infiltrated versus non-infiltrated cases (Mann-Whitney, p < 0.05). When normalized to control, all TAC integration intervals from the injection arm were significantly correlated with SUV peak and SUV max measured over the infiltration site (Spearman ρ ≥ 0.77, p < 0.05). Receiver operating characteristic (ROC) analyses, testing the ability of the first 10 min of post-FDG sensor data to predict infiltration visibility on the ensuing PET, yielded an area under the ROC curve of 0.92. Topical sensors applied near the injection site provide dynamic information from the time of FDG administration through the uptake period and may be useful in detecting infiltrations regardless of PET image field of view. This dynamic information may also complement the static PET image to better characterize the true extent of infiltrations.

Quantifying hypoxia in human cancers using static PET imaging.

PubMed

Taylor, Edward; Yeung, Ivan; Keller, Harald; Wouters, Bradley G; Milosevic, Michael; Hedley, David W; Jaffray, David A

2016-11-21

Compared to FDG, the signal of 18 F-labelled hypoxia-sensitive tracers in tumours is low. This means that in addition to the presence of hypoxic cells, transport properties contribute significantly to the uptake signal in static PET images. This sensitivity to transport must be minimized in order for static PET to provide a reliable standard for hypoxia quantification. A dynamic compartmental model based on a reaction-diffusion formalism was developed to interpret tracer pharmacokinetics and applied to static images of FAZA in twenty patients with pancreatic cancer. We use our model to identify tumour properties-well-perfused without substantial necrosis or partitioning-for which static PET images can reliably quantify hypoxia. Normalizing the measured activity in a tumour voxel by the value in blood leads to a reduction in the sensitivity to variations in 'inter-corporal' transport properties-blood volume and clearance rate-as well as imaging study protocols. Normalization thus enhances the correlation between static PET images and the FAZA binding rate K 3 , a quantity which quantifies hypoxia in a biologically significant way. The ratio of FAZA uptake in spinal muscle and blood can vary substantially across patients due to long muscle equilibration times. Normalized static PET images of hypoxia-sensitive tracers can reliably quantify hypoxia for homogeneously well-perfused tumours with minimal tissue partitioning. The ideal normalizing reference tissue is blood, either drawn from the patient before PET scanning or imaged using PET. If blood is not available, uniform, homogeneously well-perfused muscle can be used. For tumours that are not homogeneously well-perfused or for which partitioning is significant, only an analysis of dynamic PET scans can reliably quantify hypoxia.

Quantifying hypoxia in human cancers using static PET imaging

NASA Astrophysics Data System (ADS)

Taylor, Edward; Yeung, Ivan; Keller, Harald; Wouters, Bradley G.; Milosevic, Michael; Hedley, David W.; Jaffray, David A.

2016-11-01

Compared to FDG, the signal of 18F-labelled hypoxia-sensitive tracers in tumours is low. This means that in addition to the presence of hypoxic cells, transport properties contribute significantly to the uptake signal in static PET images. This sensitivity to transport must be minimized in order for static PET to provide a reliable standard for hypoxia quantification. A dynamic compartmental model based on a reaction-diffusion formalism was developed to interpret tracer pharmacokinetics and applied to static images of FAZA in twenty patients with pancreatic cancer. We use our model to identify tumour properties—well-perfused without substantial necrosis or partitioning—for which static PET images can reliably quantify hypoxia. Normalizing the measured activity in a tumour voxel by the value in blood leads to a reduction in the sensitivity to variations in ‘inter-corporal’ transport properties—blood volume and clearance rate—as well as imaging study protocols. Normalization thus enhances the correlation between static PET images and the FAZA binding rate K 3, a quantity which quantifies hypoxia in a biologically significant way. The ratio of FAZA uptake in spinal muscle and blood can vary substantially across patients due to long muscle equilibration times. Normalized static PET images of hypoxia-sensitive tracers can reliably quantify hypoxia for homogeneously well-perfused tumours with minimal tissue partitioning. The ideal normalizing reference tissue is blood, either drawn from the patient before PET scanning or imaged using PET. If blood is not available, uniform, homogeneously well-perfused muscle can be used. For tumours that are not homogeneously well-perfused or for which partitioning is significant, only an analysis of dynamic PET scans can reliably quantify hypoxia.

Spatio-temporal diffusion of dynamic PET images

NASA Astrophysics Data System (ADS)

Tauber, C.; Stute, S.; Chau, M.; Spiteri, P.; Chalon, S.; Guilloteau, D.; Buvat, I.

2011-10-01

Positron emission tomography (PET) images are corrupted by noise. This is especially true in dynamic PET imaging where short frames are required to capture the peak of activity concentration after the radiotracer injection. High noise results in a possible bias in quantification, as the compartmental models used to estimate the kinetic parameters are sensitive to noise. This paper describes a new post-reconstruction filter to increase the signal-to-noise ratio in dynamic PET imaging. It consists in a spatio-temporal robust diffusion of the 4D image based on the time activity curve (TAC) in each voxel. It reduces the noise in homogeneous areas while preserving the distinct kinetics in regions of interest corresponding to different underlying physiological processes. Neither anatomical priors nor the kinetic model are required. We propose an automatic selection of the scale parameter involved in the diffusion process based on a robust statistical analysis of the distances between TACs. The method is evaluated using Monte Carlo simulations of brain activity distributions. We demonstrate the usefulness of the method and its superior performance over two other post-reconstruction spatial and temporal filters. Our simulations suggest that the proposed method can be used to significantly increase the signal-to-noise ratio in dynamic PET imaging.

Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

PubMed

Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

2014-02-01

Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P < 0.001). Absence of (18)F-FET uptake in newly diagnosed astrocytic low-grade glioma does not generally indicate an indolent disease course. Among the (18)F-FET-positive gliomas, decreasing time-activity curves in dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

Textural features and SUV-based variables assessed by dual time point 18F-FDG PET/CT in locally advanced breast cancer.

PubMed

Garcia-Vicente, Ana María; Molina, David; Pérez-Beteta, Julián; Amo-Salas, Mariano; Martínez-González, Alicia; Bueno, Gloria; Tello-Galán, María Jesús; Soriano-Castrejón, Ángel

2017-12-01

To study the influence of dual time point 18F-FDG PET/CT in textural features and SUV-based variables and their relation among them. Fifty-six patients with locally advanced breast cancer (LABC) were prospectively included. All of them underwent a standard 18F-FDG PET/CT (PET-1) and a delayed acquisition (PET-2). After segmentation, SUV variables (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained. Eighteen three-dimensional (3D) textural measures were computed including: run-length matrices (RLM) features, co-occurrence matrices (CM) features, and energies. Differences between all PET-derived variables obtained in PET-1 and PET-2 were studied. Significant differences were found between the SUV-based parameters and MTV obtained in the dual time point PET/CT, with higher values of SUV-based variables and lower MTV in the PET-2 with respect to the PET-1. In relation with the textural parameters obtained in dual time point acquisition, significant differences were found for the short run emphasis, low gray-level run emphasis, short run high gray-level emphasis, run percentage, long run emphasis, gray-level non-uniformity, homogeneity, and dissimilarity. Textural variables showed relations with MTV and TLG. Significant differences of textural features were found in dual time point 18F-FDG PET/CT. Thus, a dynamic behavior of metabolic characteristics should be expected, with higher heterogeneity in delayed PET acquisition compared with the standard PET. A greater heterogeneity was found in bigger tumors.

Probing Allosteric Inhibition Mechanisms of the Hsp70 Chaperone Proteins Using Molecular Dynamics Simulations and Analysis of the Residue Interaction Networks.

PubMed

Stetz, Gabrielle; Verkhivker, Gennady M

2016-08-22

Although molecular mechanisms of allosteric regulation in the Hsp70 chaperones have been extensively studied at both structural and functional levels, the current understanding of allosteric inhibition of chaperone activities by small molecules is still lacking. In the current study, using a battery of computational approaches, we probed allosteric inhibition mechanisms of E. coli Hsp70 (DnaK) and human Hsp70 proteins by small molecule inhibitors PET-16 and novolactone. Molecular dynamics simulations and binding free energy analysis were combined with network-based modeling of residue interactions and allosteric communications to systematically characterize and compare molecular signatures of the apo form, substrate-bound, and inhibitor-bound chaperone complexes. The results suggested a mechanism by which the allosteric inhibitors may leverage binding energy hotspots in the interaction networks to stabilize a specific conformational state and impair the interdomain allosteric control. Using the network-based centrality analysis and community detection, we demonstrated that substrate binding may strengthen the connectivity of local interaction communities, leading to a dense interaction network that can promote an efficient allosteric communication. In contrast, binding of PET-16 to DnaK may induce significant dynamic changes and lead to a fractured interaction network and impaired allosteric communications in the DnaK complex. By using a mechanistic-based analysis of distance fluctuation maps and allosteric propensities of protein residues, we determined that the allosteric network in the PET-16 complex may be small and localized due to the reduced communication and low cooperativity of the substrate binding loops, which may promote the higher rates of substrate dissociation and the decreased substrate affinity. In comparison with the significant effect of PET-16, binding of novolactone to HSPA1A may cause only moderate network changes and preserve allosteric coupling between the allosteric pocket and the substrate binding region. The impact of novolactone on the conformational dynamics and allosteric communications in the HSPA1A complex was comparable to the substrate effect, which is consistent with the experimental evidence that PET-16, but not novolactone binding, can significantly decrease substrate affinity. We argue that the unique dynamic and network signatures of PET-16 and novolactone may be linked with the experimentally observed functional effects of these inhibitors on allosteric regulation and substrate binding.

Novel system using microliter order sample volume for measuring arterial radioactivity concentrations in whole blood and plasma for mouse PET dynamic study.

PubMed

Kimura, Yuichi; Seki, Chie; Hashizume, Nobuya; Yamada, Takashi; Wakizaka, Hidekatsu; Nishimoto, Takahiro; Hatano, Kentaro; Kitamura, Keishi; Toyama, Hiroshi; Kanno, Iwao

2013-11-21

This study aimed to develop a new system, named CD-Well, for mouse PET dynamic study. CD-Well allows the determination of time-activity curves (TACs) for arterial whole blood and plasma using 2-3 µL of blood per sample; the minute sample size is ideal for studies in small animals. The system has the following merits: (1) measures volume and radioactivity of whole blood and plasma separately; (2) allows measurements at 10 s intervals to capture initial rapid changes in the TAC; and (3) is compact and easy to handle, minimizes blood loss from sampling, and delay and dispersion of the TAC. CD-Well has 36 U-shaped channels. A drop of blood is sampled into the opening of the channel and stored there. After serial sampling is completed, CD-Well is centrifuged and scanned using a flatbed scanner to define the regions of plasma and blood cells. The length measured is converted to volume because the channels have a precise and uniform cross section. Then, CD-Well is exposed to an imaging plate to measure radioactivity. Finally, radioactivity concentrations are computed. We evaluated the performance of CD-Well in in vitro measurement and in vivo (18)F-fluorodeoxyglucose and [(11)C]2-carbomethoxy-3β-(4-fluorophenyl) tropane studies. In in vitro evaluation, per cent differences (mean±SE) from manual measurement were 4.4±3.6% for whole blood and 4.0±3.5% for plasma across the typical range of radioactivity measured in mouse dynamic study. In in vivo studies, reasonable TACs were obtained. The peaks were captured well, and the time courses coincided well with the TAC derived from PET imaging of the heart chamber. The total blood loss was less than 200 µL, which had no physiological effect on the mice. CD-Well demonstrates satisfactory performance, and is useful for mouse PET dynamic study.

Event-by-Event Continuous Respiratory Motion Correction for Dynamic PET Imaging.

PubMed

Yu, Yunhan; Chan, Chung; Ma, Tianyu; Liu, Yaqiang; Gallezot, Jean-Dominique; Naganawa, Mika; Kelada, Olivia J; Germino, Mary; Sinusas, Albert J; Carson, Richard E; Liu, Chi

2016-07-01

Existing respiratory motion-correction methods are applied only to static PET imaging. We have previously developed an event-by-event respiratory motion-correction method with correlations between internal organ motion and external respiratory signals (INTEX). This method is uniquely appropriate for dynamic imaging because it corrects motion for each time point. In this study, we applied INTEX to human dynamic PET studies with various tracers and investigated the impact on kinetic parameter estimation. The use of 3 tracers-a myocardial perfusion tracer, (82)Rb (n = 7); a pancreatic β-cell tracer, (18)F-FP(+)DTBZ (n = 4); and a tumor hypoxia tracer, (18)F-fluoromisonidazole ((18)F-FMISO) (n = 1)-was investigated in a study of 12 human subjects. Both rest and stress studies were performed for (82)Rb. The Anzai belt system was used to record respiratory motion. Three-dimensional internal organ motion in high temporal resolution was calculated by INTEX to guide event-by-event respiratory motion correction of target organs in each dynamic frame. Time-activity curves of regions of interest drawn based on end-expiration PET images were obtained. For (82)Rb studies, K1 was obtained with a 1-tissue model using a left-ventricle input function. Rest-stress myocardial blood flow (MBF) and coronary flow reserve (CFR) were determined. For (18)F-FP(+)DTBZ studies, the total volume of distribution was estimated with arterial input functions using the multilinear analysis 1 method. For the (18)F-FMISO study, the net uptake rate Ki was obtained with a 2-tissue irreversible model using a left-ventricle input function. All parameters were compared with the values derived without motion correction. With INTEX, K1 and MBF increased by 10% ± 12% and 15% ± 19%, respectively, for (82)Rb stress studies. CFR increased by 19% ± 21%. For studies with motion amplitudes greater than 8 mm (n = 3), K1, MBF, and CFR increased by 20% ± 12%, 30% ± 20%, and 34% ± 23%, respectively. For (82)Rb rest studies, INTEX had minimal effect on parameter estimation. The total volume of distribution of (18)F-FP(+)DTBZ and Ki of (18)F-FMISO increased by 17% ± 6% and 20%, respectively. Respiratory motion can have a substantial impact on dynamic PET in the thorax and abdomen. The INTEX method using continuous external motion data substantially changed parameters in kinetic modeling. More accurate estimation is expected with INTEX. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Dynamic FDG-PET Imaging to Differentiate Malignancies from Inflammation in Subcutaneous and In Situ Mouse Model for Non-Small Cell Lung Carcinoma (NSCLC).

PubMed

Yang, Zhen; Zan, Yunlong; Zheng, Xiujuan; Hai, Wangxi; Chen, Kewei; Huang, Qiu; Xu, Yuhong; Peng, Jinliang

2015-01-01

[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been widely used in oncologic procedures such as tumor diagnosis and staging. However, false-positive rates have been high, unacceptable and mainly caused by inflammatory lesions. Misinterpretations take place especially when non-subcutaneous inflammations appear at the tumor site, for instance in the lung. The aim of the current study is to evaluate the use of dynamic PET imaging procedure to differentiate in situ and subcutaneous non-small cell lung carcinoma (NSCLC) from inflammation, and estimate the kinetics of inflammations in various locations. Dynamic FDG-PET was performed on 33 female mice inoculated with tumor and/or inflammation subcutaneously or inside the lung. Standardized Uptake Values (SUVs) from static imaging (SUVmax) as well as values of influx rate constant (Ki) of compartmental modeling from dynamic imaging were obtained. Static and kinetic data from different lesions (tumor and inflammations) or different locations (subcutaneous, in situ and spontaneous group) were compared. Values of SUVmax showed significant difference in subcutaneous tumor and inflammation (p<0.01), and in inflammations from different locations (p<0.005). However, SUVmax showed no statistical difference between in situ tumor and inflammation (p = 1.0) and among tumors from different locations (subcutaneous and in situ, p = 0.91). Values of Ki calculated from compartmental modeling showed significant difference between tumor and inflammation both subcutaneously (p<0.005) and orthotopically (p<0.01). Ki showed also location specific values for inflammations (subcutaneous, in situ and spontaneous, p<0.015). However, Ki of tumors from different locations (subcutaneous and in situ) showed no significant difference (p = 0.46). In contrast to static PET based SUVmax, both subcutaneous and in situ inflammations and malignancies can be differentiated via dynamic FDG-PET based Ki. Moreover, Values of influx rate constant Ki from compartmental modeling can offer an assessment for inflammations at different locations of the body, which also implies further validation is necessary before the replacement of in situ inflammation with its subcutaneous counterpart in animal experiments.

Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

PubMed

Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in total 43 (18)F-FDG avid metastases; these patients were excluded from radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. (18)F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers' kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy.

Combined use of 18F-FDG and 18F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study

PubMed Central

Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose (18F-FDG) and of fluorine-18-fluoromisonidazole (18F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with 18F-FDG and 18F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. 18F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased 18F-FDG uptake. Six patients demonstrated also in total 43 18F-FDG avid metastases; these patients were excluded from radiotherapy. 18F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly 18F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for 18F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for 18F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. 18F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. 18F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the 18F-FDG avid NSCLCs. Lack of correlation between the two tracers’ kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy. PMID:25973334

Diagnostic value of quantitative assessment of cardiac 18F-fluoro-2-deoxyglucose uptake in suspected cardiac sarcoidosis.

PubMed

Lebasnier, Adrien; Legallois, Damien; Bienvenu, Boris; Bergot, Emmanuel; Desmonts, Cédric; Zalcman, Gérard; Agostini, Denis; Manrique, Alain

2018-06-01

The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis. Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic 18 F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min -1 )/global Ki (min -1 ) was determined using a validated software (Carimas ® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic 18 F-FDG PET/CT analysis to diagnose cardiac sarcoidosis. Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513 ± 0.175 vs. 0.205 ± 0.081; p = 0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%. Our results suggest that quantitative analysis of cardiac dynamic 18 F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.

An open tool for input function estimation and quantification of dynamic PET FDG brain scans.

PubMed

Bertrán, Martín; Martínez, Natalia; Carbajal, Guillermo; Fernández, Alicia; Gómez, Álvaro

2016-08-01

Positron emission tomography (PET) analysis of clinical studies is mostly restricted to qualitative evaluation. Quantitative analysis of PET studies is highly desirable to be able to compute an objective measurement of the process of interest in order to evaluate treatment response and/or compare patient data. But implementation of quantitative analysis generally requires the determination of the input function: the arterial blood or plasma activity which indicates how much tracer is available for uptake in the brain. The purpose of our work was to share with the community an open software tool that can assist in the estimation of this input function, and the derivation of a quantitative map from the dynamic PET study. Arterial blood sampling during the PET study is the gold standard method to get the input function, but is uncomfortable and risky for the patient so it is rarely used in routine studies. To overcome the lack of a direct input function, different alternatives have been devised and are available in the literature. These alternatives derive the input function from the PET image itself (image-derived input function) or from data gathered from previous similar studies (population-based input function). In this article, we present ongoing work that includes the development of a software tool that integrates several methods with novel strategies for the segmentation of blood pools and parameter estimation. The tool is available as an extension to the 3D Slicer software. Tests on phantoms were conducted in order to validate the implemented methods. We evaluated the segmentation algorithms over a range of acquisition conditions and vasculature size. Input function estimation algorithms were evaluated against ground truth of the phantoms, as well as on their impact over the final quantification map. End-to-end use of the tool yields quantification maps with [Formula: see text] relative error in the estimated influx versus ground truth on phantoms. The main contribution of this article is the development of an open-source, free to use tool that encapsulates several well-known methods for the estimation of the input function and the quantification of dynamic PET FDG studies. Some alternative strategies are also proposed and implemented in the tool for the segmentation of blood pools and parameter estimation. The tool was tested on phantoms with encouraging results that suggest that even bloodless estimators could provide a viable alternative to blood sampling for quantification using graphical analysis. The open tool is a promising opportunity for collaboration among investigators and further validation on real studies.

Imaging Alzheimer's disease pathophysiology with PET

PubMed Central

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Benedet, Andréa L.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa-Neto, Pedro

2016-01-01

ABSTRACT Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD. PMID:29213438

Joint estimation of subject motion and tracer kinetic parameters of dynamic PET data in an EM framework

NASA Astrophysics Data System (ADS)

Jiao, Jieqing; Salinas, Cristian A.; Searle, Graham E.; Gunn, Roger N.; Schnabel, Julia A.

2012-02-01

Dynamic Positron Emission Tomography is a powerful tool for quantitative imaging of in vivo biological processes. The long scan durations necessitate motion correction, to maintain the validity of the dynamic measurements, which can be particularly challenging due to the low signal-to-noise ratio (SNR) and spatial resolution, as well as the complex tracer behaviour in the dynamic PET data. In this paper we develop a novel automated expectation-maximisation image registration framework that incorporates temporal tracer kinetic information to correct for inter-frame subject motion during dynamic PET scans. We employ the Zubal human brain phantom to simulate dynamic PET data using SORTEO (a Monte Carlo-based simulator), in order to validate the proposed method for its ability to recover imposed rigid motion. We have conducted a range of simulations using different noise levels, and corrupted the data with a range of rigid motion artefacts. The performance of our motion correction method is compared with pairwise registration using normalised mutual information as a voxel similarity measure (an approach conventionally used to correct for dynamic PET inter-frame motion based solely on intensity information). To quantify registration accuracy, we calculate the target registration error across the images. The results show that our new dynamic image registration method based on tracer kinetics yields better realignment of the simulated datasets, halving the target registration error when compared to the conventional method at small motion levels, as well as yielding smaller residuals in translation and rotation parameters. We also show that our new method is less affected by the low signal in the first few frames, which the conventional method based on normalised mutual information fails to realign.

18F-FDG PET imaging for identifying the dynamics of intestinal disease caused by SFTSV infection in a mouse model.

PubMed

Hayasaka, Daisuke; Nishi, Kodai; Fuchigami, Takeshi; Shiogama, Kazuya; Onouchi, Takanori; Shimada, Satoshi; Tsutsumi, Yutaka; Morita, Kouichi

2016-01-05

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that causes fever, enteritis, thrombocytopenia, and leucopenia and can be fatal in up to 30% of cases. However, the mechanism of severe disease is not fully understood. Molecular imaging approaches, such as positron-emission tomography (PET), are functional in vivo imaging techniques that provide real-time dynamics of disease progression, assessments of pharmacokinetics, and diagnoses for disease progression. Molecular imaging also potentially provides useful approaches to explore the pathogenesis of viral infections. Thus, the purpose of this study was to image the pathological features of SFTSV infection in vivo by PET imaging. In a mouse model, we showed that 18F-FDG accumulations clearly identified the intestinal tract site as a pathological site. We also demonstrated that 18F-FDG PET imaging can assess disease progression and response to antiserum therapy within the same individual. This is the first report demonstrating a molecular imaging strategy for SFTSV infection. Our results provide potentially useful information for preclinical studies such as the elucidation of the mechanism of SFTSV infection in vivo and the assessment of drugs for SFTS treatment.

Dynamic Functional Imaging of Brain Glucose Utilization using fPET-FDG

PubMed Central

Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

2014-01-01

Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism. PMID:24936683

In vivo quantitative imaging of photoassimilate transport dynamics and allocation in large plants using a commercial positron emission tomography (PET) scanner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karve, Abhijit A.; Alexoff, David; Kim, Dohyun

Although important aspects of whole-plant carbon allocation in crop plants (e.g., to grain) occur late in development when the plants are large, techniques to study carbon transport and allocation processes have not been adapted for large plants. Positron emission tomography (PET), developed for dynamic imaging in medicine, has been applied in plant studies to measure the transport and allocation patterns of carbohydrates, nutrients, and phytohormones labeled with positron-emitting radioisotopes. However, the cost of PET and its limitation to smaller plants has restricted its use in plant biology. Here we describe the adaptation and optimization of a commercial clinical PET scannermore » to measure transport dynamics and allocation patterns of 11C-photoassimilates in large crops. Based on measurements of a phantom, we optimized instrument settings, including use of 3-D mode and attenuation correction to maximize the accuracy of measurements. To demonstrate the utility of PET, we measured 11C-photoassimilate transport and allocation in Sorghum bicolor, an important staple crop, at vegetative and reproductive stages (40 and 70 days after planting; DAP). The 11C-photoassimilate transport speed did not change over the two developmental stages. However, within a stem, transport speeds were reduced across nodes, likely due to higher 11C-photoassimilate unloading in the nodes. Photosynthesis in leaves and the amount of 11C that was exported to the rest of the plant decreased as plants matured. In young plants, exported 11C was allocated mostly (88 %) to the roots and stem, but in flowering plants (70 DAP) the majority of the exported 11C (64 %) was allocated to the apex. Our results show that commercial PET scanners can be used reliably to measure whole-plant C-allocation in large plants nondestructively including, importantly, allocation to roots in soil. This capability revealed extreme changes in carbon allocation in sorghum plants, as they advanced to maturity. Further, our results suggest that nodes may be important control points for photoassimilate distribution in crops of the family Poaceae. In conclusion, quantifying real-time carbon allocation and photoassimilate transport dynamics, as demonstrated here, will be important for functional genomic studies to unravel the mechanisms controlling phloem transport in large crop plants, which will provide crucial insights for improving yields.« less

In vivo quantitative imaging of photoassimilate transport dynamics and allocation in large plants using a commercial positron emission tomography (PET) scanner

DOE PAGES

Karve, Abhijit A.; Alexoff, David; Kim, Dohyun; ...

2015-11-09

Although important aspects of whole-plant carbon allocation in crop plants (e.g., to grain) occur late in development when the plants are large, techniques to study carbon transport and allocation processes have not been adapted for large plants. Positron emission tomography (PET), developed for dynamic imaging in medicine, has been applied in plant studies to measure the transport and allocation patterns of carbohydrates, nutrients, and phytohormones labeled with positron-emitting radioisotopes. However, the cost of PET and its limitation to smaller plants has restricted its use in plant biology. Here we describe the adaptation and optimization of a commercial clinical PET scannermore » to measure transport dynamics and allocation patterns of 11C-photoassimilates in large crops. Based on measurements of a phantom, we optimized instrument settings, including use of 3-D mode and attenuation correction to maximize the accuracy of measurements. To demonstrate the utility of PET, we measured 11C-photoassimilate transport and allocation in Sorghum bicolor, an important staple crop, at vegetative and reproductive stages (40 and 70 days after planting; DAP). The 11C-photoassimilate transport speed did not change over the two developmental stages. However, within a stem, transport speeds were reduced across nodes, likely due to higher 11C-photoassimilate unloading in the nodes. Photosynthesis in leaves and the amount of 11C that was exported to the rest of the plant decreased as plants matured. In young plants, exported 11C was allocated mostly (88 %) to the roots and stem, but in flowering plants (70 DAP) the majority of the exported 11C (64 %) was allocated to the apex. Our results show that commercial PET scanners can be used reliably to measure whole-plant C-allocation in large plants nondestructively including, importantly, allocation to roots in soil. This capability revealed extreme changes in carbon allocation in sorghum plants, as they advanced to maturity. Further, our results suggest that nodes may be important control points for photoassimilate distribution in crops of the family Poaceae. In conclusion, quantifying real-time carbon allocation and photoassimilate transport dynamics, as demonstrated here, will be important for functional genomic studies to unravel the mechanisms controlling phloem transport in large crop plants, which will provide crucial insights for improving yields.« less

Correcting (18)F-fluoride PET static scan measurements of skeletal plasma clearance for tracer efflux from bone.

PubMed

Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac; Blake, Glen M

2014-03-01

The aim of the study was to examine whether (18)F-fluoride PET ((18)F-PET) static scan measurements of bone plasma clearance (Ki) can be corrected for tracer efflux from bone from the time of injection. The efflux of tracer from bone mineral to plasma was described by a first-order rate constant kloss. A modified Patlak analysis was applied to 60-min dynamic (18)F-PET scans of the spine and hip acquired during trials on the bone anabolic agent teriparatide to find the best-fit values of kloss at the lumbar spine, total hip and femoral shaft. The resulting values of kloss were used to extrapolate the modified Patlak plots to 120 min after injection and derive a sequence of static scan estimates of Ki at 4-min intervals that were compared with the Patlak Ki values from the 60-min dynamic scans. A comparison was made with the results of the standard static scan analysis, which assumes kloss=0. The best-fit values of kloss for the spine and hip regions of interest averaged 0.006/min and did not change when patients were treated with teriparatide. Static scan values of Ki calculated using the modified analysis with kloss=0.006/min were independent of time between 10 and 120 min after injection and were in close agreement with findings from the dynamic scans. In contrast, by 2 h after injection the static scan Ki values calculated using the standard analysis underestimated the dynamic scan results by 20%. Using a modified analysis that corrects for F efflux from bone, estimates of Ki from static PET scans can be corrected for time up to 2 h after injection. This simplified approach may obviate the need to perform dynamic scans and hence shorten the scanning procedure for the patient and reduce the cost of studies. It also enables reliable estimates of Ki to be obtained from multiple skeletal sites with a single injection of tracer.

Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status.

PubMed

Verger, Antoine; Stoffels, Gabriele; Bauer, Elena K; Lohmann, Philipp; Blau, Tobias; Fink, Gereon R; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

2018-03-01

The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18 F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBR mean/max ), as well as dynamic parameters (time-to-peak and slope) of 18 F-FET uptake were calculated. Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBR mean , TBR max , TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P < 0.01). TBR mean showed the best diagnostic performance (cut-off 1.95; sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBR mean , TBR max , TTP, and slope discriminated between gliomas with and without IDH mutation (p < 0.01). The best diagnostic performance was obtained for the combination of TTP with TBR max or slope (accuracy, 73%). Data suggest that static and dynamic 18 F-FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18 F-FET PET.

Evaluation of dynamic row-action maximum likelihood algorithm reconstruction for quantitative 15O brain PET.

PubMed

Ibaraki, Masanobu; Sato, Kaoru; Mizuta, Tetsuro; Kitamura, Keishi; Miura, Shuichi; Sugawara, Shigeki; Shinohara, Yuki; Kinoshita, Toshibumi

2009-09-01

A modified version of row-action maximum likelihood algorithm (RAMLA) using a 'subset-dependent' relaxation parameter for noise suppression, or dynamic RAMLA (DRAMA), has been proposed. The aim of this study was to assess the capability of DRAMA reconstruction for quantitative (15)O brain positron emission tomography (PET). Seventeen healthy volunteers were studied using a 3D PET scanner. The PET study included 3 sequential PET scans for C(15)O, (15)O(2) and H (2) (15) O. First, the number of main iterations (N (it)) in DRAMA was optimized in relation to image convergence and statistical image noise. To estimate the statistical variance of reconstructed images on a pixel-by-pixel basis, a sinogram bootstrap method was applied using list-mode PET data. Once the optimal N (it) was determined, statistical image noise and quantitative parameters, i.e., cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)) and oxygen extraction fraction (OEF) were compared between DRAMA and conventional FBP. DRAMA images were post-filtered so that their spatial resolutions were matched with FBP images with a 6-mm FWHM Gaussian filter. Based on the count recovery data, N (it) = 3 was determined as an optimal parameter for (15)O PET data. The sinogram bootstrap analysis revealed that DRAMA reconstruction resulted in less statistical noise, especially in a low-activity region compared to FBP. Agreement of quantitative values between FBP and DRAMA was excellent. For DRAMA images, average gray matter values of CBF, CBV, CMRO(2) and OEF were 46.1 +/- 4.5 (mL/100 mL/min), 3.35 +/- 0.40 (mL/100 mL), 3.42 +/- 0.35 (mL/100 mL/min) and 42.1 +/- 3.8 (%), respectively. These values were comparable to corresponding values with FBP images: 46.6 +/- 4.6 (mL/100 mL/min), 3.34 +/- 0.39 (mL/100 mL), 3.48 +/- 0.34 (mL/100 mL/min) and 42.4 +/- 3.8 (%), respectively. DRAMA reconstruction is applicable to quantitative (15)O PET study and is superior to conventional FBP in terms of image quality.

18F Fluorocholine Dynamic Time-of-Flight PET/MR Imaging in Patients with Newly Diagnosed Intermediate- to High-Risk Prostate Cancer: Initial Clinical-Pathologic Comparisons.

PubMed

Choi, Joon Young; Yang, Jaewon; Noworolski, Susan M; Behr, Spencer; Chang, Albert J; Simko, Jeffry P; Nguyen, Hao G; Carroll, Peter R; Kurhanewicz, John; Seo, Youngho

2017-02-01

Purpose To investigate the initial clinical value of fluorine 18 ( 18 F) fluorocholine (FCH) dynamic positron emission tomography (PET)/magnetic resonance (MR) imaging by comparing its parameters with clinical-pathologic findings in patients with newly diagnosed intermediate- to high-risk prostate cancer (PCa) who plan to undergo radical prostatectomy. Materials and Methods The institutional review board approved the study protocol, and informed written consent was obtained from all subjects for this HIPAA-compliant study. Twelve men (mean age ± standard deviation, 61.7 years ± 8.4; range, 46-74 years) with untreated intermediate- to high-risk PCa characterized according to Cancer of the Prostate Risk Assessment (CAPRA) underwent preoperative FCH dynamic PET/MR imaging followed by radical prostatectomy between April and November 2015. PET/MR imaging parameters including average and maximum K1 (delivery rate constant) and standardized uptake values (SUVs) and Prostate Imaging Reporting and Data System (PI-RADS) version 2 scores were measured and compared with clinical-pathologic characteristics. For statistical analysis, the Spearman rank correlation and Mann-Whitney U tests were performed. Results Of the PET parameters, maximum SUV of primary tumors showed significant correlations with several clinical-pathologic parameters including serum prostate-specific antigen level (ρ = 0.71, P = .01), pathologic stage (ρ = 0.59, P = .043), and postsurgical CAPRA score (ρ = 0.72, P = .008). The overall PI-RADS score showed significant correlations with pathologic tumor volume (ρ = 0.81, P < .001), percentage of tumor cells with Gleason scores greater than 3 (ρ = 0.59, P = .02), and postsurgical CAPRA score (ρ = 0.58, P = .046). The high-risk postsurgical CAPRA score patient group had a significantly higher maximum SUV than did the intermediate-risk group. Combined PET and MR imaging showed improved sensitivity (88%) for prediction of pathologic extraprostatic extension compared with that with MR imaging (50%) and PET (75%) performed separately. Conclusion Maximum SUVs and PI-RADS scores from FCH PET/MR imaging show good correlation with clinical-pathologic characteristics, such as postsurgical CAPRA score, which are related to prognosis in patients with newly diagnosed intermediate- to high-risk PCa. © RSNA, 2016 Online supplemental material is available for this article.

Reconstruction of an input function from a dynamic PET water image using multiple tissue curves

NASA Astrophysics Data System (ADS)

Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro

2016-08-01

Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with {{\\text{H}}2} 15O or C15O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic {{\\text{H}}2} 15O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  <8% and the calculated CBF values showed a tight correlation (r  =  0.97). The simulation showed that errors associated with the assumed parameters were  <10%, and that the optimal number of tissue curves to be used was around 500. Our results demonstrate that IDIF can be reconstructed directly from tissue curves obtained through {{\\text{H}}2} 15O PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

18F-Fluorocholine PET/CT Complementing the Role of Dynamic Contrast-Enhanced MRI for Providing Comprehensive Diagnostic Workup in Prostate Cancer Patients With Suspected Relapse Following Radical Prostatectomy.

PubMed

Vadi, Shelvin Kumar; Singh, Baljinder; Basher, Rajender K; Watts, Ankit; Sood, Ashwani K; Lal, Anupam; Kakkar, Nandita; Singh, S K

2017-08-01

The aim of this study was to compare the diagnostic performance of F-fluorocholine (FCH) PET/CT and dynamic contrast-enhanced MRI (DCE-MRI) of pelvis in restaging prostate cancer (PC) patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Twenty PC patients who had undergone RP and had BCR were recruited in this study. All the patients underwent whole-body FCH PET/CT and DCE-MRI of the pelvis. An overall pattern of recurrent disease was analyzed, and diagnostic accuracy for the detection of pelvic disease recurrence by the 2 modalities was evaluated by taking histopathologic analysis as the criterion standard. The whole-body FCH PET/CT images were also analyzed separately for the presence of any extra lesion(s). The initial mean Gleason score was 6.3 ± 1.53 (range, 4-9). The mean prostate-specific antigen levels at the time of relapse were 1.9 ± 2.87 ng/mL (range, 0.24-13.2 ng/mL). MRI findings were positive for primary tumor recurrence in the prostate bed in 6 patients (6/20 [30.0%]), pelvic lymph node metastases in 4 patients (4/20 [20.0%]), and for pelvic skeletal metastases in 2 patients (2/20 [10.0%]), respectively. On the other hand, FCH PET/CT results were positive in the corresponding sites in 7 (7/20 [35.0%]), 9 (9/20 [45.0%]), and 2 patients (2/20 [10.0%]), respectively. F-fluorocholine PET/CT and MRI showed comparable results in terms of sensitivity, specificity, and positive and negative predictive values for PC characterization. The whole-body FCH PET/CT was found to be useful in identifying unknown distant metastases in a significant proportion of patients. The correlative whole-body FCH PET/CT and pelvic DCE-MRI offer a complementary and comprehensive diagnostic workup for better management of PC patients with BCR following RP.

Joint PET-MR respiratory motion models for clinical PET motion correction

NASA Astrophysics Data System (ADS)

Manber, Richard; Thielemans, Kris; Hutton, Brian F.; Wan, Simon; McClelland, Jamie; Barnes, Anna; Arridge, Simon; Ourselin, Sébastien; Atkinson, David

2016-09-01

Patient motion due to respiration can lead to artefacts and blurring in positron emission tomography (PET) images, in addition to quantification errors. The integration of PET with magnetic resonance (MR) imaging in PET-MR scanners provides complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. In this paper we build on previous work to form a methodology for respiratory motion correction of PET data, and show it can improve PET image quality whilst having minimal impact on clinical PET-MR protocols. We introduce a joint PET-MR motion model, using only 1 min per PET bed position of simultaneously acquired PET and MR data to provide a respiratory motion correspondence model that captures inter-cycle and intra-cycle breathing variations. In the model setup, 2D multi-slice MR provides the dynamic imaging component, and PET data, via low spatial resolution framing and principal component analysis, provides the model surrogate. We evaluate different motion models (1D and 2D linear, and 1D and 2D polynomial) by computing model-fit and model-prediction errors on dynamic MR images on a data set of 45 patients. Finally we apply the motion model methodology to 5 clinical PET-MR oncology patient datasets. Qualitative PET reconstruction improvements and artefact reduction are assessed with visual analysis, and quantitative improvements are calculated using standardised uptake value (SUVpeak and SUVmax) changes in avid lesions. We demonstrate the capability of a joint PET-MR motion model to predict respiratory motion by showing significantly improved image quality of PET data acquired before the motion model data. The method can be used to incorporate motion into the reconstruction of any length of PET acquisition, with only 1 min of extra scan time, and with no external hardware required.

18F-FET PET prior to recurrent high-grade glioma re-irradiation-additional prognostic value of dynamic time-to-peak analysis and early static summation images?

PubMed

Fleischmann, Daniel F; Unterrainer, Marcus; Bartenstein, Peter; Belka, Claus; Albert, Nathalie L; Niyazi, Maximilian

2017-04-01

Most high-grade gliomas (HGG) recur after initial multimodal therapy and re-irradiation (Re-RT) has been shown to be a valuable re-treatment option in selected patients. We evaluated the prognostic value of dynamic time-to-peak analysis and early static summation images in O-(2- 18 F-fluoroethyl)-l-tyrosine ( 18 F-FET) PET for patients treated with Re-RT ± concomitant bevacizumab. We retrospectively analyzed 72 patients suffering from recurrent HGG with 18 F-FET PET prior to Re-RT. PET analysis revealed the maximal tumor-to-background-ratio (TBR max ), the biological tumor volume, the number of PET-foci and pattern of time-activity-curves (TACs; increasing vs. decreasing). Furthermore, the novel PET parameters early TBR max (at 5-15 min post-injection) and minimal time-to-peak (TTP min ) were evaluated. Additional analysis was performed for gender, age, KPS, O6-methylguanine-DNA methyltransferase methylation status, isocitrate dehydrogenase 1 mutational status, WHO grade and concomitant bevacizumab therapy. The influence of PET and clinical parameters on post-recurrence survival (PRS) was investigated. Shorter TTP min was related to shorter PRS after Re-RT with 6 months for TTP min  < 12.5 min, 7 months for TTP min 12.5-25 min and 11 months for TTP min >25 min (p = 0.027). TTP min had a significant impact on PRS both on univariate (p = 0.027; continuous) and multivariate analysis (p = 0.011; continuous). Other factors significantly related to PRS on multivariate analysis were increasing vs. decreasing TACs (p = 0.008) and Karnofsky Performance Score (p = 0.015; <70 vs. ≥70). Early TBR max as well as the other conventional PET parameters were not significantly related to PRS on univariate analysis. Dynamic 18 F-FET PET with TTP min provides a high prognostic value for recurrent HGG prior to Re-RT, whereas early TBR max does not. Dynamic 18 F-FET PET using TTP min might help to personalize Re-RT treatment regimens in future through voxelwise TTP min analysis for dose painting purposes and PET-guided dose escalation.

Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma.

PubMed

Göttler, Jens; Lukas, Mathias; Kluge, Anne; Kaczmarz, Stephan; Gempt, Jens; Ringel, Florian; Mustafa, Mona; Meyer, Bernhard; Zimmer, Claus; Schwaiger, Markus; Förster, Stefan; Preibisch, Christine; Pyka, Thomas

2017-03-01

18 F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

Whole-body PET/CT evaluation of tumor perfusion using generator-based 62Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II): validation by direct comparison to 15O-water in metastatic renal cell carcinoma.

PubMed

Fletcher, James W; Logan, Theodore F; Eitel, Jacob A; Mathias, Carla J; Ng, Yen; Lacy, Jeffrey L; Hutchins, Gary D; Green, Mark A

2015-01-01

This study was undertaken to demonstrate the feasibility of whole-body (62)Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II) ((62)Cu-ETS) PET/CT tumor perfusion imaging in patients with metastatic renal carcinoma and to validate (62)Cu-ETS as a quantitative marker of tumor perfusion by direct comparison with (15)O-water perfusion imaging. PET/CT imaging of 10 subjects with stage IV renal cell cancer was performed after intravenous administration of (15)O-water (10-min dynamic list-mode study) with the heart and at least 1 tumor in the PET field of view, followed 10 min later by intravenous (62)Cu-ETS (6-min list-mode study). Whole-body (62)Cu imaging was then performed from 6 to 20 min at 2-3 min/bed position. Blood flow (K1) was quantified with both agents for normal and malignant tissues in the 21.7-cm dynamic field of view. The required arterial input functions were derived from the left atrium and, in the case of (62)Cu-ETS, corrected for partial decomposition of the agent by blood with data from an in vitro analysis using a sample of each patient's blood. This imaging protocol was repeated at an interval of 3-4 wk after initiation of a standard clinical treatment course of the antiangiogenic agent sunitinib. All subjects received the scheduled (62)Cu-ETS doses for the dynamic and subsequent whole-body PET/CT scans, but technical issues resulted in no baseline (15)O-water data for 2 subjects. Direct comparisons of the perfusion estimates for normal tissues and tumor metastases were made in 18 paired baseline and treatment studies (10 subjects; 8 baseline studies, 10 repeated studies during treatment). There was an excellent correlation between the blood flow estimates made with (62)Cu-ETS and (15)O-water for normal tissues (muscle, thyroid, myocardium) and malignant lesions (pulmonary nodules, bone lesions); the regression line was y = 0.85x + 0.15, R(2) = 0.83, for the 88 regions analyzed. (62)Cu-ETS provided high-quality whole-body PET/CT images, and (62)Cu-ETS measures of blood flow were highly and linearly correlated with (15)O-water-derived K1 values (mL(-1) ⋅ min(-1) ⋅ g). This tracer is suitable for use as a PET tracer of tumor perfusion in patients with metastatic renal cell carcinoma. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

PubMed

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans.

PubMed

Lohmann, Philipp; Stoffels, Gabriele; Ceccon, Garry; Rapp, Marion; Sabel, Michael; Filss, Christian P; Kamp, Marcel A; Stegmayr, Carina; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

2017-07-01

We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max . Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

Comparison of dynamic FDG-microPET study in a rabbit turpentine-induced inflammatory model and in a rabbit VX2 tumor model.

PubMed

Hamazawa, Yoshimasa; Koyama, Koichi; Okamura, Terue; Wada, Yasuhiro; Wakasa, Tomoko; Okuma, Tomohisa; Watanabe, Yasuyoshi; Inoue, Yuichi

2007-01-01

We investigated the optimum time for the differentiation tumor from inflammation using dynamic FDG-microPET scans obtained by a MicroPET P4 scanner in animal models. Forty-six rabbits with 92 inflammatory lesions that were induced 2, 5, 7, 14, 30 and 60 days after 0.2 ml (Group 1) or 1.0 ml (Group 2) of turpentine oil injection were used as inflammatory models. Five rabbits with 10 VX2 tumors were used as the tumor model. Helical CT scans were performed before the PET studies. In the PET study, after 4 hours fasting, and following transmission scans and dynamic emission data acquisitions were performed until 2 hours after intravenous FDG injection. Images were reconstructed every 10 minutes using a filtered-back projection method. PET images were analyzed visually referring to CT images. For quantitative analysis, the inflammation-to-muscle (I/M) ratio and tumor-to-muscle (T/M) ratio were calculated after regions of interest were set in tumors and muscles referring to CT images and the time-I/M ratio and time-T/M ratio curves (TRCs) were prepared to show the change over time in these ratios. The histological appearance of both inflammatory lesions and tumor lesions were examined and compared with the CT and FDG-microPET images. In visual and quantitative analysis, All the I/M ratios and the T/M ratios increased over time except that Day 60 of Group 1 showed an almost flat curve. The TRC of the T/M ratio showed a linear increasing curve over time, while that of the I/M ratios showed a parabolic increasing over time at the most. FDG uptake in the inflammatory lesions reflected the histological findings. For differentiating tumors from inflammatory lesions with the early image acquired at 40 min for dual-time imaging, the delayed image must be acquired 30 min after the early image, while imaging at 90 min or later after intravenous FDG injection was necessary in single-time-point imaging. Our results suggest the possibility of shortening the overall testing time in clinical practice by adopting dual-time-point imaging rather than single-time-point imaging.

The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma.

PubMed

Galldiks, Norbert; Stoffels, Gabriele; Filss, Christian; Rapp, Marion; Blau, Tobias; Tscherpel, Caroline; Ceccon, Garry; Dunkl, Veronika; Weinzierl, Martin; Stoffel, Michael; Sabel, Michael; Fink, Gereon R; Shah, Nadim J; Langen, Karl-Josef

2015-09-01

We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma. We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test. Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak <45 min was present (sensitivity, 93%; specificity, 100%; accuracy, 93%; positive predictive value, 100%; P < .001). Static and dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma.

PubMed

Nakajima, Reiko; Abe, Koichiro; Kondo, Tsunenori; Tanabe, Kazunari; Sakai, Shuji

2016-06-01

We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. • ED and WB FDG-PET/ CT helps to assess patients with RCC • ED FDG-PET/CT enabled differentiation between CCC and N-CCC • FDG accumulation in the WB phase reflects tumour aggressiveness • Management of RCC is improved by ED and WB FDG-PET/CT.

TH-E-202-02: The Use of Hypoxia PET Imaging for Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humm, J.

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

TH-E-202-00: PET for Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

TH-E-202-03: PET for Tumor Response Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, W.

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer.

PubMed

Mönnich, David; Thorwarth, Daniela; Leibfarth, Sara; Pfannenberg, Christina; Reischl, Gerald; Mauz, Paul-Stefan; Nikolaou, Konstantin; la Fougère, Christian; Zips, Daniel; Welz, Stefan

2017-11-01

PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [ 18 F]-fluorodeoxyglucose (FDG) and [ 18 F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTV prim ) were segmented: a highly FDG-avid volume V FDG , a hypoxic volume on the static FMISO image acquired four hours post tracer injection (V H ) and a retention/perfusion volume (V M ) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. Sizes of PET-based volumes and the GTV prim are significantly different (GTV prim >V FDG >V H >V M ; p < .05). V H is covered by V FDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of V M is less pronounced. With respect to V FDG and V H , the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

Simultaneous water activation and glucose metabolic rate imaging with PET

NASA Astrophysics Data System (ADS)

Verhaeghe, Jeroen; Reader, Andrew J.

2013-02-01

A novel imaging and signal separation strategy is proposed to be able to separate [18F]FDG and multiple [15O]H2O signals from a simultaneously acquired dynamic PET acquisition of the two tracers. The technique is based on the fact that the dynamics of the two tracers are very distinct. By adopting an appropriate bolus injection strategy and by defining tailored sets of basis functions that model either the FDG or water component, it is possible to separate the FDG and water signal. The basis functions are inspired from the spectral analysis description of dynamic PET studies and are defined as the convolution of estimated generating functions (GFs) with a set of decaying exponential functions. The GFs are estimated from the overall measured head curve, while the decaying exponential functions are pre-determined. In this work, the time activity curves (TACs) are modelled post-reconstruction but the model can be incorporated in a global 4D reconstruction strategy. Extensive PET simulation studies are performed considering single [18F]FDG and 6 [15O]H2O bolus injections for a total acquisition time of 75 min. The proposed method is evaluated at multiple noise levels and different parameters were estimated such as [18F]FDG uptake and blood flow estimated from the [15O]H2O component, requiring a full dynamic analysis of the two components, static images of [18F]FDG and the water components as well as [15O]H2O activation. It is shown that the resulting images and parametric values in ROIs are comparable to images obtained from separate imaging, illustrating the feasibility of simultaneous imaging of [18F]FDG and [15O]H2O components. For more information on this article, see medicalphysicsweb.org

Dynamic functional imaging of brain glucose utilization using fPET-FDG

DOE PAGES

Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; ...

2014-06-14

We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits themore » utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.« less

Patient motion effects on the quantification of regional myocardial blood flow with dynamic PET imaging.

PubMed

Hunter, Chad R R N; Klein, Ran; Beanlands, Rob S; deKemp, Robert A

2016-04-01

Patient motion is a common problem during dynamic positron emission tomography (PET) scans for quantification of myocardial blood flow (MBF). The purpose of this study was to quantify the prevalence of body motion in a clinical setting and evaluate with realistic phantoms the effects of motion on blood flow quantification, including CT attenuation correction (CTAC) artifacts that result from PET-CT misalignment. A cohort of 236 sequential patients was analyzed for patient motion under resting and peak stress conditions by two independent observers. The presence of motion, affected time-frames, and direction of motion was recorded; discrepancy between observers was resolved by consensus review. Based on these results, patient body motion effects on MBF quantification were characterized using the digital NURBS-based cardiac-torso phantom, with characteristic time activity curves (TACs) assigned to the heart wall (myocardium) and blood regions. Simulated projection data were corrected for attenuation and reconstructed using filtered back-projection. All simulations were performed without noise added, and a single CT image was used for attenuation correction and aligned to the early- or late-frame PET images. In the patient cohort, mild motion of 0.5 ± 0.1 cm occurred in 24% and moderate motion of 1.0 ± 0.3 cm occurred in 38% of patients. Motion in the superior/inferior direction accounted for 45% of all detected motion, with 30% in the superior direction. Anterior/posterior motion was predominant (29%) in the posterior direction. Left/right motion occurred in 24% of cases, with similar proportions in the left and right directions. Computer simulation studies indicated that errors in MBF can approach 500% for scans with severe patient motion (up to 2 cm). The largest errors occurred when the heart wall was shifted left toward the adjacent lung region, resulting in a severe undercorrection for attenuation of the heart wall. Simulations also indicated that the magnitude of MBF errors resulting from motion in the superior/inferior and anterior/posterior directions was similar (up to 250%). Body motion effects were more detrimental for higher resolution PET imaging (2 vs 10 mm full-width at half-maximum), and for motion occurring during the mid-to-late time-frames. Motion correction of the reconstructed dynamic image series resulted in significant reduction in MBF errors, but did not account for the residual PET-CTAC misalignment artifacts. MBF bias was reduced further using global partial-volume correction, and using dynamic alignment of the PET projection data to the CT scan for accurate attenuation correction during image reconstruction. Patient body motion can produce MBF estimation errors up to 500%. To reduce these errors, new motion correction algorithms must be effective in identifying motion in the left/right direction, and in the mid-to-late time-frames, since these conditions produce the largest errors in MBF, particularly for high resolution PET imaging. Ideally, motion correction should be done before or during image reconstruction to eliminate PET-CTAC misalignment artifacts.

Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50-MV photon radiation therapy.

PubMed

Janek Strååt, Sara; Jacobsson, Hans; Noz, Marilyn E; Andreassen, Björn; Näslund, Ingemar; Jonsson, Cathrine

2013-01-23

The purpose of this work was to reveal the research interest value of positron emission tomography (PET) imaging in visualizing the induced tissue activity post high-energy photon radiation treatment. More specifically, the focus was on the possibility of retrieving data such as tissue composition and physical half-lives from dynamic PET acquisitions, as positron-emitting radionuclides such as 15O, 11C, and 13N are produced in vivo during radiation treatment with high-energy photons (>15 MeV). The type, amount, and distribution of induced positron-emitting radionuclides depend on the irradiated tissue cross section, the photon spectrum, and the possible perfusion-driven washout. A 62-year-old man diagnosed with prostate cancer was referred for palliative radiation treatment of the pelvis minor. A total dose of 8 Gy was given using high-energy photon beams (50 MV) with a racetrack microtron, and 7 min after the end of irradiation, the patient was positioned in a PET/computed tomography (CT) camera, and a list-mode acquisition was performed for 30 min. Two volumes of interests (VOIs) were positioned on the dynamic PET/CT images, one in the urinary bladder and the other in the subcutaneous fat. Analysis of the measured relative count rate was performed in order to compute the tissue compositions and physical half-lives in the two regions. Dynamic analysis from the two VOIs showed that the decay constants of activated oxygen and carbon could be deduced. Calculation of tissue composition from analyzing the VOI containing subcutaneous fat only moderately agreed with that of the tabulated International Commission on Radiation Units & Measurements (ICRU) data of the adipose tissue. However, the same analysis for the bladder showed a good agreement with that of the tabulated ICRU data. PET can be used in visualizing the induced activity post high-energy photon radiation treatment. Despite the very low count rate in this specific application, wherein 7 min after treatment was about 5% of that of a standard 18F-FDG PET scan, the distribution of activated tissue elements (15O and 11C) could be calculated from the dynamic PET data. One possible future application of this method could possibly be to measure and determine the tumor tissue composition in order to identify any hypoxic or necrotic region, which is information that can be used in the ongoing therapy planning process. The official name of the trial committee of this study is 'Regionala etikprövningsnämnden i Stockholm' (FE 289, Stockholm, SE-17177, Sweden). The unique identifying number is 2011/1789-31/2.

Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications.

PubMed

Näslund, Olivia; Smits, Anja; Förander, Petter; Laesser, Mats; Bartek, Jiri; Gempt, Jens; Liljegren, Ann; Daxberg, Eva-Lotte; Jakola, Asgeir Store

2018-05-24

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83-100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters.

Non-invasive breast biopsy method using GD-DTPA contrast enhanced MRI series and F-18-FDG PET/CT dynamic image series

NASA Astrophysics Data System (ADS)

Magri, Alphonso William

This study was undertaken to develop a nonsurgical breast biopsy from Gd-DTPA Contrast Enhanced Magnetic Resonance (CE-MR) images and F-18-FDG PET/CT dynamic image series. A five-step process was developed to accomplish this. (1) Dynamic PET series were nonrigidly registered to the initial frame using a finite element method (FEM) based registration that requires fiducial skin markers to sample the displacement field between image frames. A commercial FEM package (ANSYS) was used for meshing and FEM calculations. Dynamic PET image series registrations were evaluated using similarity measurements SAVD and NCC. (2) Dynamic CE-MR series were nonrigidly registered to the initial frame using two registration methods: a multi-resolution free-form deformation (FFD) registration driven by normalized mutual information, and a FEM-based registration method. Dynamic CE-MR image series registrations were evaluated using similarity measurements, localization measurements, and qualitative comparison of motion artifacts. FFD registration was found to be superior to FEM-based registration. (3) Nonlinear curve fitting was performed for each voxel of the PET/CT volume of activity versus time, based on a realistic two-compartmental Patlak model. Three parameters for this model were fitted; two of them describe the activity levels in the blood and in the cellular compartment, while the third characterizes the washout rate of F-18-FDG from the cellular compartment. (4) Nonlinear curve fitting was performed for each voxel of the MR volume of signal intensity versus time, based on a realistic two-compartment Brix model. Three parameters for this model were fitted: rate of Gd exiting the compartment, representing the extracellular space of a lesion; rate of Gd exiting a blood compartment; and a parameter that characterizes the strength of signal intensities. Curve fitting used for PET/CT and MR series was accomplished by application of the Levenburg-Marquardt nonlinear regression algorithm. The best-fit parameters were used to create 3D parametric images. Compartmental modeling evaluation was based on the ability of parameter values to differentiate between tissue types. This evaluation was used on registered and unregistered image series and found that registration improved results. (5) PET and MR parametric images were registered through FEM- and FFD-based registration. Parametric image registration was evaluated using similarity measurements, target registration error, and qualitative comparison. Comparing FFD and FEM-based registration results showed that the FEM method is superior. This five-step process constitutes a novel multifaceted approach to a nonsurgical breast biopsy that successfully executes each step. Comparison of this method to biopsy still needs to be done with a larger set of subject data.

PET Imaging on Dynamic Metabolic Changes after Combination Therapy of Paclitaxel and the Traditional Chinese Medicine in Breast Cancer-Bearing Mice.

PubMed

Chen, Yao; Wang, Ling; Liu, Hao; Song, Fahuan; Xu, Caiyun; Zhang, Kai; Chen, Qing; Wu, Shuang; Zhu, Yunqi; Dong, Ying; Zhou, Min; Zhang, Hong; Tian, Mei

2018-04-01

The aim of the study was to non-invasively evaluate the anticancer activity of a traditional Chinese medicine-Huaier, combined with paclitaxel (PTX) in breast cancer bearing mice by detecting dynamic metabolic changes with positron emission tomography (PET). Balb/c nude mice were randomly divided into one of the four groups: Huaier, PTX, PTX + Huaier, or the control. PET imaging with 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) was performed to monitor the metabolic changes in BT474 (luminal B) and MDA-MB-231 (triple-negative) breast cancer xenografts. Immunohistochemistry (IHC) study was performed immediately after the final PET scan to assess the expressions of phosphatidylinositol 3-kinase (PI3K), phospho-AKT (p-AKT), caspase-3, and vascular endothelial growth factor (VEGF). Compared to the control group, [ 18 F]FDG accumulation demonstrated a significant decrease in PTX + Huaier (p < 0.01) or Huaier group (p < 0.05), which was consistent to the decreased expression of PI3K (p < 0.05) and p-AKT (p < 0.05) in the breast cancer xenografts. The therapeutic effect of Huaier combined with PTX was superior than the PTX alone in BT474 and MDA-MB-231 breast cancer-bearing mice. [ 18 F]FDG PET imaging could be a potential non-invasive approach to assess the metabolic changes after chemotherapy combined with traditional Chinese medicine in the breast cancer.

A comparison of pet and purpose-bred research dog (Canis familiaris) performance on human-guided object-choice tasks.

PubMed

Lazarowski, Lucia; Dorman, David C

2015-01-01

Several studies have shown that domestic dogs respond to human social cues such as pointing. Some experiments have shown that pet dogs outperformed wolves in following a momentary distal point. These findings have lent support to the hypothesis that domestication is responsible for domestic dogs' ability to utilize human gestures. Other studies demonstrating comparable performance in human-socialized wolves suggest this skill depends on experience with relevant human stimuli. However, domestic dogs lacking thorough exposure to humans are underrepresented in the comparative literature. The goal of this study was to evaluate pet and kennel-reared research domestic dogs on their ability to follow two types of point in an object-choice task. This study used young adult, intact male research dogs (n=11) and a comparison group of pet dogs living in human homes (n=9). We found that while pet dogs followed the momentary distal point above chance levels, research dogs did not. Both groups followed the simpler dynamic proximal point; however, pet dogs outperformed research dogs on this task. Our results indicate that ontogenetic experiences may influence a domestic dog's ability to use human gestures, highlighting the importance of testing different sub-populations of domestic dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

Relative equilibrium plot improves graphical analysis and allows bias correction of standardized uptake value ratio in quantitative 11C-PiB PET studies.

PubMed

Zhou, Yun; Sojkova, Jitka; Resnick, Susan M; Wong, Dean F

2012-04-01

Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies. The objective of this study was to use a recently developed relative equilibrium-based graphical (RE) plot method to improve and simplify the 2 commonly used methods for quantification of (11)C-Pittsburgh compound B ((11)C-PiB) PET. The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight (11)C-PiB dynamic PET scans (66 from controls and 12 from participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were defined on coregistered MR images. Both the ROI and the pixelwise time-activity curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI time-activity curves were used as a reference for comparison of DVR estimates. Results from the theoretic analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI time-activity curves. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, and cingulate regions and the striatum were underestimated by the Logan plot (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%; MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. The RE plot improves pixelwise quantification of (11)C-PiB dynamic PET, compared with the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of (11)C-PiB studies.

Relative equilibrium plot improves graphical analysis and allows bias correction of SUVR in quantitative [11C]PiB PET studies

PubMed Central

Zhou, Yun; Sojkova, Jitka; Resnick, Susan M.; Wong, Dean F.

2012-01-01

Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVR) in ligand-receptor dynamic PET studies. The objective of this study is to use a recently developed relative equilibrium-based graphical plot (RE plot) method to improve and simplify the two commonly used methods for quantification of [11C]PiB PET. Methods The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight [11C]PiB dynamic PET scans (66 from controls and 12 from mildly cognitively impaired participants (MCI) from the Baltimore Longitudinal Study of Aging (BLSA)) were acquired over 90 minutes. Regions of interest (ROIs) were defined on coregistered MRIs. Both the ROI and pixelwise time activity curves (TACs) were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI TACs were used as a reference for comparison of DVR estimates. Results Results from the theoretical analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI TACs. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, cingulate regions, and the striatum were underestimated by the Logan plot (controls 4 – 12%; MCI 9 – 16%) and overestimated by the SUVR (controls 8 – 16%; MCI 16 – 24%). This bias was higher in the MCI group than in controls (p < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. Conclusion The RE plot improves pixel-wise quantification of [11C]PiB dynamic PET compared to the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates compared to SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of [11C]PiB studies. PMID:22414634

Competitive Advantage of PET/MRI

PubMed Central

Jadvar, Hossein; Colletti, Patrick M.

2013-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. PMID:23791129

Competitive advantage of PET/MRI.

PubMed

Jadvar, Hossein; Colletti, Patrick M

2014-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A microvascular compartment model validated using 11C-methylglucose liver PET in pigs

NASA Astrophysics Data System (ADS)

Munk, Ole L.; Keiding, Susanne; Baker, Charles; Bass, Ludvik

2018-01-01

The standard compartment model (CM) is widely used to analyse dynamic PET data. The CM is fitted to time-activity curves to estimate rate constants that describe the transport of a tracer between well-mixed compartments. The aim of this study was to develop and validate a more realistic microvascular compartment model (MCM) that includes capillary tracer concentration gradients, backflux from cells into the perfused capillaries and multiple re-uptakes during the passage through a capillary. The MCM incorporates only parameters with clear physiological meaning, it is easy to implement, and it does not require numerical solution. We compared the MCM and CM for the analysis of 3 min dynamic PET data of pig livers (N  =  5) following injection of 11C-methylglucose. During PET scans, the tracer concentrations in blood were measured in the abdominal aorta, portal vein and liver vein by manual sampling. We found that the MCM outperformed the CM and that dynamic PET data include information which cannot be extracted using standard CM. The MCM fitted dynamic PET data better than the CM (Akaike values were 46  ±  4 for best MCM fits, and 82  ±  8 for best CM fits; mean  ±  standard deviation) and extracted physiologically reasonable parameter estimates such as blood perfusion that were in agreement with independent measurements. The difference between model-independent perfusion estimates and the best MCM perfusion estimates was  -0.01  ±  0.05 ml/ml/min, whereas the difference was 0.30  ±  0.13 ml/ml/min using the CM. In addition, the MCM predicted the time course of concentrations in the liver vein, a prediction fundamentally unobtainable using the CM as it does not return tracer backflux from cells to capillary blood. The results demonstrate the benefit of using models that include more physiology and that models including concentration gradients should be preferred when analysing the blood-cell exchange of any tracer in any capillary bed.

Positron emission tomography to assess hypoxia and perfusion in lung cancer

PubMed Central

Verwer, Eline E; Boellaard, Ronald; van der Veldt, Astrid AM

2014-01-01

In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed. PMID:25493221

Combining dynamic and ECG-gated ⁸²Rb-PET for practical implementation in the clinic.

PubMed

Sayre, George A; Bacharach, Stephen L; Dae, Michael W; Seo, Youngho

2012-01-01

For many cardiac clinics, list-mode PET is impractical. Therefore, separate dynamic and ECG-gated acquisitions are needed to detect harmful stenoses, indicate affected coronary arteries, and estimate stenosis severity. However, physicians usually order gated studies only because of dose, time, and cost limitations. These gated studies are limited to detection. In an effort to remove these limitations, we developed a novel curve-fitting algorithm [incomplete data (ICD)] to accurately calculate coronary flow reserve (CFR) from a combined dynamic-ECG protocol of a length equal to a typical gated scan. We selected several retrospective dynamic studies to simulate shortened dynamic acquisitions of the combined protocol and compared (a) the accuracy of ICD and a nominal method in extrapolating the complete functional form of arterial input functions (AIFs); and (b) the accuracy of ICD and ICD-AP (ICD with a-posteriori knowledge of complete-data AIFs) in predicting CFRs. According to the Akaike information criterion, AIFs predicted by ICD were more accurate than those predicted by the nominal method in 11 out of 12 studies. CFRs predicted by ICD and ICD-AP were similar to complete-data predictions (PICD=0.94 and PICD-AP=0.91) and had similar average errors (eICD=2.82% and eICD-AP=2.79%). According to a nuclear cardiologist and an expert analyst of PET data, both ICD and ICD-AP predicted CFR values with sufficient accuracy for the clinic. Therefore, by using our method, physicians in cardiac clinics would have access to the necessary amount of information to differentiate between single-vessel and triple-vessel disease for treatment decision making.

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

PubMed

Sachpekidis, C; Goldschmidt, H; Kopka, K; Kopp-Schneider, A; Dimitrakopoulou-Strauss, A

2018-04-10

Despite the significant upgrading in recent years of the role of 18 F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18 F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18 F-FDG PET/CT. Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18 F-FDG PET/CT and 18 F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18 F-FDG PET/CT demonstrated focal, 18 F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18 F-FLT PET/CT showed focal, 18 F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18 F-FDG avid, focal, MM-indicative lesions were detected with 18 F-FDG PET/CT, while 17 18 F-FLT avid, focal, MM-indicative lesions were detected with 18 F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18 F-FDG PET/CT than for 18 F-FLT PET/CT. A common finding was a mismatch of focally increased 18 F-FDG uptake and reduced 18 F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18 F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUV mean and SUV max were significantly higher for 18 F-FLT than for 18 F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers. Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that 18 F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

Parametric Methods for Dynamic 11C-Phenytoin PET Studies.

PubMed

Mansor, Syahir; Yaqub, Maqsood; Boellaard, Ronald; Froklage, Femke E; de Vries, Anke; Bakker, Esther D M; Voskuyl, Rob A; Eriksson, Jonas; Schwarte, Lothar A; Verbeek, Joost; Windhorst, Albert D; Lammertsma, Adriaan A

2017-03-01

In this study, the performance of various methods for generating quantitative parametric images of dynamic 11 C-phenytoin PET studies was evaluated. Methods: Double-baseline 60-min dynamic 11 C-phenytoin PET studies, including online arterial sampling, were acquired for 6 healthy subjects. Parametric images were generated using Logan plot analysis, a basis function method, and spectral analysis. Parametric distribution volume (V T ) and influx rate ( K 1 ) were compared with those obtained from nonlinear regression analysis of time-activity curves. In addition, global and regional test-retest (TRT) variability was determined for parametric K 1 and V T values. Results: Biases in V T observed with all parametric methods were less than 5%. For K 1 , spectral analysis showed a negative bias of 16%. The mean TRT variabilities of V T and K 1 were less than 10% for all methods. Shortening the scan duration to 45 min provided similar V T and K 1 with comparable TRT performance compared with 60-min data. Conclusion: Among the various parametric methods tested, the basis function method provided parametric V T and K 1 values with the least bias compared with nonlinear regression data and showed TRT variabilities lower than 5%, also for smaller volume-of-interest sizes (i.e., higher noise levels) and shorter scan duration. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Study of oxygen scavenging PET-based films activated by water

NASA Astrophysics Data System (ADS)

Rossi, Gabriella; Scarfato, Paola; Incarnato, Loredana

2016-05-01

In this work an active barrier system consisting of a thin and transparent film based on polyethylene terephthalate (PET) was studied. Dynamic oxygen absorption measurements were performed at different values of relative humidity and temperature, pointing out that humidity is a key factor in activating the oxidation of the polymer sample. Moreover, the thermal and optical properties of the films were investigated and a good correlation was found between the crystallinity increase and the consequent transparency reduction occurring after the oxygen absorption.

Methods for the correction of vascular artifacts in PET O-15 water brain-mapping studies

NASA Astrophysics Data System (ADS)

Chen, Kewei; Reiman, E. M.; Lawson, M.; Yun, Lang-sheng; Bandy, D.; Palant, A.

1996-12-01

While positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) can be used to map brain regions that are involved in normal and pathological human behaviors, measurements in the anteromedial temporal lobe can be confounded by the combined effects of radiotracer activity in neighboring arteries and partial-volume averaging. The authors now describe two simple methods to address this vascular artifact. One method utilizes the early frames of a dynamic PET study, while the other method utilizes a coregistered magnetic resonance image (MRI) to characterize the vascular region of interest (VROI). Both methods subsequently assign a common value to each pixel in the VROI for the control (baseline) scan and the activation scan. To study the vascular artifact and to demonstrate the ability of the proposed methods correcting the vascular artifact, four dynamic PET scans were performed in a single subject during the same behavioral state. For each of the four scans, a vascular scan containing vascular activity was computed as the summation of the images acquired 0-60 s after radiotracer administration, and a control scan containing minimal vascular activity was computed as the summation of the images acquired 20-80 s after radiotracer administration. t-score maps calculated from the four pairs of vascular and control scans were used to characterize regional blood flow differences related to vascular activity before and after the application of each vascular artifact correction method. Both methods eliminated the observed differences in vascular activity, as well as the vascular artifact observed in the anteromedial temporal lobes. Using PET data from a study of normal human emotion, these methods permitted the authors to identify rCBF increases in the anteromedial temporal lobe free from the potentially confounding, combined effects of vascular activity and partial-volume averaging.

TH-E-202-01: Pitfalls and Remedies in PET/CT Imaging for RT Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, T.

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy

NASA Astrophysics Data System (ADS)

Wangerin, Kristen A.; Muzi, Mark; Peterson, Lanell M.; Linden, Hannah M.; Novakova, Alena; Mankoff, David A.; E Kinahan, Paul

2017-05-01

We developed a method to evaluate variations in the PET imaging process in order to characterize the relative ability of static and dynamic metrics to measure breast cancer response to therapy in a clinical trial setting. We performed a virtual clinical trial by generating 540 independent and identically distributed PET imaging study realizations for each of 22 original dynamic fluorodeoxyglucose (18F-FDG) breast cancer patient studies pre- and post-therapy. Each noise realization accounted for known sources of uncertainty in the imaging process, such as biological variability and SUV uptake time. Four definitions of SUV were analyzed, which were SUVmax, SUVmean, SUVpeak, and SUV50%. We performed a ROC analysis on the resulting SUV and kinetic parameter uncertainty distributions to assess the impact of the variability on the measurement capabilities of each metric. The kinetic macro parameter, K i , showed more variability than SUV (mean CV K i   =  17%, SUV  =  13%), but K i pre- and post-therapy distributions also showed increased separation compared to the SUV pre- and post-therapy distributions (mean normalized difference K i   =  0.54, SUV  =  0.27). For the patients who did not show perfect separation between the pre- and post-therapy parameter uncertainty distributions (ROC AUC  <  1), dynamic imaging outperformed SUV in distinguishing metabolic change in response to therapy, ranging from 12 to 14 of 16 patients over all SUV definitions and uptake time scenarios (p  <  0.05). For the patient cohort in this study, which is comprised of non-high-grade ER+  tumors, K i outperformed SUV in an ROC analysis of the parameter uncertainty distributions pre- and post-therapy. This methodology can be applied to different scenarios with the ability to inform the design of clinical trials using PET imaging.

Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET.

PubMed

Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

2017-05-01

Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P < .001). Static fuzzy locally adaptive Bayesian (FLAB) volumes corresponded best with pathology volumes (intraclass correlation coefficient, 0.72; P < .001). Bland-Altman analyses showed the highest precision and accuracy for static FLAB volumes. Glucose metabolic rate and 18 F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas V B was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, 18 F-FDG phosphorylation rate, and V B were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static 18 F-FDG PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and V B between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. © RSNA, 2016 Online supplemental material is available for this article.

Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification.

PubMed

Wang, Shouyi; Bowen, Stephen R; Chaovalitwongse, W Art; Sandison, George A; Grabowski, Thomas J; Kinahan, Paul E

2014-02-21

The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUV(peak)) over lesions of interest. Relative differences in SUV(peak) between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUV(peak) values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion compensation when clinicians quantitatively assess PET/CT for therapy target definition and response assessment.

Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification

NASA Astrophysics Data System (ADS)

Wang, Shouyi; Bowen, Stephen R.; Chaovalitwongse, W. Art; Sandison, George A.; Grabowski, Thomas J.; Kinahan, Paul E.

2014-02-01

The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUVpeak) over lesions of interest. Relative differences in SUVpeak between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUVpeak values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion compensation when clinicians quantitatively assess PET/CT for therapy target definition and response assessment.

Comparison of quantitatively analyzed dynamic area-detector CT using various mathematic methods with FDG PET/CT in management of solitary pulmonary nodules.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Fujisawa, Yasuko; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Sugimura, Kazuro

2013-06-01

The objective of our study was to prospectively compare the capability of dynamic area-detector CT analyzed with different mathematic methods and PET/CT in the management of pulmonary nodules. Fifty-two consecutive patients with 96 pulmonary nodules underwent dynamic area-detector CT, PET/CT, and microbacterial or pathologic examinations. All nodules were classified into the following groups: malignant nodules (n = 57), benign nodules with low biologic activity (n = 15), and benign nodules with high biologic activity (n = 24). On dynamic area-detector CT, the total, pulmonary arterial, and systemic arterial perfusions were calculated using the dual-input maximum slope method; perfusion was calculated using the single-input maximum slope method; and extraction fraction and blood volume (BV) were calculated using the Patlak plot method. All indexes were statistically compared among the three nodule groups. Then, receiver operating characteristic analyses were used to compare the diagnostic capabilities of the maximum standardized uptake value (SUVmax) and each perfusion parameter having a significant difference between malignant and benign nodules. Finally, the diagnostic performances of the indexes were compared by means of the McNemar test. No adverse effects were observed in this study. All indexes except extraction fraction and BV, both of which were calculated using the Patlak plot method, showed significant differences among the three groups (p < 0.05). Areas under the curve of total perfusion calculated using the dual-input method, pulmonary arterial perfusion calculated using the dual-input method, and perfusion calculated using the single-input method were significantly larger than that of SUVmax (p < 0.05). The accuracy of total perfusion (83.3%) was significantly greater than the accuracy of the other indexes: pulmonary arterial perfusion (72.9%, p < 0.05), systemic arterial perfusion calculated using the dual-input method (69.8%, p < 0.05), perfusion (66.7%, p < 0.05), and SUVmax (60.4%, p < 0.05). Dynamic area-detector CT analyzed using the dual-input maximum slope method has better potential for the diagnosis of pulmonary nodules than dynamic area-detector CT analyzed using other methods and than PET/CT.

MR-guided dynamic PET reconstruction with the kernel method and spectral temporal basis functions

NASA Astrophysics Data System (ADS)

Novosad, Philip; Reader, Andrew J.

2016-06-01

Recent advances in dynamic positron emission tomography (PET) reconstruction have demonstrated that it is possible to achieve markedly improved end-point kinetic parameter maps by incorporating a temporal model of the radiotracer directly into the reconstruction algorithm. In this work we have developed a highly constrained, fully dynamic PET reconstruction algorithm incorporating both spectral analysis temporal basis functions and spatial basis functions derived from the kernel method applied to a co-registered T1-weighted magnetic resonance (MR) image. The dynamic PET image is modelled as a linear combination of spatial and temporal basis functions, and a maximum likelihood estimate for the coefficients can be found using the expectation-maximization (EM) algorithm. Following reconstruction, kinetic fitting using any temporal model of interest can be applied. Based on a BrainWeb T1-weighted MR phantom, we performed a realistic dynamic [18F]FDG simulation study with two noise levels, and investigated the quantitative performance of the proposed reconstruction algorithm, comparing it with reconstructions incorporating either spectral analysis temporal basis functions alone or kernel spatial basis functions alone, as well as with conventional frame-independent reconstruction. Compared to the other reconstruction algorithms, the proposed algorithm achieved superior performance, offering a decrease in spatially averaged pixel-level root-mean-square-error on post-reconstruction kinetic parametric maps in the grey/white matter, as well as in the tumours when they were present on the co-registered MR image. When the tumours were not visible in the MR image, reconstruction with the proposed algorithm performed similarly to reconstruction with spectral temporal basis functions and was superior to both conventional frame-independent reconstruction and frame-independent reconstruction with kernel spatial basis functions. Furthermore, we demonstrate that a joint spectral/kernel model can also be used for effective post-reconstruction denoising, through the use of an EM-like image-space algorithm. Finally, we applied the proposed algorithm to reconstruction of real high-resolution dynamic [11C]SCH23390 data, showing promising results.

MR-guided dynamic PET reconstruction with the kernel method and spectral temporal basis functions.

PubMed

Novosad, Philip; Reader, Andrew J

2016-06-21

Recent advances in dynamic positron emission tomography (PET) reconstruction have demonstrated that it is possible to achieve markedly improved end-point kinetic parameter maps by incorporating a temporal model of the radiotracer directly into the reconstruction algorithm. In this work we have developed a highly constrained, fully dynamic PET reconstruction algorithm incorporating both spectral analysis temporal basis functions and spatial basis functions derived from the kernel method applied to a co-registered T1-weighted magnetic resonance (MR) image. The dynamic PET image is modelled as a linear combination of spatial and temporal basis functions, and a maximum likelihood estimate for the coefficients can be found using the expectation-maximization (EM) algorithm. Following reconstruction, kinetic fitting using any temporal model of interest can be applied. Based on a BrainWeb T1-weighted MR phantom, we performed a realistic dynamic [(18)F]FDG simulation study with two noise levels, and investigated the quantitative performance of the proposed reconstruction algorithm, comparing it with reconstructions incorporating either spectral analysis temporal basis functions alone or kernel spatial basis functions alone, as well as with conventional frame-independent reconstruction. Compared to the other reconstruction algorithms, the proposed algorithm achieved superior performance, offering a decrease in spatially averaged pixel-level root-mean-square-error on post-reconstruction kinetic parametric maps in the grey/white matter, as well as in the tumours when they were present on the co-registered MR image. When the tumours were not visible in the MR image, reconstruction with the proposed algorithm performed similarly to reconstruction with spectral temporal basis functions and was superior to both conventional frame-independent reconstruction and frame-independent reconstruction with kernel spatial basis functions. Furthermore, we demonstrate that a joint spectral/kernel model can also be used for effective post-reconstruction denoising, through the use of an EM-like image-space algorithm. Finally, we applied the proposed algorithm to reconstruction of real high-resolution dynamic [(11)C]SCH23390 data, showing promising results.

TU-G-BRA-02: Can We Extract Lung Function Directly From 4D-CT Without Deformable Image Registration?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kipritidis, J; Woodruff, H; Counter, W

Purpose: Dynamic CT ventilation imaging (CT-VI) visualizes air volume changes in the lung by evaluating breathing-induced lung motion using deformable image registration (DIR). Dynamic CT-VI could enable functionally adaptive lung cancer radiation therapy, but its sensitivity to DIR parameters poses challenges for validation. We hypothesize that a direct metric using CT parameters derived from Hounsfield units (HU) alone can provide similar ventilation images without DIR. We compare the accuracy of Direct and Dynamic CT-VIs versus positron emission tomography (PET) images of inhaled {sup 68}Ga-labelled nanoparticles (‘Galligas’). Methods: 25 patients with lung cancer underwent Galligas 4D-PET/CT scans prior to radiation therapy.more » For each patient we produced three CT- VIs. (i) Our novel method, Direct CT-VI, models blood-gas exchange as the product of air and tissue density at each lung voxel based on time-averaged 4D-CT HU values. Dynamic CT-VIs were produced by evaluating: (ii) regional HU changes, and (iii) regional volume changes between the exhale and inhale 4D-CT phase images using a validated B-spline DIR method. We assessed the accuracy of each CT-VI by computing the voxel-wise Spearman correlation with free-breathing Galligas PET, and also performed a visual analysis. Results: Surprisingly, Direct CT-VIs exhibited better global correlation with Galligas PET than either of the dynamic CT-VIs. The (mean ± SD) correlations were (0.55 ± 0.16), (0.41 ± 0.22) and (0.29 ± 0.27) for Direct, Dynamic HU-based and Dynamic volume-based CT-VIs respectively. Visual comparison of Direct CT-VI to PET demonstrated similarity for emphysema defects and ventral-to-dorsal gradients, but inability to identify decreased ventilation distal to tumor-obstruction. Conclusion: Our data supports the hypothesis that Direct CT-VIs are as accurate as Dynamic CT-VIs in terms of global correlation with Galligas PET. Visual analysis, however, demonstrated that different CT-VI algorithms might have varying accuracy depending on the underlying cause of ventilation abnormality. This research was supported by a National Health and Medical Research Council (NHMRC) Australia Fellowship, an Cancer Institute New South Wales Early Career Fellowship 13-ECF-1/15 and NHMRC scholarship APP1038399. No commercial funding was received for this work.« less

11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy.

PubMed

Arentson-Lantz, Emily J; Saeed, Isra H; Frassetto, Lynda A; Masharani, Umesh; Harnish, Roy J; Seo, Youngho; VanBrocklin, Henry F; Hawkins, Randall A; Mari-Aparici, Carina; Pampaloni, Miguel H; Slater, James; Paddon-Jones, Douglas; Lang, Thomas F

2017-05-01

The objective of this study was to determine if clinical dynamic PET/CT imaging with 11 C-L-methyl-methionine ( 11 C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13 C 6 ] phenylalanine ( 13 C 6 -Phe). Healthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11 C-MET and a stable isotope infusion of 13 C 6 -Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient K i from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle. Post-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both K i (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min -1 , p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in K i and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015). Dynamic PET/CT imaging with 11 C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11 C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

Spectral Clustering Predicts Tumor Tissue Heterogeneity Using Dynamic 18F-FDG PET: A Complement to the Standard Compartmental Modeling Approach.

PubMed

Katiyar, Prateek; Divine, Mathew R; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Schölkopf, Bernhard; Pichler, Bernd J; Disselhorst, Jonathan A

2017-04-01

In this study, we described and validated an unsupervised segmentation algorithm for the assessment of tumor heterogeneity using dynamic 18 F-FDG PET. The aim of our study was to objectively evaluate the proposed method and make comparisons with compartmental modeling parametric maps and SUV segmentations using simulations of clinically relevant tumor tissue types. Methods: An irreversible 2-tissue-compartmental model was implemented to simulate clinical and preclinical 18 F-FDG PET time-activity curves using population-based arterial input functions (80 clinical and 12 preclinical) and the kinetic parameter values of 3 tumor tissue types. The simulated time-activity curves were corrupted with different levels of noise and used to calculate the tissue-type misclassification errors of spectral clustering (SC), parametric maps, and SUV segmentation. The utility of the inverse noise variance- and Laplacian score-derived frame weighting schemes before SC was also investigated. Finally, the SC scheme with the best results was tested on a dynamic 18 F-FDG measurement of a mouse bearing subcutaneous colon cancer and validated using histology. Results: In the preclinical setup, the inverse noise variance-weighted SC exhibited the lowest misclassification errors (8.09%-28.53%) at all noise levels in contrast to the Laplacian score-weighted SC (16.12%-31.23%), unweighted SC (25.73%-40.03%), parametric maps (28.02%-61.45%), and SUV (45.49%-45.63%) segmentation. The classification efficacy of both weighted SC schemes in the clinical case was comparable to the unweighted SC. When applied to the dynamic 18 F-FDG measurement of colon cancer, the proposed algorithm accurately identified densely vascularized regions from the rest of the tumor. In addition, the segmented regions and clusterwise average time-activity curves showed excellent correlation with the tumor histology. Conclusion: The promising results of SC mark its position as a robust tool for quantification of tumor heterogeneity using dynamic PET studies. Because SC tumor segmentation is based on the intrinsic structure of the underlying data, it can be easily applied to other cancer types as well. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

PubMed

Renaud, Jennifer M; Yip, Kathy; Guimond, Jean; Trottier, Mikaël; Pibarot, Philippe; Turcotte, Eric; Maguire, Conor; Lalonde, Lucille; Gulenchyn, Karen; Farncombe, Troy; Wisenberg, Gerald; Moody, Jonathan; Lee, Benjamin; Port, Steven C; Turkington, Timothy G; Beanlands, Rob S; deKemp, Robert A

2017-01-01

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82 Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. 82 Rb or 13 N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics

NASA Astrophysics Data System (ADS)

Boutchko, Rostyslav; Rayz, Vitaliy L.; Vandehey, Nicholas T.; O'Neil, James P.; Budinger, Thomas F.; Nico, Peter S.; Druhan, Jennifer L.; Saloner, David A.; Gullberg, Grant T.; Moses, William W.

2012-01-01

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics.

PubMed

Boutchko, Rostyslav; Rayz, Vitaliy L; Vandehey, Nicholas T; O'Neil, James P; Budinger, Thomas F; Nico, Peter S; Druhan, Jennifer L; Saloner, David A; Gullberg, Grant T; Moses, William W

2012-01-01

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18 F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99m Tc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

Replacing climatological potential evapotranspiration estimates with dynamic satellite-based observations in operational hydrologic prediction models

NASA Astrophysics Data System (ADS)

Franz, K. J.; Bowman, A. L.; Hogue, T. S.; Kim, J.; Spies, R.

2011-12-01

In the face of a changing climate, growing populations, and increased human habitation in hydrologically risky locations, both short- and long-range planners increasingly require robust and reliable streamflow forecast information. Current operational forecasting utilizes watershed-scale, conceptual models driven by ground-based (commonly point-scale) observations of precipitation and temperature and climatological potential evapotranspiration (PET) estimates. The PET values are derived from historic pan evaporation observations and remain static from year-to-year. The need for regional dynamic PET values is vital for improved operational forecasting. With the advent of satellite remote sensing and the adoption of a more flexible operational forecast system by the National Weather Service, incorporation of advanced data products is now more feasible than in years past. In this study, we will test a previously developed satellite-derived PET product (UCLA MODIS-PET) in the National Weather Service forecast models and compare the model results to current methods. The UCLA MODIS-PET method is based on the Priestley-Taylor formulation, is driven with MODIS satellite products, and produces a daily, 250m PET estimate. The focus area is eight headwater basins in the upper Midwest U.S. There is a need to develop improved forecasting methods for this region that are able to account for climatic and landscape changes more readily and effectively than current methods. This region is highly flood prone yet sensitive to prolonged dry periods in late summer and early fall, and is characterized by a highly managed landscape, which has drastically altered the natural hydrologic cycle. Our goal is to improve model simulations, and thereby, the initial conditions prior to the start of a forecast through the use of PET values that better reflect actual watershed conditions. The forecast models are being tested in both distributed and lumped mode.

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Positron emission tomography imaging of braintumors with Cobalt-55 and L-[1-C11]-tyrosine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansen, H.M.L.; Pruim J.; Willemsen, A.T.M.

1994-05-01

The applicability of positron emission tomography (PET) with [C-11] tyrosine (TYR) and Cobalt-55 (Co) in patients with known primary brain tumors is reported. We used Co as a Calcium (Ca) marker to study Ca influx in degenerating neural tissue and TYR to indicate incorporation of amino acids into protein. Four patients showing a primary brain tumor with central necrosis on CT/MRI were studied with Co-PET. Additionally, 2 of these patients were consecutively studied with TYR-PET. Diagnostic confirmation was obtained by means of histology and/or cytology shortly after PET. Thirty-seven MBq Co was administered iv. approximately 24 hours before acquisition. Themore » Co-scan was acquired for I hour. Immediately following Co-PET, 2 patients received 370 MBq TYR iv. TYR-PET acquisition was done dynamically for 55 minutes starting from the time of injection. The necrotic center of the tumor revealed no uptake of either Co or TYR. Vital tumor tissue showed intense uptake of TYR, indicating a high protein synthesis rate (PSR). The circumferent zone between necrotic and tumor tissue showed evident uptake of Co, suggesting cell-decay. In conclusion, TYR and Co are both suitable tracers for visualization of different aspects of brain malignancies, ie. PSR and cell-decay. Combining Co and TYR enables differentiation of necrosis vs. tumor growth with clear marking of the border zone. We think these complementary PET-techniques in conjunction with CT and/or MRI allow the visualization of different aspects of tumor tissue: central necrosis (CT/MRI), cell-decay (Co-PET) and vital tumor tissue (TYR-PET).« less

Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

NASA Astrophysics Data System (ADS)

Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

2013-12-01

In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

Methodologic Considerations for Quantitative 18F-FDG PET/CT Studies of Hepatic Glucose Metabolism in Healthy Subjects.

PubMed

Trägårdh, Malene; Møller, Niels; Sørensen, Michael

2015-09-01

PET with the glucose analog (18)F-FDG is used to measure regional tissue metabolism of glucose. However, (18)F-FDG may have affinities different from those of glucose for plasma membrane transporters and intracellular enzymes; the lumped constant (LC) can be used to correct these differences kinetically. The aims of this study were to investigate the feasibility of measuring human hepatic glucose metabolism with dynamic (18)F-FDG PET/CT and to determine an operational LC for (18)F-FDG by comparison with (3)H-glucose measurements. Eight healthy human subjects were included. In all studies, (18)F-FDG and (3)H-glucose were mixed in saline and coadministered. A 60-min dynamic PET recording of the liver was performed for 180 min with blood sampling from catheters in a hepatic vein and a radial artery (concentrations of (18)F-FDG and (3)H-glucose in blood). Hepatic blood flow was determined by indocyanine green infusion. First, 3 subjects underwent studies comparing bolus administration and constant-infusion administration of tracers during hyperinsulinemic-euglycemic clamping. Next, 5 subjects underwent studies comparing fasting and hyperinsulinemic-euglycemic clamping with tracer infusions. Splanchnic extraction fractions of (18)F-FDG (E*) and (3)H-glucose (E) were calculated from concentrations in blood, and the LC was calculated as ln(1 - E*)/ln(1 - E). Volumes of interest were drawn in the liver tissue, and hepatic metabolic clearance of (18)F-FDG (mL of blood/100 mL of liver tissue/min) was estimated. For bolus versus infusion, E* values were always negative when (18)F-FDG was administered as a bolus and were always positive when it was administered as an infusion. For fasting versus clamping, E* values were positive in 4 of 5 studies during fasting and were always positive during clamping. Negative extraction fractions were ascribed to the tracer distribution in the large volume of distribution in the prehepatic splanchnic bed. The LC ranged from 0.43 to 2.53, with no significant difference between fasting and clamping. The large volume of distribution of (18)F-FDG in the prehepatic splanchnic bed may complicate the analysis of dynamic PET data because it represents the mixed tracer input to the liver via the portal vein. Therefore, dynamic (18)F-FDG data for human hepatic glucose metabolism should be interpreted with caution, but constant tracer infusion seems to yield more robust results than bolus injection. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1992-07-01

The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of datamore » generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, [{sup 11}C]TRB (muscarinic), [{sup 11}C]flumazenil (benzodiazepine), [{sup 18}F]GBR12909, (dopamine), and [{sup 11}C]NMPB (muscarinic).« less

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1992-01-01

The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of datamore » generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, ({sup 11}C)TRB (muscarinic), ({sup 11}C)flumazenil (benzodiazepine), ({sup 18}F)GBR12909, (dopamine), and ({sup 11}C)NMPB (muscarinic).« less

Estimation of radiation dose to patients from (18) FDG whole body PET/CT investigations using dynamic PET scan protocol.

PubMed

Kaushik, Aruna; Jaimini, Abhinav; Tripathi, Madhavi; D'Souza, Maria; Sharma, Rajnish; Mondal, Anupam; Mishra, Anil K; Dwarakanath, Bilikere S

2015-12-01

There is a growing concern over the radiation exposure of patients from undergoing 18FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography) whole body investigations. The aim of the present study was to study the kinetics of 18FDG distributions and estimate the radiation dose received by patients undergoing 18FDG whole body PET/CT investigations. Dynamic PET scans in different regions of the body were performed in 49 patients so as to measure percentage uptake of 18FDG in brain, liver, spleen, adrenals, kidneys and stomach. The residence time in these organs was calculated and radiation dose was estimated using OLINDA software. The radiation dose from the CT component was computed using the software CT-Expo and measured using computed tomography dose index (CTDI) phantom and ionization chamber. As per the clinical protocol, the patients were refrained from eating and drinking for a minimum period of 4 h prior to the study. The estimated residence time in males was 0.196 h (brain), 0.09 h (liver), 0.007 h (spleen), 0.0006 h (adrenals), 0.013 h (kidneys) and 0.005 h (stomach) whereas it was 0.189 h (brain), 0.11 h (liver), 0.01 h (spleen), 0.0007 h (adrenals), 0.02 h (kidneys) and 0.004 h (stomach) in females. The effective dose was found to be 0.020 mSv/MBq in males and 0.025 mSv/MBq in females from internally administered 18FDG and 6.8 mSv in males and 7.9 mSv in females from the CT component. For an administered activity of 370 MBq of 18FDG, the effective dose from PET/CT investigations was estimated to be 14.2 mSv in males and 17.2 mSv in females. The present results did not demonstrate significant difference in the kinetics of 18FDG distribution in male and female patients. The estimated PET/CT doses were found to be higher than many other conventional diagnostic radiology examinations suggesting that all efforts should be made to clinically justify and carefully weigh the risk-benefit ratios prior to every 18FDG whole body PET/CT scan.

Simultaneous emission and transmission scanning in PET oncology: the effect on parameter estimation

NASA Astrophysics Data System (ADS)

Meikle, S. R.; Eberl, S.; Hooper, P. K.; Fulham, M. J.

1997-02-01

The authors investigated potential sources of bias due to simultaneous emission and transmission (SET) scanning and their effect on parameter estimation in dynamic positron emission tomography (PET) oncology studies. The sources of bias considered include: i) variation in transmission spillover (into the emission window) throughout the field of view, ii) increased scatter arising from rod sources, and iii) inaccurate deadtime correction. Net bias was calculated as a function of the emission count rate and used to predict distortion in [/sup 18/F]2-fluoro-2-deoxy-D-glucose (FDG) and [/sup 11/C]thymidine tissue curves simulating the normal liver and metastatic involvement of the liver. The effect on parameter estimates was assessed by spectral analysis and compartmental modeling. The various sources of bias approximately cancel during the early part of the study when count rate is maximal. Scatter dominates in the latter part of the study, causing apparently decreased tracer clearance which is more marked for thymidine than for FDG. The irreversible disposal rate constant, K/sub i/, was overestimated by <10% for FDG and >30% for thymidine. The authors conclude that SET has a potential role in dynamic FDG PET but is not suitable for /sup 11/C-labeled compounds.

Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET

PubMed Central

Swiercz, Rafal; Chiguru, Srinivas; Tahmasbi, Amir; Ramezani, Saleh M.; Hao, Guiyang; Challa, Dilip K.; Lewis, Matthew A.; Kulkarni, Padmakar V.; Sun, Xiankai; Ober, Raimund J.; Mason, Ralph P.; Ward, E. Sally

2015-01-01

Despite promise for the use of antibodies as molecular imaging agents in PET, their long in vivo half-lives result in poor contrast and radiation damage to normal tissue. This study describes an approach to overcome these limitations. Methods Mice bearing human epidermal growth factor receptor type 2 (HER2)–overexpressing tumors were injected with radiolabeled (124I, 125I) HER2-specific antibody (pertuzumab). Pertuzumab injection was followed 8 h later by the delivery of an engineered, antibody-based inhibitor of the receptor, FcRn. Biodistribution analyses and PET were performed at 24 and 48 h after pertuzumab injection. Results The delivery of the engineered, antibody-based FcRn inhibitor (or Abdeg, for antibody that enhances IgG degradation) results in improved tumor-to-blood ratios, reduced systemic exposure to radiolabel, and increased contrast during PET. Conclusion Abdegs have considerable potential as agents to stringently regulate antibody dynamics in vivo, resulting in increased contrast during molecular imaging with PET. PMID:24868106

Surface characterization and free thyroid hormones response of chemically modified poly(ethylene terephthalate) blood collection tubes

NASA Astrophysics Data System (ADS)

Jalali Dil, Ebrahim; Kim, Samuel C.; Saffar, Amir; Ajji, Abdellah; Zare, Richard N.; Sattayapiwat, Annie; Esguerra, Vanessa; Bowen, Raffick A. R.

2018-06-01

The surface chemistry and surface energy of chemically modified polyethylene terephthalate (PET) blood collection tubes (BCTs) were studied and the results showed a significant increase in hydrophilicity and polarity of modified PET surface. The surface modification created nanometer-sized, needle-like asperities through molecular segregation at the surface. The surface dynamics of the modified PET was examined by tracking its surface properties over a 280-day period. The results showed surface rearrangement toward a surface with lower surface energy and fewer nanometer-sized asperities. Thromboelastography (TEG) was used to evaluate and compare the thrombogenicity of the inner walls of various types of BCTs. The TEG tracings and data from various types of BCTs demonstrated differences in the reactionand coagulation times but not in clot strength. The performance of the modified tubes in free triiodothyronine (FT3) and free thyroxine (FT4) hormone tests was examined, and it was found that the interference of modified PET tubes was negligible compared to that of commercially available PET BCTs.

Evaluation of a short dynamic 18F-fluoride PET/CT scanning method to assess bone metabolic activity in spinal orthopedics.

PubMed

Peters, Marloes J M; Wierts, Roel; Jutten, Elisabeth M C; Halders, Servé G E A; Willems, Paul C P H; Brans, Boudewijn

2015-11-01

A complication after spinal fusion surgery is pseudarthrosis, but its radiological diagnosis is of limited value. (18)F-fluoride PET with its ability to assess bone metabolism activity could be of value. The goal of this study was to assess the clinical feasibility of calculating the static standardized uptake value (SUV) from a short dynamic scan without the use of blood sampling, thereby obtaining all dynamic and static parameters in a scan of only 30 min. This approach was tested on a retrospective patient population with persisting pain after spinal fusion surgery. In 16 patients, SUVs (SUV max, SUV mean) and kinetic parameters (K 1, k 2, k 3, v b, K i,NLR, K 1/k 2, k 3/(k 2 + k 3), K i,patlak) were derived from static and dynamic PET/CT scans of operated and control regions of the spine, after intravenous administration of 156-214 MBq (18)F-fluoride. Parameter differences between control and operated regions, as well as between pseudarthrosis and fused segments were evaluated. SUVmean at 30 and 60 min was calculated from kinetic parameters obtained from the dynamic data set (SUV mean,2TCM). Agreement between measured and calculated SUVs was evaluated through Bland-Altman plots. Overall, statistically significant differences between control and operated regions were observed for SUV max, SUV mean, K i,NLR, K i,patlak, K 1/k 2 and k 3/(k 2 + k 3). Diagnostic CT showed pseudarthrosis in 6/16 patients, while in 10/16 patients, segments were fused. Of all parameters, only those regarding the incorporation of bone [K i,NLR, K i,patlak, k 3/(k 2 + k 3)] differed statistically significant in the intervertebral disc space between the pseudarthrosis and fused patients group. The mean values of the patient-specific blood clearance rate [Formula: see text] differed statistically significant between the pseudarthrosis and the fusion group, with a p value of 0.011. This may correspond with the lack of statistical significance of the SUV values between pseudarthrosis and fused patients. Bland-Altman plots show that calculated SUV mean,2TCM values corresponded well with the measured SUV mean values. This study shows the feasibility of a 30-min dynamic (18)F-fluoride PET/CT scanning and this may provide dynamic parameters clinically relevant to the diagnosis of pseudarthrosis.

Reproducibility of functional volume and activity concentration in 18F-FDG PET/CT of liver metastases in colorectal cancer.

PubMed

Heijmen, Linda; de Geus-Oei, Lioe-Fee; de Wilt, Johannes H W; Visvikis, Dimitris; Hatt, Mathieu; Visser, Eric P; Bussink, Johan; Punt, Cornelis J A; Oyen, Wim J G; van Laarhoven, Hanneke W M

2012-12-01

Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before (18)F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of (18)F-FDG PET in colorectal liver metastases. Twenty patients scheduled for liver metastasectomy underwent two (18)F-FDG PET scans within 1 week. Bland-Altman analysis was performed to assess repeatability of SUV(max), SUV(mean), volume and TLG. Tumours were delineated using an adaptive threshold method (PET(SBR)) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method. Coefficient of repeatability of SUV(max) and SUV(mean) were ∼39 and ∼31 %, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET(SBR), from coefficients of repeatability of over 85 % to 45 % and 57 % for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV(mean). Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with (18)F-FDG PET parameters. In conclusion, repeatability of SUV(mean) and SUV(max) was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when (18)F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements, for instance by dynamic PET scanning protocols, is probably necessary to effectively use PET for early response monitoring.

68Ga-PSMA PET/MR-Positive, Histopathology-Proven Prostate Cancer in a Patient With Negative Multiparametric Prostate MRI.

PubMed

Muehlematter, Urs J; Rupp, Niels J; Mueller, Julian; Eberli, Daniel; Burger, Irene A

2018-05-25

Multiparametric MRI incorporating T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced sequences is currently used for detection and localization of clinically important prostate cancer (PCa). The Ga-labeled PET tracer targeting the prostate-specific membrane antigen (PSMA, Ga-PSMA-11) is a promising diagnostic approach for staging and restating PCa. Recent studies suggest that Ga-PSMA could also be used for primary PCa detection and localization. We report a case of a Ga-PSMA PET/MR-positive lesion of the peripheral zone in a 73-year-old man with a negative preceding multiparametric MRI. Radical prostatectomy and subsequent histopathologic examination confirmed a Gleason 4 + 4 PCa.

Physical and mechanical properties of mortars containing PET and PC waste aggregates.

PubMed

Hannawi, Kinda; Kamali-Bernard, Siham; Prince, William

2010-11-01

Non-biodegradable plastic aggregates made of polycarbonate (PC) and polyethylene terephthalate (PET) waste are used as partial replacement of natural aggregates in mortar. Various volume fractions of sand 3%, 10%, 20% and 50% are replaced by the same volume of plastic. This paper investigates the physical and mechanical properties of the obtained composites. The main results of this study show the feasibility of the reuse of PC and PET waste aggregates materials as partial volume substitutes for natural aggregates in cementitious materials. Despite of some drawbacks like a decrease in compressive strength, the use of PC and PET waste aggregates presents various advantages. A reduction of the specific weight of the cementitious materials and a significant improvement of their post-peak flexural behaviour are observed. The calculated flexural toughness factors increase significantly with increasing volume fraction of PET and PC-aggregates. Thus, addition of PC and PET plastic aggregates in cementitious materials seems to give good energy absorbing materials which is very interesting for several civil engineering applications like structures subjected to dynamic or impact efforts. The present study has shown quite encouraging results and opened new way for the recycling of PC waste aggregate in cement and concrete composites. Copyright © 2010 Elsevier Ltd. All rights reserved.

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction

NASA Astrophysics Data System (ADS)

Lüdemann, L.; Sreenivasa, G.; Michel, R.; Rosner, C.; Plotkin, M.; Felix, R.; Wust, P.; Amthauer, H.

2006-06-01

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 ± 52.0%) and lower partition coefficients (-31.6 ± 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

WE-G-BRD-06: Variation in Dynamic Positron Emission Tomography Imaging of Tumor Hypoxia in Early Stage Non-Small Cell Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelada, O; Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg; Decker, R

2014-06-15

Purpose: Tumor hypoxia is correlated with treatment failure. To date, there are no published studies investigating hypoxia in non-small cell lung cancer (NSCLC) patients undergoing SBRT. We aim to use 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET) imaging to non-invasively quantify the tumor hypoxic volume (HV), to elucidate potential roles of reoxygenation and tumor vascular response at high doses, and to identify an optimal prognostic imaging time-point. Methods: SBRT-eligible patients with NSCLC tumors >1cm were prospectively enrolled in an IRB-approved study. Computed Tomography and dynamic PET images (0–120min, 150–180min, and 210–240min post-injection) were acquired using a Siemens BiographmCT PET/CT scanner. 18F-FMISOmore » PET was performed on a single patient at 3 different time points around a single SBRT delivery of 18 Gy and HVs were compared using a tumor-to-blood ratio (TBR)>1.2 and rate of influx (Ki)>0.0015 (Patlak). Results: Results from our first patient showed substantial temporal changes in HV following SBRT. Using a TBR threshold >1.2 and summed images 210–240min, the HVs were 19%, 31% and 13% of total tumor volume on day 0, 2 (48 hours post-SBRT), and 4 (96 hours post-SBRT). The absolute volume of hypoxia increased by nearly a factor of 2 after 18 Gy and then decreased almost to baseline 96 hours later. Selected imaging timepoints resulted in temporal changes in HV quantification obtained with TBR. Ki, calculated using 4-hour dynamic data, evaluated HVs as 22%, 75% and 21%, respectively. Conclusions: ith the results of only one patient, this novel pilot study highlights the potential benefit of 18F-FMISO PET imaging as results indicate substantial temporal changes in tumor HV post-SBRT. Analysis suggests that TBR is not a robust parameter for accurate HV quantification and heavily influenced by imaging timepoint selection. Kinetic modeling parameters are more sensitive and may aid in future treatment individualization based on patient-specific biological information.« less

Monte Carlo simulation of efficient data acquisition for an entire-body PET scanner

NASA Astrophysics Data System (ADS)

Isnaini, Ismet; Obi, Takashi; Yoshida, Eiji; Yamaya, Taiga

2014-07-01

Conventional PET scanners can image the whole body using many bed positions. On the other hand, an entire-body PET scanner with an extended axial FOV, which can trace whole-body uptake images at the same time and improve sensitivity dynamically, has been desired. The entire-body PET scanner would have to process a large amount of data effectively. As a result, the entire-body PET scanner has high dead time at a multiplex detector grouping process. Also, the entire-body PET scanner has many oblique line-of-responses. In this work, we study an efficient data acquisition for the entire-body PET scanner using the Monte Carlo simulation. The simulated entire-body PET scanner based on depth-of-interaction detectors has a 2016-mm axial field-of-view (FOV) and an 80-cm ring diameter. Since the entire-body PET scanner has higher single data loss than a conventional PET scanner at grouping circuits, the NECR of the entire-body PET scanner decreases. But, single data loss is mitigated by separating the axially arranged detector into multiple parts. Our choice of 3 groups of axially-arranged detectors has shown to increase the peak NECR by 41%. An appropriate choice of maximum ring difference (MRD) will also maintain the same high performance of sensitivity and high peak NECR while at the same time reduces the data size. The extremely-oblique line of response for large axial FOV does not contribute much to the performance of the scanner. The total sensitivity with full MRD increased only 15% than that with about half MRD. The peak NECR was saturated at about half MRD. The entire-body PET scanner promises to provide a large axial FOV and to have sufficient performance values without using the full data.

Test-retest repeatability of myocardial oxidative metabolism and efficiency using standalone dynamic 11C-acetate PET and multimodality approaches in healthy controls.

PubMed

Hansson, Nils Henrik; Harms, Hendrik Johannes; Kim, Won Yong; Nielsen, Roni; Tolbod, Lars P; Frøkiær, Jørgen; Bouchelouche, Kirsten; Poulsen, Steen Hvitfeldt; Wiggers, Henrik; Parner, Erik Thorlund; Sörensen, Jens

2018-05-31

Myocardial efficiency measured by 11 C-acetate positron emission tomography (PET) has successfully been used in clinical research to quantify mechanoenergetic coupling. The objective of this study was to establish the repeatability of myocardial external efficiency (MEE) and work metabolic index (WMI) by non-invasive concepts. Ten healthy volunteers (63 ± 4 years) were examined twice, one week apart, using 11 C-acetate PET, cardiovascular magnetic resonance (CMR), and echocardiography. Myocardial oxygen consumption from PET was combined with stroke work data from CMR, echocardiography, or PET to obtain MEE and WMI for each modality. Repeatability was estimated as the coefficient of variation (CV) between test and retest. MEE CMR , MEE Echo , and MEE PET values were 21.9 ± 2.7%, 16.4 ± 3.7%, and 23.8 ± 4.9%, respectively, P < .001. WMI CMR , WMI Echo , and WMI PET values were 4.42 ± 0.90, 4.07 ± 0.63, and 4.58 ± 1.13 mmHg × mL/m 2  × 10 6 , respectively, P = .45. Repeatability for MEE CMR was superior compared with MEE Echo but did not differ significantly compared with MEE PET (6.3% vs 12.9% and 9.4%, P = .04 and .25). CV values for WMI CMR , WMI Echo , and WMI PET were 10.0%, 14.8%, and 12.0%, respectively, (P = .53). Non-invasive measurements of MEE using 11 C-acetate PET are highly repeatable. A PET-only approach did not differ significantly from CMR/PET and might facilitate further clinical research due to lower costs and broader applicability.

Reproducibility of Quantitative Brain Imaging Using a PET-Only and a Combined PET/MR System

PubMed Central

Lassen, Martin L.; Muzik, Otto; Beyer, Thomas; Hacker, Marcus; Ladefoged, Claes Nøhr; Cal-González, Jacobo; Wadsak, Wolfgang; Rausch, Ivo; Langer, Oliver; Bauer, Martin

2017-01-01

The purpose of this study was to test the feasibility of migrating a quantitative brain imaging protocol from a positron emission tomography (PET)-only system to an integrated PET/MR system. Potential differences in both absolute radiotracer concentration as well as in the derived kinetic parameters as a function of PET system choice have been investigated. Five healthy volunteers underwent dynamic (R)-[11C]verapamil imaging on the same day using a GE-Advance (PET-only) and a Siemens Biograph mMR system (PET/MR). PET-emission data were reconstructed using a transmission-based attenuation correction (AC) map (PET-only), whereas a standard MR-DIXON as well as a low-dose CT AC map was applied to PET/MR emission data. Kinetic modeling based on arterial blood sampling was performed using a 1-tissue-2-rate constant compartment model, yielding kinetic parameters (K1 and k2) and distribution volume (VT). Differences for parametric values obtained in the PET-only and the PET/MR systems were analyzed using a 2-way Analysis of Variance (ANOVA). Comparison of DIXON-based AC (PET/MR) with emission data derived from the PET-only system revealed average inter-system differences of −33 ± 14% (p < 0.05) for the K1 parameter and −19 ± 9% (p < 0.05) for k2. Using a CT-based AC for PET/MR resulted in slightly lower systematic differences of −16 ± 18% for K1 and −9 ± 10% for k2. The average differences in VT were −18 ± 10% (p < 0.05) for DIXON- and −8 ± 13% for CT-based AC. Significant systematic differences were observed for kinetic parameters derived from emission data obtained from PET/MR and PET-only imaging due to different standard AC methods employed. Therefore, a transfer of imaging protocols from PET-only to PET/MR systems is not straightforward without application of proper correction methods. Clinical Trial Registration: www.clinicaltrialsregister.eu, identifier 2013-001724-19 PMID:28769742

Human-animal bonds II: the role of pets in family systems and family therapy.

PubMed

Walsh, Froma

2009-12-01

The vast majority of pet owners regard their companion animals as family members, yet the role of pets in family systems and family therapy has received little attention in research, training, and practice. This article first notes the benefits of family pets and their importance for resilience. It then examines their role in couple and family processes and their involvement in relational dynamics and tensions. Next, it addresses bereavement in the loss of a cherished pet, influences complicating grief, and facilitation of mourning and adaptation. Finally, it explores the ways that clients' pets and the use of therapists' companion animals in animal-assisted therapy can inform and enrich couple and family therapy as valuable resources in healing.

MRI-Based Nonrigid Motion Correction in Simultaneous PET/MRI

PubMed Central

Chun, Se Young; Reese, Timothy G.; Ouyang, Jinsong; Guerin, Bastien; Catana, Ciprian; Zhu, Xuping; Alpert, Nathaniel M.; El Fakhri, Georges

2014-01-01

Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise. This paper presents an approach to respiratory motion correction using simultaneous PET/MRI to demonstrate initial results in phantoms, rabbits, and nonhuman primates and discusses the prospects for clinical application. Methods Studies with a deformable phantom, a free-breathing primate, and rabbits implanted with radioactive beads were performed with simultaneous PET/MRI. Motion fields were estimated from concurrently acquired tagged MR images using 2 B-spline nonrigid image registration methods and incorporated into a PET list-mode ordered-subsets expectation maximization algorithm. Using the measured motion fields to transform both the emission data and the attenuation data, we could use all the coincidence data to reconstruct any phase of the respiratory cycle. We compared the resulting SNR and the channelized Hotelling observer (CHO) detection signal-to-noise ratio (SNR) in the motion-corrected reconstruction with the results obtained from standard gating and uncorrected studies. Results Motion correction virtually eliminated motion blur without reducing SNR, yielding images with SNR comparable to those obtained by gating with 5–8 times longer acquisitions in all studies. The CHO study in dynamic phantoms demonstrated a significant improvement (166%–276%) in lesion detection SNR with MRI-based motion correction as compared with gating (P < 0.001). This improvement was 43%–92% for large motion compared with lesion detection without motion correction (P < 0.001). CHO SNR in the rabbit studies confirmed these results. Conclusion Tagged MRI motion correction in simultaneous PET/MRI significantly improves lesion detection compared with respiratory gating and no motion correction while reducing radiation dose. In vivo primate and rabbit studies confirmed the improvement in PET image quality and provide the rationale for evaluation in simultaneous whole-body PET/MRI clinical studies. PMID:22743250

Generalized whole-body Patlak parametric imaging for enhanced quantification in clinical PET.

PubMed

Karakatsanis, Nicolas A; Zhou, Yun; Lodge, Martin A; Casey, Michael E; Wahl, Richard L; Zaidi, Habib; Rahmim, Arman

2015-11-21

We recently developed a dynamic multi-bed PET data acquisition framework to translate the quantitative benefits of Patlak voxel-wise analysis to the domain of routine clinical whole-body (WB) imaging. The standard Patlak (sPatlak) linear graphical analysis assumes irreversible PET tracer uptake, ignoring the effect of FDG dephosphorylation, which has been suggested by a number of PET studies. In this work: (i) a non-linear generalized Patlak (gPatlak) model is utilized, including a net efflux rate constant kloss, and (ii) a hybrid (s/g)Patlak (hPatlak) imaging technique is introduced to enhance contrast to noise ratios (CNRs) of uptake rate Ki images. Representative set of kinetic parameter values and the XCAT phantom were employed to generate realistic 4D simulation PET data, and the proposed methods were additionally evaluated on 11 WB dynamic PET patient studies. Quantitative analysis on the simulated Ki images over 2 groups of regions-of-interest (ROIs), with low (ROI A) or high (ROI B) true kloss relative to Ki, suggested superior accuracy for gPatlak. Bias of sPatlak was found to be 16-18% and 20-40% poorer than gPatlak for ROIs A and B, respectively. By contrast, gPatlak exhibited, on average, 10% higher noise than sPatlak. Meanwhile, the bias and noise levels for hPatlak always ranged between the other two methods. In general, hPatlak was seen to outperform all methods in terms of target-to-background ratio (TBR) and CNR for all ROIs. Validation on patient datasets demonstrated clinical feasibility for all Patlak methods, while TBR and CNR evaluations confirmed our simulation findings, and suggested presence of non-negligible kloss reversibility in clinical data. As such, we recommend gPatlak for highly quantitative imaging tasks, while, for tasks emphasizing lesion detectability (e.g. TBR, CNR) over quantification, or for high levels of noise, hPatlak is instead preferred. Finally, gPatlak and hPatlak CNR was systematically higher compared to routine SUV values.

Generalized whole-body Patlak parametric imaging for enhanced quantification in clinical PET

NASA Astrophysics Data System (ADS)

Karakatsanis, Nicolas A.; Zhou, Yun; Lodge, Martin A.; Casey, Michael E.; Wahl, Richard L.; Zaidi, Habib; Rahmim, Arman

2015-11-01

We recently developed a dynamic multi-bed PET data acquisition framework to translate the quantitative benefits of Patlak voxel-wise analysis to the domain of routine clinical whole-body (WB) imaging. The standard Patlak (sPatlak) linear graphical analysis assumes irreversible PET tracer uptake, ignoring the effect of FDG dephosphorylation, which has been suggested by a number of PET studies. In this work: (i) a non-linear generalized Patlak (gPatlak) model is utilized, including a net efflux rate constant kloss, and (ii) a hybrid (s/g)Patlak (hPatlak) imaging technique is introduced to enhance contrast to noise ratios (CNRs) of uptake rate Ki images. Representative set of kinetic parameter values and the XCAT phantom were employed to generate realistic 4D simulation PET data, and the proposed methods were additionally evaluated on 11 WB dynamic PET patient studies. Quantitative analysis on the simulated Ki images over 2 groups of regions-of-interest (ROIs), with low (ROI A) or high (ROI B) true kloss relative to Ki, suggested superior accuracy for gPatlak. Bias of sPatlak was found to be 16-18% and 20-40% poorer than gPatlak for ROIs A and B, respectively. By contrast, gPatlak exhibited, on average, 10% higher noise than sPatlak. Meanwhile, the bias and noise levels for hPatlak always ranged between the other two methods. In general, hPatlak was seen to outperform all methods in terms of target-to-background ratio (TBR) and CNR for all ROIs. Validation on patient datasets demonstrated clinical feasibility for all Patlak methods, while TBR and CNR evaluations confirmed our simulation findings, and suggested presence of non-negligible kloss reversibility in clinical data. As such, we recommend gPatlak for highly quantitative imaging tasks, while, for tasks emphasizing lesion detectability (e.g. TBR, CNR) over quantification, or for high levels of noise, hPatlak is instead preferred. Finally, gPatlak and hPatlak CNR was systematically higher compared to routine SUV values.

Policies on pets for healthy cities: a conceptual framework

PubMed Central

Rock, Melanie J.; Adams, Cindy L.; Degeling, Chris; Massolo, Alessandro; McCormack, Gavin R.

2015-01-01

Drawing on the One Health concept, and integrating a dual focus on public policy and practices of caring from the Ottawa Charter for Health Promotion, we outline a conceptual framework to help guide the development and assessment of local governments' policies on pets. This framework emphasizes well-being in human populations, while recognizing that these outcomes relate to the well-being of non-human animals. Five intersecting spheres of activity, each associated with local governments' jurisdiction over pets, are presented: (i) preventing threats and nuisances from pets, (ii) meeting pets' emotional and physical needs, (iii) procuring pets ethically, (iv) providing pets with veterinary services and (v) licensing and identifying pets. This conceptual framework acknowledges the tenets of previous health promotion frameworks, including overlapping and intersecting influences. At the same time, this framework proposes to advance our understanding of health promotion and, more broadly, population health by underscoring interdependence between people and pets as well as the dynamism of urbanized ecologies. PMID:24694682

MRI-guided brain PET image filtering and partial volume correction

NASA Astrophysics Data System (ADS)

Yan, Jianhua; Chu-Shern Lim, Jason; Townsend, David W.

2015-02-01

Positron emission tomography (PET) image quantification is a challenging problem due to limited spatial resolution of acquired data and the resulting partial volume effects (PVE), which depend on the size of the structure studied in relation to the spatial resolution and which may lead to over or underestimation of the true tissue tracer concentration. In addition, it is usually necessary to perform image smoothing either during image reconstruction or afterwards to achieve a reasonable signal-to-noise ratio. Typically, an isotropic Gaussian filtering (GF) is used for this purpose. However, the noise suppression is at the cost of deteriorating spatial resolution. As hybrid imaging devices such as PET/MRI have become available, the complementary information derived from high definition morphologic images could be used to improve the quality of PET images. In this study, first of all, we propose an MRI-guided PET filtering method by adapting a recently proposed local linear model and then incorporate PVE into the model to get a new partial volume correction (PVC) method without parcellation of MRI. In addition, both the new filtering and PVC are voxel-wise non-iterative methods. The performance of the proposed methods were investigated with simulated dynamic FDG brain dataset and 18F-FDG brain data of a cervical cancer patient acquired with a simultaneous hybrid PET/MR scanner. The initial simulation results demonstrated that MRI-guided PET image filtering can produce less noisy images than traditional GF and bias and coefficient of variation can be further reduced by MRI-guided PET PVC. Moreover, structures can be much better delineated in MRI-guided PET PVC for real brain data.

Recent advances in parametric neuroreceptor mapping with dynamic PET: basic concepts and graphical analyses.

PubMed

Seo, Seongho; Kim, Su Jin; Lee, Dong Soo; Lee, Jae Sung

2014-10-01

Tracer kinetic modeling in dynamic positron emission tomography (PET) has been widely used to investigate the characteristic distribution patterns or dysfunctions of neuroreceptors in brain diseases. Its practical goal has progressed from regional data quantification to parametric mapping that produces images of kinetic-model parameters by fully exploiting the spatiotemporal information in dynamic PET data. Graphical analysis (GA) is a major parametric mapping technique that is independent on any compartmental model configuration, robust to noise, and computationally efficient. In this paper, we provide an overview of recent advances in the parametric mapping of neuroreceptor binding based on GA methods. The associated basic concepts in tracer kinetic modeling are presented, including commonly-used compartment models and major parameters of interest. Technical details of GA approaches for reversible and irreversible radioligands are described, considering both plasma input and reference tissue input models. Their statistical properties are discussed in view of parametric imaging.

Myocardial perfusion quantification using simultaneously acquired 13 NH3 -ammonia PET and dynamic contrast-enhanced MRI in patients at rest and stress.

PubMed

Kunze, Karl P; Nekolla, Stephan G; Rischpler, Christoph; Zhang, Shelley HuaLei; Hayes, Carmel; Langwieser, Nicolas; Ibrahim, Tareq; Laugwitz, Karl-Ludwig; Schwaiger, Markus

2018-04-19

Systematic differences with respect to myocardial perfusion quantification exist between DCE-MRI and PET. Using the potential of integrated PET/MRI, this study was conceived to compare perfusion quantification on the basis of simultaneously acquired 13 NH 3 -ammonia PET and DCE-MRI data in patients at rest and stress. Twenty-nine patients were examined on a 3T PET/MRI scanner. DCE-MRI was implemented in dual-sequence design and additional T 1 mapping for signal normalization. Four different deconvolution methods including a modified version of the Fermi technique were compared against 13 NH 3 -ammonia results. Cohort-average flow comparison yielded higher resting flows for DCE-MRI than for PET and, therefore, significantly lower DCE-MRI perfusion ratios under the common assumption of equal arterial and tissue hematocrit. Absolute flow values were strongly correlated in both slice-average (R 2  = 0.82) and regional (R 2  = 0.7) evaluations. Different DCE-MRI deconvolution methods yielded similar flow result with exception of an unconstrained Fermi method exhibiting outliers at high flows when compared with PET. Thresholds for Ischemia classification may not be directly tradable between PET and MRI flow values. Differences in perfusion ratios between PET and DCE-MRI may be lifted by using stress/rest-specific hematocrit conversion. Proper physiological constraints are advised in model-constrained deconvolution. © 2018 International Society for Magnetic Resonance in Medicine.

18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging.

PubMed

Nishii, Ryuichi; Higashi, Tatsuya; Kagawa, Shinya; Okuyama, Chio; Kishibe, Yoshihiko; Takahashi, Masaaki; Okina, Tomoko; Suzuki, Norio; Hasegawa, Hiroshi; Nagahama, Yasuhiro; Ishizu, Koichi; Oishi, Naoya; Kimura, Hiroyuki; Watanabe, Hiroyuki; Ono, Masahiro; Saji, Hideo; Yamauchi, Hiroshi

2018-05-01

Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2- 18 F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine ( 18 F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that 18 F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, https://doi.org/10.1007/s12149-018-1236-1 , 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18 F-FPYBF-2 in normal healthy volunteers as a first-in-man study. Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range 25-56) were included and underwent 18 F-FPYBF-2 PET/CT study for the evaluation of radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body (chest and abdomen) was performed at 0-10 min and a 15-min whole-body static scan was performed six times after the injection of 18 F-FPYBF-2. After reconstructing PET and CT image data, individual organ time-activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans. The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses. Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18 F-FPYBF-2. High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48 ± 1.25 µSv/MBq. The higher absorbed doses were estimated for the liver (28.98 ± 12.49 and 36.21 ± 15.64 µGy/MBq), the brain (20.93 ± 4.56 and 23.05 ± 5.03µ Gy/MBq), the osteogenic cells (9.67 ± 1.67 and 10.29 ± 1.70 µGy/MBq), the small intestines (9.12 ± 2.61 and 11.12 ± 3.15 µGy/MBq), and the kidneys (7.81 ± 2.62 and 8.71 ± 2.90 µGy/MBq) for male and female, respectively. The ED for the adult dosimetric model was similar to those of other agents used for amyloid PET imaging. The diagnostic dosage of 185-370 MBq of 18 F-FPYBF-2 was considered to be acceptable for administration in patients as a diagnostic tool for the evaluation of AD.

Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

PubMed

Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

2013-01-01

This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P < 0.04). In metastatic disease, multivariate analysis found VB, K(1), and k(3) to be significant variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic factors for OS in the entire group of patients that were significant at multivariate analysis were stage of disease, VB, K(1), and (18)F-FDG INF (P < 0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients with a high (18)F-FDG INF, low VB, and high K(1) was 3 mo, as opposed to 14 mo in patients with a low (18)F-FDG INF, high VB, and low K(1) (P < 0.021), irrespective of stage and resectability. Quantitative (18)F-FDG kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) Combined with Positron Emission Tomography-Computed Tomography (PET-CT) and Video-Electroencephalography (VEEG) Have Excellent Diagnostic Value in Preoperative Localization of Epileptic Foci in Children with Epilepsy.

PubMed

Wang, Gui-Bin; Long, Wei; Li, Xiao-Dong; Xu, Guang-Yin; Lu, Ji-Xiang

2017-01-01

BACKGROUND To investigate the effect that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has on surgical decision making relative to video-electroencephalography (VEEG) and positron emission tomography-computed tomography (PET-CT), and if the differences in these variables translates to differences in surgical outcomes. MATERIAL AND METHODS A total of 166 children with epilepsy undergoing preoperative DCE-MRI, VEEG, and PET-CT examinations, surgical resection of epileptic foci, and intraoperative electrocorticography (ECoG) monitoring were enrolled. All children were followed up for 12 months and grouped by Engles prognostic classification for epilepsy. Based on intraoperative ECoG as gold standard, the diagnostic values of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and combined application of DCE-MRI, VEEG, and PET-CT in preoperative localization for epileptic foci were evaluated. RESULTS The sensitivity of DCE-MRI, VEEG, and PET-CT was 59.64%, 76.51%, and 93.98%, respectively; the accuracy of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, and DCE-MRI combined with PET-CT was 57.58%, 67.72%, 91.03%, 91.23%, and 96.49%, respectively. Localization accuracy rate of the combination of DCE-MRI, VEEG, and PET-CT was 98.25% (56/57), which was higher than that of DCE-MRI combined with VEEG and of DCE-MRI combined with PET-CT. No statistical difference was found in the accuracy rate of localization between these three combined techniques. During the 12-month follow-up, children were grouped into Engles grade I (n=106), II (n=31), III (n=21), and IV (n=8) according to postoperative conditions. CONCLUSIONS All DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and DCE-MRI combined with VEEG and PET-CT examinations have excellent accuracy in preoperative localization of epileptic foci and present excellent postoperative efficiency, suggesting that these combined imaging methods are suitable for serving as the reference basis in preoperative localization of epileptic foci in children with epilepsy.

Whole-body direct 4D parametric PET imaging employing nested generalized Patlak expectation-maximization reconstruction

PubMed Central

Karakatsanis, Nicolas A.; Casey, Michael E.; Lodge, Martin A.; Rahmim, Arman; Zaidi, Habib

2016-01-01

Whole-body (WB) dynamic PET has recently demonstrated its potential in translating the quantitative benefits of parametric imaging to the clinic. Post-reconstruction standard Patlak (sPatlak) WB graphical analysis utilizes multi-bed multi-pass PET acquisition to produce quantitative WB images of the tracer influx rate Ki as a complimentary metric to the semi-quantitative standardized uptake value (SUV). The resulting Ki images may suffer from high noise due to the need for short acquisition frames. Meanwhile, a generalized Patlak (gPatlak) WB post-reconstruction method had been suggested to limit Ki bias of sPatlak analysis at regions with non-negligible 18F-FDG uptake reversibility; however, gPatlak analysis is non-linear and thus can further amplify noise. In the present study, we implemented, within the open-source Software for Tomographic Image Reconstruction (STIR) platform, a clinically adoptable 4D WB reconstruction framework enabling efficient estimation of sPatlak and gPatlak images directly from dynamic multi-bed PET raw data with substantial noise reduction. Furthermore, we employed the optimization transfer methodology to accelerate 4D expectation-maximization (EM) convergence by nesting the fast image-based estimation of Patlak parameters within each iteration cycle of the slower projection-based estimation of dynamic PET images. The novel gPatlak 4D method was initialized from an optimized set of sPatlak ML-EM iterations to facilitate EM convergence. Initially, realistic simulations were conducted utilizing published 18F-FDG kinetic parameters coupled with the XCAT phantom. Quantitative analyses illustrated enhanced Ki target-to-background ratio (TBR) and especially contrast-to-noise ratio (CNR) performance for the 4D vs. the indirect methods and static SUV. Furthermore, considerable convergence acceleration was observed for the nested algorithms involving 10–20 sub-iterations. Moreover, systematic reduction in Ki % bias and improved TBR were observed for gPatlak vs. sPatlak. Finally, validation on clinical WB dynamic data demonstrated the clinical feasibility and superior Ki CNR performance for the proposed 4D framework compared to indirect Patlak and SUV imaging. PMID:27383991

Whole-body direct 4D parametric PET imaging employing nested generalized Patlak expectation-maximization reconstruction

NASA Astrophysics Data System (ADS)

Karakatsanis, Nicolas A.; Casey, Michael E.; Lodge, Martin A.; Rahmim, Arman; Zaidi, Habib

2016-08-01

Whole-body (WB) dynamic PET has recently demonstrated its potential in translating the quantitative benefits of parametric imaging to the clinic. Post-reconstruction standard Patlak (sPatlak) WB graphical analysis utilizes multi-bed multi-pass PET acquisition to produce quantitative WB images of the tracer influx rate K i as a complimentary metric to the semi-quantitative standardized uptake value (SUV). The resulting K i images may suffer from high noise due to the need for short acquisition frames. Meanwhile, a generalized Patlak (gPatlak) WB post-reconstruction method had been suggested to limit K i bias of sPatlak analysis at regions with non-negligible 18F-FDG uptake reversibility; however, gPatlak analysis is non-linear and thus can further amplify noise. In the present study, we implemented, within the open-source software for tomographic image reconstruction platform, a clinically adoptable 4D WB reconstruction framework enabling efficient estimation of sPatlak and gPatlak images directly from dynamic multi-bed PET raw data with substantial noise reduction. Furthermore, we employed the optimization transfer methodology to accelerate 4D expectation-maximization (EM) convergence by nesting the fast image-based estimation of Patlak parameters within each iteration cycle of the slower projection-based estimation of dynamic PET images. The novel gPatlak 4D method was initialized from an optimized set of sPatlak ML-EM iterations to facilitate EM convergence. Initially, realistic simulations were conducted utilizing published 18F-FDG kinetic parameters coupled with the XCAT phantom. Quantitative analyses illustrated enhanced K i target-to-background ratio (TBR) and especially contrast-to-noise ratio (CNR) performance for the 4D versus the indirect methods and static SUV. Furthermore, considerable convergence acceleration was observed for the nested algorithms involving 10-20 sub-iterations. Moreover, systematic reduction in K i % bias and improved TBR were observed for gPatlak versus sPatlak. Finally, validation on clinical WB dynamic data demonstrated the clinical feasibility and superior K i CNR performance for the proposed 4D framework compared to indirect Patlak and SUV imaging.

Improved estimation of parametric images of cerebral glucose metabolic rate from dynamic FDG-PET using volume-wise principle component analysis

NASA Astrophysics Data System (ADS)

Dai, Xiaoqian; Tian, Jie; Chen, Zhe

2010-03-01

Parametric images can represent both spatial distribution and quantification of the biological and physiological parameters of tracer kinetics. The linear least square (LLS) method is a well-estimated linear regression method for generating parametric images by fitting compartment models with good computational efficiency. However, bias exists in LLS-based parameter estimates, owing to the noise present in tissue time activity curves (TTACs) that propagates as correlated error in the LLS linearized equations. To address this problem, a volume-wise principal component analysis (PCA) based method is proposed. In this method, firstly dynamic PET data are properly pre-transformed to standardize noise variance as PCA is a data driven technique and can not itself separate signals from noise. Secondly, the volume-wise PCA is applied on PET data. The signals can be mostly represented by the first few principle components (PC) and the noise is left in the subsequent PCs. Then the noise-reduced data are obtained using the first few PCs by applying 'inverse PCA'. It should also be transformed back according to the pre-transformation method used in the first step to maintain the scale of the original data set. Finally, the obtained new data set is used to generate parametric images using the linear least squares (LLS) estimation method. Compared with other noise-removal method, the proposed method can achieve high statistical reliability in the generated parametric images. The effectiveness of the method is demonstrated both with computer simulation and with clinical dynamic FDG PET study.

Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

PubMed

Mathieu, Cédric; Ferrer, Ludovic; Carlier, Thomas; Colombié, Mathilde; Rusu, Daniela; Kraeber-Bodéré, Françoise; Campion, Loic; Rousseau, Caroline

2015-01-01

Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.

Kinetic modeling in PET imaging of hypoxia

PubMed Central

Li, Fan; Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

2014-01-01

Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia. PMID:25250200

Dynamic Changes in Striatal mGluR1 But Not mGluR5 during Pathological Progression of Parkinson's Disease in Human Alpha-Synuclein A53T Transgenic Rats: A Multi-PET Imaging Study.

PubMed

Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Furutsuka, Kenji; Nengaki, Nobuki; Shimoda, Yoko; Shiomi, Satoshi; Takei, Makoto; Hashimoto, Hiroki; Yui, Joji; Wakizaka, Hidekatsu; Hatori, Akiko; Xie, Lin; Kumata, Katsushi; Zhang, Ming-Rong

2016-01-13

Parkinson's disease (PD) is a prevalent degenerative disorder affecting the CNS that is primarily characterized by resting tremor and movement deficits. Group I metabotropic glutamate receptor subtypes 1 and 5 (mGluR1 and mGluR5, respectively) are important targets for investigation in several CNS disorders. In the present study, we investigated the in vivo roles of mGluR1 and mGluR5 in chronic PD pathology by performing longitudinal positron emission tomography (PET) imaging in A53T transgenic (A53T-Tg) rats expressing an abnormal human α-synuclein (ASN) gene. A53T-Tg rats showed a dramatic decline in general motor activities with age, along with abnormal ASN aggregation and striatal neuron degeneration. In longitudinal PET imaging, striatal nondisplaceable binding potential (BPND) values for [(11)C]ITDM (N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]methylbenzamide), a selective PET ligand for mGluR1, temporarily increased before PD symptom onset and dramatically decreased afterward with age. However, striatal BPND values for (E)-[(11)C]ABP688 [3-(6-methylpyridin-2-ylethynyl)-cyclohex-2-enone-(E)-O-[(11)C]methyloxime], a specific PET ligand for mGluR5, remained constant during experimental terms. The dynamic changes in striatal mGluR1 BPND values also showed a high correlation in pathological decreases in general motor activities. Furthermore, declines in mGluR1 BPND values were correlated with decreases in BPND values for [(18)F]FE-PE2I [(E)-N-(3-iodoprop-2E-enyl)-2β-carbo-[(18)F]fluoroethoxy-3β-(4-methylphenyl) nortropane], a specific PET ligand for the dopamine transporter, a biomarker for dopaminergic neurons. In conclusion, our results have demonstrated for the first time that dynamic changes occur in mGluR1, but not mGluR5, that accompany pathological progression in a PD animal model. Synaptic signaling by glutamate, the principal excitatory neurotransmitter in the brain, is modulated by group I metabotropic glutamate receptors, including the mGluR1 and mGluR5 subtypes. In the brain, mGluR1 and mGluR5 have distinct functional roles and regional distributions. Their roles in brain pathology, however, are not well characterized. Using longitudinal PET imaging in a chronic rat model of PD, we demonstrated that expression of mGluR1, but not mGluR5, dynamically changed in the striatum accompanying pathological PD progression. These findings imply that monitoring mGluR1 in vivo may provide beneficial information to further understand central nervous system disorders. Copyright © 2016 the authors 0270-6474/16/360376-10$15.00/0.

Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences

PubMed Central

Fakhri, Georges El; Trott, Cathryn M.; Sitek, Arkadiusz; Bonab, Ali; Alpert, Nathaniel M.

2013-01-01

Purpose With single-photon emission computed tomography, simultaneous imaging of two physiological processes relies on discrimination of the energy of the emitted gamma rays, whereas the application of dual-tracer imaging to positron emission tomography (PET) imaging has been limited by the characteristic 511-keV emissions. Procedures To address this limitation, we developed a novel approach based on generalized factor analysis of dynamic sequences (GFADS) that exploits spatio-temporal differences between radiotracers and applied it to near-simultaneous imaging of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) (brain metabolism) and 11C-raclopride (D2) with simulated human data and experimental rhesus monkey data. We show theoretically and verify by simulation and measurement that GFADS can separate FDG and raclopride measurements that are made nearly simultaneously. Results The theoretical development shows that GFADS can decompose the studies at several levels: (1) It decomposes the FDG and raclopride study so that they can be analyzed as though they were obtained separately. (2) If additional physiologic/anatomic constraints can be imposed, further decomposition is possible. (3) For the example of raclopride, specific and nonspecific binding can be determined on a pixel-by-pixel basis. We found good agreement between the estimated GFADS factors and the simulated ground truth time activity curves (TACs), and between the GFADS factor images and the corresponding ground truth activity distributions with errors less than 7.3±1.3 %. Biases in estimation of specific D2 binding and relative metabolism activity were within 5.9±3.6 % compared to the ground truth values. We also evaluated our approach in simultaneous dual-isotope brain PET studies in a rhesus monkey and obtained accuracy of better than 6 % in a mid-striatal volume, for striatal activity estimation. Conclusions Dynamic image sequences acquired following near-simultaneous injection of two PET radiopharmaceuticals can be separated into components based on the differences in the kinetics, provided their kinetic behaviors are distinct. PMID:23636489

Quantification of Dynamic [18F]FDG Pet Studies in Acute Lung Injury.

PubMed

Grecchi, Elisabetta; Veronese, Mattia; Moresco, Rosa Maria; Bellani, Giacomo; Pesenti, Antonio; Messa, Cristina; Bertoldo, Alessandra

2016-02-01

This work aims to investigate lung glucose metabolism using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging in acute lung injury (ALI) patients. Eleven ALI patients and five healthy controls underwent a dynamic [(18)F]FDG PET/X-ray computed tomography (CT) scan. The standardized uptake values (SUV) and three different methods for the quantification of glucose metabolism (i.e., ratio, Patlak, and spectral analysis iterative filter, SAIF) were applied both at the region and the voxel levels. SUV reported a lower correlation than the ratio with the net tracer uptake. Patlak and SAIF analyses did not show any significant spatial or quantitative (R(2) > 0.80) difference. The additional information provided by SAIF showed that in lung inflammation, elevated tracer uptake is coupled with abnormal tracer exchanges within and between lung tissue compartments. Full kinetic modeling provides a multi-parametric description of glucose metabolism in the lungs. This allows characterizing the spatial distribution of lung inflammation as well as returning the functional state of the tissues.

Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI.

PubMed

Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

2016-04-01

This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization.

Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI

PubMed Central

Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Rosen, Bruce R; Mandeville, Joseph B

2016-01-01

This study investigated the dynamics of dopamine receptor desensitization and internalization, thereby proposing a new technique for non-invasive, in vivo measurements of receptor adaptations. The D2/D3 agonist quinpirole, which induces receptor internalization in vitro, was administered at graded doses in non-human primates while imaging with simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). A pronounced temporal divergence between receptor occupancy and fMRI signal was observed: occupancy remained elevated while fMRI responded transiently. Analogous experiments with an antagonist (prochlorperazine) and a lower-affinity agonist (ropinirole) exhibited reduced temporal dissociation between occupancy and function, consistent with a mechanism of desensitization and internalization that depends upon drug efficacy and affinity. We postulated a model that incorporates internalization into a neurovascular-coupling relationship. This model yielded in vivo desensitization/internalization rates (0.2/min for quinpirole) consistent with published in vitro measurements. Overall, these results suggest that simultaneous PET/fMRI enables characterization of dynamic neuroreceptor adaptations in vivo, and may offer a first non-invasive method for assessing receptor desensitization and internalization. PMID:26388148

Imaging tumor perfusion and oxidative metabolism in patients with head-and-neck cancer using 1- [11C]-acetate PET during radiotherapy: preliminary results.

PubMed

Sun, Aijun; Johansson, Silvia; Turesson, Ingela; Daşu, Alexandru; Sörensen, Jens

2012-02-01

A growing body of in vitro evidence links alterations of the intermediary metabolism in cancer to treatment outcome. This study aimed to characterize tumor oxidative metabolism and perfusion in vivo using dynamic positron emission tomography (PET) with 1- [(11)C]-acetate (ACE) during radiotherapy. Nine patients with head-and-neck cancer were studied. Oxidative metabolic rate (k(mono)) and perfusion (rF) of the primary tumors were assessed by dynamic ACE-PET at baseline and after 15, 30, and 55 Gy was delivered. Tumor glucose uptake (Tglu) was evaluated with [(18)F]-fluorodeoxyglucose PET at baseline. Patients were grouped into complete (CR, n = 6) and partial responders (PR, n = 3) to radiotherapy. The 3 PR patients died within a median follow-up period of 33 months. Baseline k(mono) was almost twice as high in CR as in PR (p = 0.02) and Tglu was lower in CR than in PR (p = 0.04). k(mono) increased during radiotherapy in PR (p = 0.004) but remained unchanged in CR. There were no differences in rF between CR and PR at any dosage. k(mono) and rF were coupled in CR (p = 0.001), but not in PR. This study shows that radiosensitive tumors might rely predominantly on oxidative metabolism for their bioenergetic needs. The impairment of oxidative metabolism in radioresistant tumors is potentially reversible, suggesting that therapies targeting the intermediary metabolism might improve treatment outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

Water availability predicts forest canopy height at the global scale.

PubMed

Klein, Tamir; Randin, Christophe; Körner, Christian

2015-12-01

The tendency of trees to grow taller with increasing water availability is common knowledge. Yet a robust, universal relationship between the spatial distribution of water availability and forest canopy height (H) is lacking. Here, we created a global water availability map by calculating an annual budget as the difference between precipitation (P) and potential evapotranspiration (PET) at a 1-km spatial resolution, and in turn correlated it with a global H map of the same resolution. Across forested areas over the globe, Hmean increased with P-PET, roughly: Hmean (m) = 19.3 + 0.077*(P-PET). Maximum forest canopy height also increased gradually from ~ 5 to ~ 50 m, saturating at ~ 45 m for P-PET > 500 mm. Forests were far from their maximum height potential in cold, boreal regions and in disturbed areas. The strong association between forest height and P-PET provides a useful tool when studying future forest dynamics under climate change, and in quantifying anthropogenic forest disturbance. © 2015 John Wiley & Sons Ltd/CNRS.

Photoinduced electron transfer in a room temperature ionic liquid 1-butyl-3-methylimidazolium octyl sulfate micelle: a temperature dependent study.

PubMed

Sarkar, Souravi; Mandal, Sarthak; Pramanik, Rajib; Ghatak, Chiranjib; Rao, Vishal Govind; Sarkar, Nilmoni

2011-05-19

The effect of temperature on the dynamics of photoinduced electron transfer (PET) between different coumarin dyes and N,N-dimethyl aniline in a room temperature ionic liquid 1-butyl-3-methylimidazolium octyl sulfate ([C(4)mim][C(8)SO(4)]) micelle have been investigated using steady-state and time-resolved fluorescence quenching measurements at four different temperatures: 208, 298, 308, and 318 K. The quenching rates (k(q)(TR)) of the PET process in this micellar system are found to be lower than the PET rate in sodium dodecyl sulfate and Triton-X 100 micelle and almost comparable to the dodecyl trimethyl ammonium bromide and cetyl trimethyl ammonium bromide micelle due to larger donor–acceptor separation in the micellar phase. The temperature dependent PET rates are well correlated with the Arrhenius type of correlation for all the coumarin dyes. Marcus type of inversion in PET rates has been observed at relatively lower exergonicity, and the correlation plots gradually move upward with the increase of temperature. © 2011 American Chemical Society

Spatiotemporal PET Imaging of Dynamic Metabolic Changes After Therapeutic Approaches of Induced Pluripotent Stem Cells, Neuronal Stem Cells, and a Chinese Patent Medicine in Stroke.

PubMed

Zhang, Hong; Song, Fahuan; Xu, Caiyun; Liu, Hao; Wang, Zefeng; Li, Jinhui; Wu, Shuang; YehuaShen; Chen, Yao; Zhu, Yunqi; Du, Ruili; Tian, Mei

2015-11-01

This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia-reperfusion injury. Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P < 0.05) or glucose transporter-1 expression (P < 0.01). Immunohistochemical and immunofluorescence studies found that transplanted iPSCs survived and migrated to the ischemic region and expressed protein markers for cells of interest. Spatiotemporal PET imaging with (18)F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia-reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A quantum dynamical study of the rotation of the dihydrogen ligand in the Fe(H)2(H2)(PEtPh2)3 coordination complex.

PubMed

Gonzalez, Megan E; Eckert, Juergen; Aquino, Adelia J A; Poirier, Bill

2018-04-21

Progress in the hydrogen fuel field requires a clear understanding and characterization of how materials of interest interact with hydrogen. Due to the inherently quantum mechanical nature of hydrogen nuclei, any theoretical studies of these systems must be treated quantum dynamically. One class of material that has been examined in this context are dihydrogen complexes. Since their discovery by Kubas in 1984, many such complexes have been studied both experimentally and theoretically. This particular study examines the rotational dynamics of the dihydrogen ligand in the Fe(H) 2 (H 2 )(PEtPh 2 ) 3 complex, allowing for full motion in both the rotational degrees of freedom and treating the quantum dynamics (QD) explicitly. A "gas-phase" global potential energy surface is first constructed using density functional theory with the Becke, 3-parameter, Lee-Yang-Parr functional; this is followed by an exact QD calculation of the corresponding rotation/libration states. The results provide insight into the dynamical correlation of the two rotation angles as well as a comprehensive analysis of both ground- and excited-state librational tunneling splittings. The latter was computed to be 6.914 cm -1 -in excellent agreement with the experimental value of 6.4 cm -1 . This work represents the first full-dimensional ab initio exact QD calculation ever performed for dihydrogen ligand rotation in a coordination complex.

A quantum dynamical study of the rotation of the dihydrogen ligand in the Fe(H)2(H2)(PEtPh2)3 coordination complex

NASA Astrophysics Data System (ADS)

Gonzalez, Megan E.; Eckert, Juergen; Aquino, Adelia J. A.; Poirier, Bill

2018-04-01

Progress in the hydrogen fuel field requires a clear understanding and characterization of how materials of interest interact with hydrogen. Due to the inherently quantum mechanical nature of hydrogen nuclei, any theoretical studies of these systems must be treated quantum dynamically. One class of material that has been examined in this context are dihydrogen complexes. Since their discovery by Kubas in 1984, many such complexes have been studied both experimentally and theoretically. This particular study examines the rotational dynamics of the dihydrogen ligand in the Fe(H)2(H2)(PEtPh2)3 complex, allowing for full motion in both the rotational degrees of freedom and treating the quantum dynamics (QD) explicitly. A "gas-phase" global potential energy surface is first constructed using density functional theory with the Becke, 3-parameter, Lee-Yang-Parr functional; this is followed by an exact QD calculation of the corresponding rotation/libration states. The results provide insight into the dynamical correlation of the two rotation angles as well as a comprehensive analysis of both ground- and excited-state librational tunneling splittings. The latter was computed to be 6.914 cm-1—in excellent agreement with the experimental value of 6.4 cm-1. This work represents the first full-dimensional ab initio exact QD calculation ever performed for dihydrogen ligand rotation in a coordination complex.

Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

DTIC Science & Technology

2015-09-01

and PET images. Figure 2 highlights the dynamic uptake of TSPO as compared to muscle. Across 60 minutes the %ID/cc continues to increase which is...p53 double null mutant mouse model. Towards that end, we have successfully acquired anatomic MRI and PET data in orthotopic tumors within the Pten...castration resistant prostate cancer, MRI, PET , FDHT, image optimization 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES

Effects of flow changes on radiotracer binding: Simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation.

PubMed

Sander, Christin Y; Mandeville, Joseph B; Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Rosen, Bruce R

2017-01-01

The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO 2 ) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D 2 /D 3 receptor binding of [ 11 C]raclopride or [ 18 F]fallypride was monitored with dynamic PET. Experiments showed that neither time activity curves nor quantification of binding through binding potentials ( BP ND ) were measurably affected by CBF increases, which were larger than two-fold. Simulations of experimental procedures showed that even large changes in CBF should have little effect on the time activity curves of radiotracers, given a set of realistic assumptions. The proposed method can be applied to experimentally assess the flow sensitivity of other radiotracers. Results demonstrate that CBF changes, which often occur due to behavioral tasks or pharmacological challenges, do not affect PET [ 11 C]raclopride or [ 18 F]fallypride binding studies and their quantification. The results from this study suggest flow effects may have limited impact on many PET neuroreceptor tracers with similar properties.

Assessment of myocardial metabolic rate of glucose by means of Bayesian ICA and Markov Chain Monte Carlo methods in small animal PET imaging

NASA Astrophysics Data System (ADS)

Berradja, Khadidja; Boughanmi, Nabil

2016-09-01

In dynamic cardiac PET FDG studies the assessment of myocardial metabolic rate of glucose (MMRG) requires the knowledge of the blood input function (IF). IF can be obtained by manual or automatic blood sampling and cross calibrated with PET. These procedures are cumbersome, invasive and generate uncertainties. The IF is contaminated by spillover of radioactivity from the adjacent myocardium and this could cause important error in the estimated MMRG. In this study, we show that the IF can be extracted from the images in a rat heart study with 18F-fluorodeoxyglucose (18F-FDG) by means of Independent Component Analysis (ICA) based on Bayesian theory and Markov Chain Monte Carlo (MCMC) sampling method (BICA). Images of the heart from rats were acquired with the Sherbrooke small animal PET scanner. A region of interest (ROI) was drawn around the rat image and decomposed into blood and tissue using BICA. The Statistical study showed that there is a significant difference (p < 0.05) between MMRG obtained with IF extracted by BICA with respect to IF extracted from measured images corrupted with spillover.

Policies on pets for healthy cities: a conceptual framework.

PubMed

Rock, Melanie J; Adams, Cindy L; Degeling, Chris; Massolo, Alessandro; McCormack, Gavin R

2015-12-01

Drawing on the One Health concept, and integrating a dual focus on public policy and practices of caring from the Ottawa Charter for Health Promotion, we outline a conceptual framework to help guide the development and assessment of local governments' policies on pets. This framework emphasizes well-being in human populations, while recognizing that these outcomes relate to the well-being of non-human animals. Five intersecting spheres of activity, each associated with local governments' jurisdiction over pets, are presented: (i) preventing threats and nuisances from pets, (ii) meeting pets' emotional and physical needs, (iii) procuring pets ethically, (iv) providing pets with veterinary services and (v) licensing and identifying pets. This conceptual framework acknowledges the tenets of previous health promotion frameworks, including overlapping and intersecting influences. At the same time, this framework proposes to advance our understanding of health promotion and, more broadly, population health by underscoring interdependence between people and pets as well as the dynamism of urbanized ecologies. © The Author (2014). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Long-term change of potential evapotranspiration over Southwest China and teleconnections with large-scale climate anomalies

NASA Astrophysics Data System (ADS)

Liu, B.; Chen, X.; Li, Y.; Chen, Z.

2017-12-01

bstract: Potential evapotranspiration (PET) is a sensitive factor for atmospheric and ecological systems over Southwest China which is characterized by intensive karst geomorphology and fragile environment. Based on daily meteorological data of 94 stations during 1961-2013, the spatiotemporal characteristics of PET are analyzed. The changing characteristics of local meteorological factors and large-scale climatic features are also investigated to explain the potential reasons for changing PET. Study results are as follows: (1) The high-value center of PET with a mean value of 1097 mm/a locates in the south mainly resulted from the regional climatic features of higher air temperature (TEM), sunshine duration (SSD) and lower relative humidity (RHU); and the low-value center of PET with a mean value of 831 mm/a is in the northeast primarily attributed to higher RHU and weaker SSD. (2) Annual PET decreases at -10.04 mm decade-1 before the year 2000 but increases at 50.65 mm decade-1 thereafter; and the dominant factors of PET change are SSD, RHU and wind speed (WIN), with the relative contributions of 33.29%, 25.42% and 22.16%, respectively. (3) The abrupt change of PET in 2000 is strongly dominated by large-scale climatic anomalies. The strengthened 850hPa geostrophic wind (0.51 ms-1 decade-1), weakened total cloud cover (-2.25 % decade-1) and 500hPa water vapor flux (-2.85 % decade-1) have provided advantageous dynamic, thermal and dry conditions for PET over Southwest China since the 21st century.

Imaging Bone–Cartilage Interactions in Osteoarthritis Using [18F]-NaF PET-MRI

PubMed Central

Pedoia, Valentina; Seo, Youngho; Yang, Jaewon; Bucknor, Matt; Franc, Benjamin L.; Majumdar, Sharmila

2016-01-01

Purpose: Simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI) is an emerging technology providing both anatomical and functional images without increasing the scan time. Compared to the traditional PET/computed tomography imaging, it also exposes the patient to significantly less radiation and provides better anatomical images as MRI provides superior soft tissue characterization. Using PET-MRI, we aim to study interactions between cartilage composition and bone function simultaneously, in knee osteoarthritis (OA). Procedures: In this article, bone turnover and remodeling was studied using [18F]-sodium fluoride (NaF) PET data. Quantitative MR-derived T1ρ relaxation times characterized the biochemical cartilage degeneration. Sixteen participants with early signs of OA of the knee received intravenous injections of [18F]-NaF at the onset of PET-MR image acquisition. Regions of interest were identified, and kinetic analysis of dynamic PET data provided the rate of uptake (Ki) and the normalized uptake (standardized uptake value) of [18F]-NaF in the bone. Morphological MR images and quantitative voxel-based T1ρ maps of cartilage were obtained using an atlas-based registration technique to segment cartilage automatically. Voxel-by-voxel statistical parameter mapping was used to investigate the relationship between bone and cartilage. Results: Increases in cartilage T1ρ, indicating degenerative changes, were associated with increased turnover in the adjoining bone but reduced turnover in the nonadjoining compartments. Associations between pain and increased bone uptake were seen in the absence of morphological lesions in cartilage, but the relationship was reversed in the presence of incident cartilage lesions. Conclusion: This study shows significant cartilage and bone interactions in OA of the knee joint using simultaneous [18F]-NaF PET-MR, the first in human study. These observations highlight the complex biomechanical and biochemical interactions in the whole knee joint in OA, which potentially could help assess therapeutic targets in treating OA. PMID:28654417

Patient educational technologies and their use by patients diagnosed with localized prostate cancer.

PubMed

Baverstock, Richard J; Crump, R Trafford; Carlson, Kevin V

2015-09-29

Two urology practices in Calgary, Canada use patient educational technology (PET) as a core component of their clinical practice. The purpose of this study was to determine how patients interact with PET designed to inform them about their treatment options for clinically localized prostate cancer. A PET library was developed with 15 unique prostate-related educational modules relating to diagnosis, treatment options, and potential side effects. The PET collected data regarding its use, and those data were used to conduct a retrospective analysis. Descriptive analyses were conducted and comparisons made between patients' utilization of the PET library during first and subsequent access; Pearson's Chi-Square was used to test for statistical significance, where appropriate. Every patient (n = 394) diagnosed with localized prostate cancer was given access to the PET library using a unique identifier. Of those, 123 logged into the library and viewed at least one module and 94 patients logged into the library more than once. The average patient initially viewed modules pertaining to their diagnosis. Viewing behavior significantly changed in subsequent logins, moving towards modules pertaining to treatment options, decision making, and post-surgical information. As observed through the longitudinal utilization of the PET library, information technology offers clinicians an opportunity to provide an interactive platform to meet patients' dynamic educational needs. Understanding these needs will help inform the development of more useful PETs. The informational needs of patients diagnosed with clinically localized prostate cancer changed throughout the course of their diagnosis and treatment.

Nonparametric Residue Analysis of Dynamic PET Data With Application to Cerebral FDG Studies in Normals.

PubMed

O'Sullivan, Finbarr; Muzi, Mark; Spence, Alexander M; Mankoff, David M; O'Sullivan, Janet N; Fitzgerald, Niall; Newman, George C; Krohn, Kenneth A

2009-06-01

Kinetic analysis is used to extract metabolic information from dynamic positron emission tomography (PET) uptake data. The theory of indicator dilutions, developed in the seminal work of Meier and Zierler (1954), provides a probabilistic framework for representation of PET tracer uptake data in terms of a convolution between an arterial input function and a tissue residue. The residue is a scaled survival function associated with tracer residence in the tissue. Nonparametric inference for the residue, a deconvolution problem, provides a novel approach to kinetic analysis-critically one that is not reliant on specific compartmental modeling assumptions. A practical computational technique based on regularized cubic B-spline approximation of the residence time distribution is proposed. Nonparametric residue analysis allows formal statistical evaluation of specific parametric models to be considered. This analysis needs to properly account for the increased flexibility of the nonparametric estimator. The methodology is illustrated using data from a series of cerebral studies with PET and fluorodeoxyglucose (FDG) in normal subjects. Comparisons are made between key functionals of the residue, tracer flux, flow, etc., resulting from a parametric (the standard two-compartment of Phelps et al. 1979) and a nonparametric analysis. Strong statistical evidence against the compartment model is found. Primarily these differences relate to the representation of the early temporal structure of the tracer residence-largely a function of the vascular supply network. There are convincing physiological arguments against the representations implied by the compartmental approach but this is the first time that a rigorous statistical confirmation using PET data has been reported. The compartmental analysis produces suspect values for flow but, notably, the impact on the metabolic flux, though statistically significant, is limited to deviations on the order of 3%-4%. The general advantage of the nonparametric residue analysis is the ability to provide a valid kinetic quantitation in the context of studies where there may be heterogeneity or other uncertainty about the accuracy of a compartmental model approximation of the tissue residue.

MR-based motion correction for PET imaging using wired active MR microcoils in simultaneous PET-MR: Phantom study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chuan; Brady, Thomas J.; El Fakhri, Georges

2014-04-15

Purpose: Artifacts caused by head motion present a major challenge in brain positron emission tomography (PET) imaging. The authors investigated the feasibility of using wired active MR microcoils to track head motion and incorporate the measured rigid motion fields into iterative PET reconstruction. Methods: Several wired active MR microcoils and a dedicated MR coil-tracking sequence were developed. The microcoils were attached to the outer surface of an anthropomorphic{sup 18}F-filled Hoffman phantom to mimic a brain PET scan. Complex rotation/translation motion of the phantom was induced by a balloon, which was connected to a ventilator. PET list-mode and MR tracking datamore » were acquired simultaneously on a PET-MR scanner. The acquired dynamic PET data were reconstructed iteratively with and without motion correction. Additionally, static phantom data were acquired and used as the gold standard. Results: Motion artifacts in PET images were effectively removed by wired active MR microcoil based motion correction. Motion correction yielded an activity concentration bias ranging from −0.6% to 3.4% as compared to a bias ranging from −25.0% to 16.6% if no motion correction was applied. The contrast recovery values were improved by 37%–156% with motion correction as compared to no motion correction. The image correlation (mean ± standard deviation) between the motion corrected (uncorrected) images of 20 independent noise realizations and static reference was R{sup 2} = 0.978 ± 0.007 (0.588 ± 0.010, respectively). Conclusions: Wired active MR microcoil based motion correction significantly improves brain PET quantitative accuracy and image contrast.« less

MR-based motion correction for PET imaging using wired active MR microcoils in simultaneous PET-MR: Phantom study1

PubMed Central

Huang, Chuan; Ackerman, Jerome L.; Petibon, Yoann; Brady, Thomas J.; El Fakhri, Georges; Ouyang, Jinsong

2014-01-01

Purpose: Artifacts caused by head motion present a major challenge in brain positron emission tomography (PET) imaging. The authors investigated the feasibility of using wired active MR microcoils to track head motion and incorporate the measured rigid motion fields into iterative PET reconstruction. Methods: Several wired active MR microcoils and a dedicated MR coil-tracking sequence were developed. The microcoils were attached to the outer surface of an anthropomorphic 18F-filled Hoffman phantom to mimic a brain PET scan. Complex rotation/translation motion of the phantom was induced by a balloon, which was connected to a ventilator. PET list-mode and MR tracking data were acquired simultaneously on a PET-MR scanner. The acquired dynamic PET data were reconstructed iteratively with and without motion correction. Additionally, static phantom data were acquired and used as the gold standard. Results: Motion artifacts in PET images were effectively removed by wired active MR microcoil based motion correction. Motion correction yielded an activity concentration bias ranging from −0.6% to 3.4% as compared to a bias ranging from −25.0% to 16.6% if no motion correction was applied. The contrast recovery values were improved by 37%–156% with motion correction as compared to no motion correction. The image correlation (mean ± standard deviation) between the motion corrected (uncorrected) images of 20 independent noise realizations and static reference was R2 = 0.978 ± 0.007 (0.588 ± 0.010, respectively). Conclusions: Wired active MR microcoil based motion correction significantly improves brain PET quantitative accuracy and image contrast. PMID:24694141

The SAFIR experiment: Concept, status and perspectives

NASA Astrophysics Data System (ADS)

Becker, Robert; Buck, Alfred; Casella, Chiara; Dissertori, Günther; Fischer, Jannis; Howard, Alexander; Ito, Mikiko; Khateri, Parisa; Lustermann, Werner; Oliver, Josep F.; Röser, Ulf; Warnock, Geoffrey; Weber, Bruno

2017-02-01

The SAFIR development represents a novel Positron Emission Tomography (PET) detector, conceived for preclinical fast acquisitions inside the bore of a Magnetic Resonance Imaging (MRI) scanner. The goal is hybrid and simultaneous PET/MRI dynamic studies at unprecedented temporal resolutions of a few seconds. The detector relies on matrices of scintillating LSO-based crystals coupled one-to-one with SiPM arrays and readout by fast ASICs with excellent timing resolution and high rate capabilities. The paper describes the detector concept and the initial results in terms of simulations and characterisation measurements.

Quantitation of benzodiazepine receptor binding with PET [11C]iomazenil and SPECT [123I]iomazenil: preliminary results of a direct comparison in healthy human subjects.

PubMed

Bremner, J D; Baldwin, R; Horti, A; Staib, L H; Ng, C K; Tan, P Z; Zea-Ponce, Y; Zoghbi, S; Seibyl, J P; Soufer, R; Charney, D S; Innis, R B

1999-08-31

Although positron emission tomography (PET) and single photon emission computed tomography (SPECT) are increasingly used for quantitation of neuroreceptor binding, almost no studies to date have involved a direct comparison of the two. One study found a high level of agreement between the two techniques, although there was a systematic 30% increase in measures of benzodiazepine receptor binding in SPECT compared with PET. The purpose of the current study was to directly compare quantitation of benzodiazepine receptor binding in the same human subjects using PET and SPECT with high specific activity [11C]iomazenil and [123I]iomazenil, respectively. All subjects were administered a single bolus of high specific activity iomazenil labeled with 11C or 123I followed by dynamic PET or SPECT imaging of the brain. Arterial blood samples were obtained for measurement of metabolite-corrected radioligand in plasma. Compartmental modeling was used to fit values for kinetic rate constants of transfer of radioligand between plasma and brain compartments. These values were used for calculation of binding potential (BP = Bmax/Kd) and product of BP and the fraction of free non-protein-bound parent compound (V3'). Mean values for V3' in PET and SPECT were as follows: temporal cortex 23+/-5 and 22+/-3 ml/g, frontal cortex23+/-6 and 22+/-3 ml/g, occipital cortex 28+/-3 and 31+/-5 ml/g, and striatum 4+/-4 and 7+/-4 ml/g. These preliminary findings indicate that PET and SPECT provide comparable results in quantitation of neuroreceptor binding in the human brain.

SBML-PET-MPI: a parallel parameter estimation tool for Systems Biology Markup Language based models.

PubMed

Zi, Zhike

2011-04-01

Parameter estimation is crucial for the modeling and dynamic analysis of biological systems. However, implementing parameter estimation is time consuming and computationally demanding. Here, we introduced a parallel parameter estimation tool for Systems Biology Markup Language (SBML)-based models (SBML-PET-MPI). SBML-PET-MPI allows the user to perform parameter estimation and parameter uncertainty analysis by collectively fitting multiple experimental datasets. The tool is developed and parallelized using the message passing interface (MPI) protocol, which provides good scalability with the number of processors. SBML-PET-MPI is freely available for non-commercial use at http://www.bioss.uni-freiburg.de/cms/sbml-pet-mpi.html or http://sites.google.com/site/sbmlpetmpi/.

PET motion correction in context of integrated PET/MR: Current techniques, limitations, and future projections.

PubMed

Gillman, Ashley; Smith, Jye; Thomas, Paul; Rose, Stephen; Dowson, Nicholas

2017-12-01

Patient motion is an important consideration in modern PET image reconstruction. Advances in PET technology mean motion has an increasingly important influence on resulting image quality. Motion-induced artifacts can have adverse effects on clinical outcomes, including missed diagnoses and oversized radiotherapy treatment volumes. This review aims to summarize the wide variety of motion correction techniques available in PET and combined PET/CT and PET/MR, with a focus on the latter. A general framework for the motion correction of PET images is presented, consisting of acquisition, modeling, and correction stages. Methods for measuring, modeling, and correcting motion and associated artifacts, both in literature and commercially available, are presented, and their relative merits are contrasted. Identified limitations of current methods include modeling of aperiodic and/or unpredictable motion, attaining adequate temporal resolution for motion correction in dynamic kinetic modeling acquisitions, and maintaining availability of the MR in PET/MR scans for diagnostic acquisitions. Finally, avenues for future investigation are discussed, with a focus on improvements that could improve PET image quality, and that are practical in the clinical environment. © 2017 American Association of Physicists in Medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.

We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits themore » utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.« less

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2017-01-01

To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV max . Mean overall survival showed a significant difference for total perfusion (p=0.003) and systemic arterial perfusion (p=0.04). Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

NASA Astrophysics Data System (ADS)

Avendaño-Estrada, A.; Lara-Camacho, V. M.; Ávila-García, M. C.; Ávila-Rodríguez, M. A.

2014-11-01

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [11C ]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avendaño-Estrada, A., E-mail: avilarod@uwalumni.com; Lara-Camacho, V. M., E-mail: avilarod@uwalumni.com; Ávila-García, M. C., E-mail: avilarod@uwalumni.com

2014-11-07

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [{sup 11}C]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Imaging and dosimetric errors in 4D PET/CT-guided radiotherapy from patient-specific respiratory patterns: a dynamic motion phantom end-to-end study

NASA Astrophysics Data System (ADS)

Bowen, S. R.; Nyflot, M. J.; Herrmann, C.; Groh, C. M.; Meyer, J.; Wollenweber, S. D.; Stearns, C. W.; Kinahan, P. E.; Sandison, G. A.

2015-05-01

Effective positron emission tomography / computed tomography (PET/CT) guidance in radiotherapy of lung cancer requires estimation and mitigation of errors due to respiratory motion. An end-to-end workflow was developed to measure patient-specific motion-induced uncertainties in imaging, treatment planning, and radiation delivery with respiratory motion phantoms and dosimeters. A custom torso phantom with inserts mimicking normal lung tissue and lung lesion was filled with [18F]FDG. The lung lesion insert was driven by six different patient-specific respiratory patterns or kept stationary. PET/CT images were acquired under motionless ground truth, tidal breathing motion-averaged (3D), and respiratory phase-correlated (4D) conditions. Target volumes were estimated by standardized uptake value (SUV) thresholds that accurately defined the ground-truth lesion volume. Non-uniform dose-painting plans using volumetrically modulated arc therapy were optimized for fixed normal lung and spinal cord objectives and variable PET-based target objectives. Resulting plans were delivered to a cylindrical diode array at rest, in motion on a platform driven by the same respiratory patterns (3D), or motion-compensated by a robotic couch with an infrared camera tracking system (4D). Errors were estimated relative to the static ground truth condition for mean target-to-background (T/Bmean) ratios, target volumes, planned equivalent uniform target doses, and 2%-2 mm gamma delivery passing rates. Relative to motionless ground truth conditions, PET/CT imaging errors were on the order of 10-20%, treatment planning errors were 5-10%, and treatment delivery errors were 5-30% without motion compensation. Errors from residual motion following compensation methods were reduced to 5-10% in PET/CT imaging, <5% in treatment planning, and <2% in treatment delivery. We have demonstrated that estimation of respiratory motion uncertainty and its propagation from PET/CT imaging to RT planning, and RT delivery under a dose painting paradigm is feasible within an integrated respiratory motion phantom workflow. For a limited set of cases, the magnitude of errors was comparable during PET/CT imaging and treatment delivery without motion compensation. Errors were moderately mitigated during PET/CT imaging and significantly mitigated during RT delivery with motion compensation. This dynamic motion phantom end-to-end workflow provides a method for quality assurance of 4D PET/CT-guided radiotherapy, including evaluation of respiratory motion compensation methods during imaging and treatment delivery.

Imaging and dosimetric errors in 4D PET/CT-guided radiotherapy from patient-specific respiratory patterns: a dynamic motion phantom end-to-end study.

PubMed

Bowen, S R; Nyflot, M J; Herrmann, C; Groh, C M; Meyer, J; Wollenweber, S D; Stearns, C W; Kinahan, P E; Sandison, G A

2015-05-07

Effective positron emission tomography / computed tomography (PET/CT) guidance in radiotherapy of lung cancer requires estimation and mitigation of errors due to respiratory motion. An end-to-end workflow was developed to measure patient-specific motion-induced uncertainties in imaging, treatment planning, and radiation delivery with respiratory motion phantoms and dosimeters. A custom torso phantom with inserts mimicking normal lung tissue and lung lesion was filled with [(18)F]FDG. The lung lesion insert was driven by six different patient-specific respiratory patterns or kept stationary. PET/CT images were acquired under motionless ground truth, tidal breathing motion-averaged (3D), and respiratory phase-correlated (4D) conditions. Target volumes were estimated by standardized uptake value (SUV) thresholds that accurately defined the ground-truth lesion volume. Non-uniform dose-painting plans using volumetrically modulated arc therapy were optimized for fixed normal lung and spinal cord objectives and variable PET-based target objectives. Resulting plans were delivered to a cylindrical diode array at rest, in motion on a platform driven by the same respiratory patterns (3D), or motion-compensated by a robotic couch with an infrared camera tracking system (4D). Errors were estimated relative to the static ground truth condition for mean target-to-background (T/Bmean) ratios, target volumes, planned equivalent uniform target doses, and 2%-2 mm gamma delivery passing rates. Relative to motionless ground truth conditions, PET/CT imaging errors were on the order of 10-20%, treatment planning errors were 5-10%, and treatment delivery errors were 5-30% without motion compensation. Errors from residual motion following compensation methods were reduced to 5-10% in PET/CT imaging, <5% in treatment planning, and <2% in treatment delivery. We have demonstrated that estimation of respiratory motion uncertainty and its propagation from PET/CT imaging to RT planning, and RT delivery under a dose painting paradigm is feasible within an integrated respiratory motion phantom workflow. For a limited set of cases, the magnitude of errors was comparable during PET/CT imaging and treatment delivery without motion compensation. Errors were moderately mitigated during PET/CT imaging and significantly mitigated during RT delivery with motion compensation. This dynamic motion phantom end-to-end workflow provides a method for quality assurance of 4D PET/CT-guided radiotherapy, including evaluation of respiratory motion compensation methods during imaging and treatment delivery.

Imaging and dosimetric errors in 4D PET/CT-guided radiotherapy from patient-specific respiratory patterns: a dynamic motion phantom end-to-end study

PubMed Central

Bowen, S R; Nyflot, M J; Hermann, C; Groh, C; Meyer, J; Wollenweber, S D; Stearns, C W; Kinahan, P E; Sandison, G A

2015-01-01

Effective positron emission tomography/computed tomography (PET/CT) guidance in radiotherapy of lung cancer requires estimation and mitigation of errors due to respiratory motion. An end-to-end workflow was developed to measure patient-specific motion-induced uncertainties in imaging, treatment planning, and radiation delivery with respiratory motion phantoms and dosimeters. A custom torso phantom with inserts mimicking normal lung tissue and lung lesion was filled with [18F]FDG. The lung lesion insert was driven by 6 different patient-specific respiratory patterns or kept stationary. PET/CT images were acquired under motionless ground truth, tidal breathing motion-averaged (3D), and respiratory phase-correlated (4D) conditions. Target volumes were estimated by standardized uptake value (SUV) thresholds that accurately defined the ground-truth lesion volume. Non-uniform dose-painting plans using volumetrically modulated arc therapy (VMAT) were optimized for fixed normal lung and spinal cord objectives and variable PET-based target objectives. Resulting plans were delivered to a cylindrical diode array at rest, in motion on a platform driven by the same respiratory patterns (3D), or motion-compensated by a robotic couch with an infrared camera tracking system (4D). Errors were estimated relative to the static ground truth condition for mean target-to-background (T/Bmean) ratios, target volumes, planned equivalent uniform target doses (EUD), and 2%-2mm gamma delivery passing rates. Relative to motionless ground truth conditions, PET/CT imaging errors were on the order of 10–20%, treatment planning errors were 5–10%, and treatment delivery errors were 5–30% without motion compensation. Errors from residual motion following compensation methods were reduced to 5–10% in PET/CT imaging, < 5% in treatment planning, and < 2% in treatment delivery. We have demonstrated that estimation of respiratory motion uncertainty and its propagation from PET/CT imaging to RT planning, and RT delivery under a dose painting paradigm is feasible within an integrated respiratory motion phantom workflow. For a limited set of cases, the magnitude of errors was comparable during PET/CT imaging and treatment delivery without motion compensation. Errors were moderately mitigated during PET/CT imaging and significantly mitigated during RT delivery with motion compensation. This dynamic motion phantom end-to-end workflow provides a method for quality assurance of 4D PET/CT-guided radiotherapy, including evaluation of respiratory motion compensation methods during imaging and treatment delivery. PMID:25884892

An approach to the usage of polyethylene terephthalate (PET) waste as roadway pavement material.

PubMed

Gürü, Metin; Çubuk, M Kürşat; Arslan, Deniz; Farzanian, S Ali; Bilici, İbrahim

2014-08-30

This study investigates an application area for Polyethylene Terephthalate (PET) bottle waste which has become an environmental problem in recent decades as being a considerable part of the total plastic waste bulk. Two novel additive materials, namely Thin Liquid Polyol PET (TLPP) and Viscous Polyol PET (VPP), were chemically derived from waste PET bottles and used to modify the base asphalt separately for this aim. The effects of TLPP and VPP on the asphalt and hot mix asphalt (HMA) mixture properties were detected through conventional tests (Penetration, Softening Point, Ductility, Marshall Stability, Nicholson Stripping) and Superpave methods (Rotational Viscosity, Dynamic Shear Rheometer (DSR), Bending Beam Rheometer (BBR)). Also, chemical structures were described by Scanning Electron Microscope (SEM) equipped with Energy Dispersive Spectrometer (EDS) and Fourier Transform Infrared (FTIR) techniques. Since TLPP and VPP were determined to improve the low temperature performance and fatigue resistance of the asphalt as well as the Marshall Stability and stripping resistance of the HMA mixtures based on the results of the applied tests, the usage of PET waste as an asphalt roadway pavement material offers an alternative and a beneficial way of disposal of this ecologically hazardous material. Copyright © 2014 Elsevier B.V. All rights reserved.

Sweet Polymers: Poly(2-ethyl-2-oxazoline) Glycopolymers by Reductive Amination.

PubMed

Mees, Maarten A; Effenberg, Christiane; Appelhans, Dietmar; Hoogenboom, Richard

2016-12-12

Carbohydrates are important in signaling, energy storage, and metabolism. Depending on their function, carbohydrates can be part of larger structures, such as glycoproteins, glycolipids, or other functionalities (glycoside). To this end, polymers can act as carriers of carbohydrates in so-called glycopolymers, which mimic the multivalent carbohydrate functionalities. We chose a biocompatible poly(2-ethyl-2-oxazoline) (PEtOx) as the basis for making glycopolymers. Via the partial hydrolysis of PEtOx, a copolymer of PEtOx and polyethylenimine (PEI) was obtained; the subsequent reductive amination with the linear forms of glucose and maltose yielded the glycopolymers. The ratios of PEtOx and carbohydrates were varied systematically, and the solution behaviors of the resulting glycoconjugates are discussed. Dynamic light scattering (DLS) revealed that, depending on the carbohydrate ratio, the glycopolymers were either fully water-soluble or formed agglomerates in a temperature-dependent manner. Finally, these polymers were tested for their biological availability by studying their lectin binding ability with Concanavalin A.

The Road to the Common PET/CT Detector

NASA Astrophysics Data System (ADS)

Nassalski, Antoni; Moszynski, Marek; Szczesniak, Tomasz; Wolski, Dariusz; Batsch, Tadeusz

2007-10-01

Growing interest in the development of dual modality positron emission/X-rays tomography (PET/CT) systems prompts researchers to face a new challenge: to acquire both the anatomical and functional information in the same measurement, simultaneously using the same detection system and electronics. The aim of this work was to study a detector consisting of LaBr3, LSO or LYSO pixel crystals coupled to an avalanche photodiode (APD). The measurements covered tests of the detectors in PET and CT modes, respectively. The measurements included the determination of light output, energy resolution, the non-proportionality of the light yield and the time resolution for 511 keV annihilation quanta; analysis also included characterizing the PET detector, and determining the dependence of counting rate versus mean current of the APD in the X-ray detection. In the present experiment, the use of counting and current modes in the CT detection increases the dynamic range of the measured dose of X-rays by a factor of 20, compared to the counting mode alone.

Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study.

PubMed

Derlin, Thorsten; Tóth, Zoltán; Papp, László; Wisotzki, Christian; Apostolova, Ivayla; Habermann, Christian R; Mester, Janos; Klutmann, Susanne

2011-07-01

Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by (18)F-FDG PET and ongoing mineral deposition as measured by (18)F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Forty-five patients were examined by whole-body (18)F-FDG PET, (18)F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r(s) were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. (18)F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. (18)F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked (18)F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with (18)F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both (18)F-sodium fluoride and (18)F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. PET/CT with (18)F-FDG and (18)F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation

DOE PAGES

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares; ...

2015-12-29

The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curvemore » K 1 = F(1–Aexp(–B/F)) for K 1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. The estimated flow-extraction parameters for 99mTc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99mTc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.« less

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation.

PubMed

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares; Yeghiazarians, Yerem; Ellin, Justin; Verdin, Emily; Boyle, Andrew; Seo, Youngho; Botvinick, Elias H; Gullberg, Grant T

2017-02-01

The objective of this study was to measure myocardial blood flow (MBF) in humans using 99m Tc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Dynamic SPECT using 99m Tc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99m Tc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99m Tc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve [Formula: see text] for K 1 values estimated with 99m Tc-tefrofosmin using SPECT and MBF values estimated with 13 N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13 N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99m Tc-tefrofosmin was also estimated. The estimated flow-extraction parameters for 99m Tc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2  = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99m Tc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). Dynamic cardiac SPECT using 99m Tc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.

Measurement of Absolute Myocardial Blood Flow in Humans Using Dynamic Cardiac SPECT and 99mTc-tetrofosmin: Method and Validation

PubMed Central

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares; Yeghiazarians, Yerem; Ellin, Justin; Verdin, Emily; Boyle, Andrew; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

2015-01-01

Background The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single photon emission computed tomography (SPECT). Methods Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve K1=F(1−Aexp(−BF)) for K1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH3 PET. The flow dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. Results The estimated flow extraction parameters for 99mTc-tefrofosmin was found to be A=0.91±0.11, B=0.34±0.20 (R2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The PS for 99mTc-tefrofosmin was (0.091 ± 0.10) * MBF = (0.32 ± 0.16). Conclusions Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF. PMID:26715603

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares

The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curvemore » K 1 = F(1–Aexp(–B/F)) for K 1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. The estimated flow-extraction parameters for 99mTc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99mTc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.« less

Modeling of FMISO [F18] nanoparticle PET tracer in normal-cancerous tissue based on real clinical image.

PubMed

Asgari, Hanie; Soltani, M; Sefidgar, Mostafa

2018-07-01

Hypoxia as one of the principal properties of tumor cells is a reaction to the deprivation of oxygen. The location of tumor cells could be identified by assessment of oxygen and nutrient level in human body. Positron emission tomography (PET) is a well-known non-invasive method that is able to measure hypoxia based on the FMISO (Fluoromisonidazole) tracer dynamic. This paper aims to study the PET tracer concentration through convection-diffusion-reaction equations in a real human capillary-like network. A non-uniform oxygen pressure along the capillary path and convection mechanism for FMISO transport are taken into account to accurately model the characteristics of the tracer. To this end, a multi-scale model consists of laminar blood flow through the capillary network, interstitial pressure, oxygen pressure, FMISO diffusion and FMISO convection transport in the extravascular region is developed. The present model considers both normal and tumor tissue regions in computational domain. The accuracy of numerical model is verified with the experimental results available in the literature. The convection and diffusion types of transport mechanism are employed in order to calculate the concentration of FMISO in the normal and tumor sub-domain. The influences of intravascular oxygen pressure, FMISO transport mechanisms, capillary density and different types of tissue on the FMISO concentration have been investigated. According to result (Table 4) the convection mechanism of FMISO molecules transportation is negligible, but it causes more accuracy of the proposed model. The approach of present study can be employed in order to investigate the effects of various parameters, such as tumor shape, on the dynamic behavior of different PET tracers, such as FDG, can be extended to different case study problems, such as drug delivery. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement of regional cerebral blood flow with copper-62-PTSM and a three-compartment model.

PubMed

Okazawa, H; Yonekura, Y; Fujibayashi, Y; Mukai, T; Nishizawa, S; Magata, Y; Ishizu, K; Tamaki, N; Konishi, J

1996-07-01

We evaluated quantitatively 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) as a brain perfusion tracer for positron emission tomography (PET). For quantitative measurement, the octanol extraction method is needed to correct for arterial radioactivity in estimating the lipophilic input function, but the procedure is not practical for clinical studies. To measure regional cerebral blood flow (rCBF) by 62Cu-PTSM with simple arterial blood sampling, a standard curve of the octanol extraction ratio and a three-compartment model were applied. We performed both 15O-labeled water PET and 62 Cu-PTSM PET with dynamic data acquisition and arterial sampling in six subjects. Data obtained in 10 subjects studied previously were used for the standard octanol extraction curve. Arterial activity was measured and corrected to obtain the true input function using the standard curve. Graphical analysis (Gjedde-Patlak plot) with the data for each subject fitted by a straight regression line suggested that 62Cu-PTSM can be analyzed by the three-compartment model with negligible K4. Using this model, K1-K3 were estimated from curve fitting of the cerebral time-activity curve and the corrected input function. The fractional uptake of 62Cu-PTSM was corrected to rCBF with the individual extraction at steady state calculated from K1-K3. The influx rates (Ki) obtained from three-compartment model and graphical analyses were compared for the validation of the model. A comparison of rCBF values obtained from 62Cu-PTSM and 150-water studies demonstrated excellent correlation. The results suggest the potential feasibility of quantitation of cerebral perfusion with 62Cu-PTSM accompanied by dynamic PET and simple arterial sampling.

Multi-modality imaging of tumor phenotype and response to therapy

NASA Astrophysics Data System (ADS)

Nyflot, Matthew J.

2011-12-01

Imaging and radiation oncology have historically been closely linked. However, the vast majority of techniques used in the clinic involve anatomical imaging. Biological imaging offers the potential for innovation in the areas of cancer diagnosis and staging, radiotherapy target definition, and treatment response assessment. Some relevant imaging techniques are FDG PET (for imaging cellular metabolism), FLT PET (proliferation), CuATSM PET (hypoxia), and contrast-enhanced CT (vasculature and perfusion). Here, a technique for quantitative spatial correlation of tumor phenotype is presented for FDG PET, FLT PET, and CuATSM PET images. Additionally, multimodality imaging of treatment response with FLT PET, CuATSM, and dynamic contrast-enhanced CT is presented, in a trial of patients receiving an antiangiogenic agent (Avastin) combined with cisplatin and radiotherapy. Results are also presented for translational applications in animal models, including quantitative assessment of proliferative response to cetuximab with FLT PET and quantification of vascular volume with a blood-pool contrast agent (Fenestra). These techniques have clear applications to radiobiological research and optimized treatment strategies, and may eventually be used for personalized therapy for patients.

Active Site Flexibility as a Hallmark for Efficient PET Degradation by I. sakaiensis PETase.

PubMed

Fecker, Tobias; Galaz-Davison, Pablo; Engelberger, Felipe; Narui, Yoshie; Sotomayor, Marcos; Parra, Loreto P; Ramírez-Sarmiento, César A

2018-03-27

Polyethylene terephthalate (PET) is one of the most-consumed synthetic polymers, with an annual production of 50 million tons. Unfortunately, PET accumulates as waste and is highly resistant to biodegradation. Recently, fungal and bacterial thermophilic hydrolases were found to catalyze PET hydrolysis with optimal activities at high temperatures. Strikingly, an enzyme from Ideonella sakaiensis, termed PETase, was described to efficiently degrade PET at room temperature, but the molecular basis of its activity is not currently understood. Here, a crystal structure of PETase was determined at 2.02 Å resolution and employed in molecular dynamics simulations showing that the active site of PETase has higher flexibility at room temperature than its thermophilic counterparts. This flexibility is controlled by a novel disulfide bond in its active site, with its removal leading to destabilization of the catalytic triad and reduction of the hydrolase activity. Molecular docking of a model substrate predicts that PET binds to PETase in a unique and energetically favorable conformation facilitated by several residue substitutions within its active site when compared to other enzymes. These computational predictions are in excellent agreement with recent mutagenesis and PET film degradation analyses. Finally, we rationalize the increased catalytic activity of PETase at room temperature through molecular dynamics simulations of enzyme-ligand complexes for PETase and other thermophilic PET-degrading enzymes at 298, 323, and 353 K. Our results reveal that both the binding pose and residue substitutions within PETase favor proximity between the catalytic residues and the labile carbonyl of the substrate at room temperature, suggesting a more favorable hydrolytic reaction. These results are valuable for enabling detailed evolutionary analysis of PET-degrading enzymes and for rational design endeavors aiming at increasing the efficiency of PETase and similar enzymes toward plastic degradation. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Regional metabolic liver function measured in patients with cirrhosis by 2-[¹⁸F]fluoro-2-deoxy-D-galactose PET/CT.

PubMed

Sørensen, Michael; Mikkelsen, Kasper S; Frisch, Kim; Villadsen, Gerda E; Keiding, Susanne

2013-06-01

There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[(18)F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick's principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (p<0.001), in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for Kmet in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p<0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p<0.05). A 20-min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Patient motion effects on the quantification of regional myocardial blood flow with dynamic PET imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunter, Chad R. R. N.; Kemp, Robert A. de, E-mail: RAdeKemp@ottawaheart.ca; Klein, Ran

Purpose: Patient motion is a common problem during dynamic positron emission tomography (PET) scans for quantification of myocardial blood flow (MBF). The purpose of this study was to quantify the prevalence of body motion in a clinical setting and evaluate with realistic phantoms the effects of motion on blood flow quantification, including CT attenuation correction (CTAC) artifacts that result from PET–CT misalignment. Methods: A cohort of 236 sequential patients was analyzed for patient motion under resting and peak stress conditions by two independent observers. The presence of motion, affected time-frames, and direction of motion was recorded; discrepancy between observers wasmore » resolved by consensus review. Based on these results, patient body motion effects on MBF quantification were characterized using the digital NURBS-based cardiac-torso phantom, with characteristic time activity curves (TACs) assigned to the heart wall (myocardium) and blood regions. Simulated projection data were corrected for attenuation and reconstructed using filtered back-projection. All simulations were performed without noise added, and a single CT image was used for attenuation correction and aligned to the early- or late-frame PET images. Results: In the patient cohort, mild motion of 0.5 ± 0.1 cm occurred in 24% and moderate motion of 1.0 ± 0.3 cm occurred in 38% of patients. Motion in the superior/inferior direction accounted for 45% of all detected motion, with 30% in the superior direction. Anterior/posterior motion was predominant (29%) in the posterior direction. Left/right motion occurred in 24% of cases, with similar proportions in the left and right directions. Computer simulation studies indicated that errors in MBF can approach 500% for scans with severe patient motion (up to 2 cm). The largest errors occurred when the heart wall was shifted left toward the adjacent lung region, resulting in a severe undercorrection for attenuation of the heart wall. Simulations also indicated that the magnitude of MBF errors resulting from motion in the superior/inferior and anterior/posterior directions was similar (up to 250%). Body motion effects were more detrimental for higher resolution PET imaging (2 vs 10 mm full-width at half-maximum), and for motion occurring during the mid-to-late time-frames. Motion correction of the reconstructed dynamic image series resulted in significant reduction in MBF errors, but did not account for the residual PET–CTAC misalignment artifacts. MBF bias was reduced further using global partial-volume correction, and using dynamic alignment of the PET projection data to the CT scan for accurate attenuation correction during image reconstruction. Conclusions: Patient body motion can produce MBF estimation errors up to 500%. To reduce these errors, new motion correction algorithms must be effective in identifying motion in the left/right direction, and in the mid-to-late time-frames, since these conditions produce the largest errors in MBF, particularly for high resolution PET imaging. Ideally, motion correction should be done before or during image reconstruction to eliminate PET-CTAC misalignment artifacts.« less

Parametric Method Performance for Dynamic 3'-Deoxy-3'-18F-Fluorothymidine PET/CT in Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Carcinoma Patients Before and During Therapy.

PubMed

Kramer, Gerbrand Maria; Frings, Virginie; Heijtel, Dennis; Smit, E F; Hoekstra, Otto S; Boellaard, Ronald

2017-06-01

The objective of this study was to validate several parametric methods for quantification of 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) PET in advanced-stage non-small cell lung carcinoma (NSCLC) patients with an activating epidermal growth factor receptor mutation who were treated with gefitinib or erlotinib. Furthermore, we evaluated the impact of noise on accuracy and precision of the parametric analyses of dynamic 18 F-FLT PET/CT to assess the robustness of these methods. Methods : Ten NSCLC patients underwent dynamic 18 F-FLT PET/CT at baseline and 7 and 28 d after the start of treatment. Parametric images were generated using plasma input Logan graphic analysis and 2 basis functions-based methods: a 2-tissue-compartment basis function model (BFM) and spectral analysis (SA). Whole-tumor-averaged parametric pharmacokinetic parameters were compared with those obtained by nonlinear regression of the tumor time-activity curve using a reversible 2-tissue-compartment model with blood volume fraction. In addition, 2 statistically equivalent datasets were generated by countwise splitting the original list-mode data, each containing 50% of the total counts. Both new datasets were reconstructed, and parametric pharmacokinetic parameters were compared between the 2 replicates and the original data. Results: After the settings of each parametric method were optimized, distribution volumes (V T ) obtained with Logan graphic analysis, BFM, and SA all correlated well with those derived using nonlinear regression at baseline and during therapy ( R 2 ≥ 0.94; intraclass correlation coefficient > 0.97). SA-based V T images were most robust to increased noise on a voxel-level (repeatability coefficient, 16% vs. >26%). Yet BFM generated the most accurate K 1 values ( R 2 = 0.94; intraclass correlation coefficient, 0.96). Parametric K 1 data showed a larger variability in general; however, no differences were found in robustness between methods (repeatability coefficient, 80%-84%). Conclusion: Both BFM and SA can generate quantitatively accurate parametric 18 F-FLT V T images in NSCLC patients before and during therapy. SA was more robust to noise, yet BFM provided more accurate parametric K 1 data. We therefore recommend BFM as the preferred parametric method for analysis of dynamic 18 F-FLT PET/CT studies; however, SA can also be used. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Silk-based anisotropical 3D biotextiles for bone regeneration.

PubMed

Ribeiro, Viviana P; Silva-Correia, Joana; Nascimento, Ana I; da Silva Morais, Alain; Marques, Alexandra P; Ribeiro, Ana S; Silva, Carla J; Bonifácio, Graça; Sousa, Rui A; Oliveira, Joaquim M; Oliveira, Ana L; Reis, Rui L

2017-04-01

Bone loss in the craniofacial complex can been treated using several conventional therapeutic strategies that face many obstacles and limitations. In this work, novel three-dimensional (3D) biotextile architectures were developed as a possible strategy for flat bone regeneration applications. As a fully automated processing route, this strategy as potential to be easily industrialized. Silk fibroin (SF) yarns were processed into weft-knitted fabrics spaced by a monofilament of polyethylene terephthalate (PET). A comparative study with a similar 3D structure made entirely of PET was established. Highly porous scaffolds with homogeneous pore distribution were observed using micro-computed tomography analysis. The wet state dynamic mechanical analysis revealed a storage modulus In the frequency range tested, the storage modulus values obtained for SF-PET scaffolds were higher than for the PET scaffolds. Human adipose-derived stem cells (hASCs) cultured on the SF-PET spacer structures showed the typical pattern for ALP activity under osteogenic culture conditions. Osteogenic differentiation of hASCs on SF-PET and PET constructs was also observed by extracellular matrix mineralization and expression of osteogenic-related markers (osteocalcin, osteopontin and collagen type I) after 28 days of osteogenic culture, in comparison to the control basal medium. The quantification of convergent macroscopic blood vessels toward the scaffolds by a chick chorioallantoic membrane assay, showed higher angiogenic response induced by the SF-PET textile scaffolds than PET structures and gelatin sponge controls. Subcutaneous implantation in CD-1 mice revealed tissue ingrowth's accompanied by blood vessels infiltration in both spacer constructs. The structural adaptability of textile structures combined to the structural similarities of the 3D knitted spacer fabrics to craniofacial bone tissue and achieved biological performance, make these scaffolds a possible solution for tissue engineering approaches in this area. Copyright © 2017 Elsevier Ltd. All rights reserved.

PET imaging and biodistribution analysis of the effects of succinylated gelatin combined with L-lysine on renal uptake and retention of ⁶⁴Cu-cyclam-RAFT-c(-RGDfK-)₄ in vivo.

PubMed

Jin, Zhao-Hui; Furukawa, Takako; Sogawa, Chizuru; Claron, Michael; Aung, Winn; Tsuji, Atsushi B; Wakizaka, Hidekatsu; Zhang, Ming-Rong; Boturyn, Didier; Dumy, Pascal; Fujibayashi, Yasuhisa; Saga, Tsuneo

2014-04-01

(64)Cu-cyclam-RAFT-c(-RGDfK-)4, an αVβ3 integrin-targeting tetrameric cyclic RGD peptide probe, is a potential theranostic compound for positron emission tomography (PET) of tumor angiogenesis and for internal radiotherapy owing to the multiple decay modes of (64)Cu. Since kidneys are dose-limiting organs in internal radiotherapy, we aimed to reduce the renal accumulation of (64)Cu-cyclam-RAFT-c(-RGDfK-)4 by co-injection with Gelofusine (GF), a succinylated gelatin solution, and/or L-lysine (Lys), and to explore, for the first time, the related mechanisms using the noninvasive and quantitative PET imaging technology. Biodistribution assays, dynamic and static PET scans, and metabolism studies with radio-thin-layer chromatography (radio-TLC) were performed in healthy or αVβ3-positive tumor-bearing mice. In the results, co-injection with GF markedly reduced the renal uptake and slightly increased the tumor uptake of (64)Cu-cyclam-RAFT-c(-RGDfK-)4. L-Lysine alone had no effect on the probe biodistribution, but the combined use of Lys and GF tended to enhance the effect of GF. Dynamic PET and metabolite analysis by radio-TLC highly revealed that GF blocks the renal reabsorption of (64)Cu-cyclam-RAFT-c(-RGDfK-)4, but does not interfere with its metabolism and excretion. In conclusion, administration of GF and Lys is a useful strategy for kidney protection in (64)Cu-cyclam-RAFT-c(-RGDfK-)4-based internal radiotherapy. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

TU-AB-202-11: Tumor Segmentation by Fusion of Multi-Tracer PET Images Using Copula Based Statistical Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lapuyade-Lahorgue, J; Ruan, S; Li, H

Purpose: Multi-tracer PET imaging is getting more attention in radiotherapy by providing additional tumor volume information such as glucose and oxygenation. However, automatic PET-based tumor segmentation is still a very challenging problem. We propose a statistical fusion approach to joint segment the sub-area of tumors from the two tracers FDG and FMISO PET images. Methods: Non-standardized Gamma distributions are convenient to model intensity distributions in PET. As a serious correlation exists in multi-tracer PET images, we proposed a new fusion method based on copula which is capable to represent dependency between different tracers. The Hidden Markov Field (HMF) model ismore » used to represent spatial relationship between PET image voxels and statistical dynamics of intensities for each modality. Real PET images of five patients with FDG and FMISO are used to evaluate quantitatively and qualitatively our method. A comparison between individual and multi-tracer segmentations was conducted to show advantages of the proposed fusion method. Results: The segmentation results show that fusion with Gaussian copula can receive high Dice coefficient of 0.84 compared to that of 0.54 and 0.3 of monomodal segmentation results based on individual segmentation of FDG and FMISO PET images. In addition, high correlation coefficients (0.75 to 0.91) for the Gaussian copula for all five testing patients indicates the dependency between tumor regions in the multi-tracer PET images. Conclusion: This study shows that using multi-tracer PET imaging can efficiently improve the segmentation of tumor region where hypoxia and glucidic consumption are present at the same time. Introduction of copulas for modeling the dependency between two tracers can simultaneously take into account information from both tracers and deal with two pathological phenomena. Future work will be to consider other families of copula such as spherical and archimedian copulas, and to eliminate partial volume effect by considering dependency between neighboring voxels.« less

Evaluation of ECG-gated [(11)C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency.

PubMed

Hansson, Nils Henrik; Tolbod, Lars; Harms, Johannes; Wiggers, Henrik; Kim, Won Yong; Hansen, Esben; Zaremba, Tomas; Frøkiær, Jørgen; Jakobsen, Steen; Sørensen, Jens

2016-08-01

Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [(11)C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [(11)C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [(11)C]acetate PET. Thirty-five subjects with aortic valve stenosis underwent ECG-gated [(11)C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE. LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias -3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness. Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [(11)C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

PET/MR in oncology: an introduction with focus on MR and future perspectives for hybrid imaging

PubMed Central

Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin; Zamogilnaya, Yanna; Højgaard, Liselotte; Fischer, Barbara M

2012-01-01

After more than 20 years of research, a fully integrated PET/MR scanner was launched in 2010 enabling simultaneous acquisition of PET and MR imaging. Currently, no clinical indication for combined PET/MR has been established, however the expectations are high. In this paper we will discuss some of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number of different MRI techniques, such as DWI-MR (diffusion weighted imaging MR), DCE-MR (dynamic contrast enhanced MR), MRS (MR spectroscopy) and MR for attenuation correction of PET. All MR techniques presented in this paper have shown promising results in the treatment of patients with solid tumors and could be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new tracers and drugs will be discussed. PMID:23145362

Model-free quantification of dynamic PET data using nonparametric deconvolution

PubMed Central

Zanderigo, Francesca; Parsey, Ramin V; Todd Ogden, R

2015-01-01

Dynamic positron emission tomography (PET) data are usually quantified using compartment models (CMs) or derived graphical approaches. Often, however, CMs either do not properly describe the tracer kinetics, or are not identifiable, leading to nonphysiologic estimates of the tracer binding. The PET data are modeled as the convolution of the metabolite-corrected input function and the tracer impulse response function (IRF) in the tissue. Using nonparametric deconvolution methods, it is possible to obtain model-free estimates of the IRF, from which functionals related to tracer volume of distribution and binding may be computed, but this approach has rarely been applied in PET. Here, we apply nonparametric deconvolution using singular value decomposition to simulated and test–retest clinical PET data with four reversible tracers well characterized by CMs ([11C]CUMI-101, [11C]DASB, [11C]PE2I, and [11C]WAY-100635), and systematically compare reproducibility, reliability, and identifiability of various IRF-derived functionals with that of traditional CMs outcomes. Results show that nonparametric deconvolution, completely free of any model assumptions, allows for estimates of tracer volume of distribution and binding that are very close to the estimates obtained with CMs and, in some cases, show better test–retest performance than CMs outcomes. PMID:25873427

PET/MR Synchronization by Detection of Switching Gradients

NASA Astrophysics Data System (ADS)

Weissler, Bjoern; Gebhardt, Pierre; Lerche, Christoph W.; Soultanidis, Georgios M.; Wehner, Jakob; Heberling, Dirk; Schulz, Volkmar

2015-06-01

The full potential of simultaneous Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) acquisition, such as dynamic studies or motion compensation, can only be explored if the data of both modalities is temporally synchronized. As such hybrid imaging systems are commonly realized as custom-made PET inserts for commercially available MRI scanner, a synchronization solution has to be implemented (depending on the vendor of the MRI system). In contrast, we demonstrate a simple method for temporal synchronization, which does not require a connection to the MRI. It uses the normally undesired effect of induced voltages on the PET electronics from switching MRI gradients. The electronic circuit needs very few components and the gradient pick-up coils are made from PCB traces and vias on the PET detector boards. Neither programming the MRI nor any physical connection to the MR scanner is needed, thus avoiding electromagnetic compatibility problems. This method works inherently with most MRI sequences and is a vendor- independent solution. A characterization of the sensors in an MRI scanner showed that the MRI gradients are detected with a precision of 120 μs (with the current implementation). Using different trigger thresholds, it is possible to trigger selectively on certain MRI sequences, depending on their gradient slew rate settings. Timings and pulse diagrams of MRI sequences can be recognized from the generated data. The method was successfully used for temporal alignment between PET and MRI in an MRI-based PET-motion-compensation application.

Direct Estimation of Kinetic Parametric Images for Dynamic PET

PubMed Central

Wang, Guobao; Qi, Jinyi

2013-01-01

Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection data allows accurate noise modeling and has been shown to offer better image quality than conventional indirect methods, which reconstruct a sequence of PET images first and then perform tracer kinetic modeling pixel-by-pixel. Direct reconstruction of parametric images has gained increasing interests with the advances in computing hardware. Many direct reconstruction algorithms have been developed for different kinetic models. In this paper we review the recent progress in the development of direct reconstruction algorithms for parametric image estimation. Algorithms for linear and nonlinear kinetic models are described and their properties are discussed. PMID:24396500

Direct Parametric Image Reconstruction in Reduced Parameter Space for Rapid Multi-Tracer PET Imaging.

PubMed

Cheng, Xiaoyin; Li, Zhoulei; Liu, Zhen; Navab, Nassir; Huang, Sung-Cheng; Keller, Ulrich; Ziegler, Sibylle; Shi, Kuangyu

2015-02-12

The separation of multiple PET tracers within an overlapping scan based on intrinsic differences of tracer pharmacokinetics is challenging, due to limited signal-to-noise ratio (SNR) of PET measurements and high complexity of fitting models. In this study, we developed a direct parametric image reconstruction (DPIR) method for estimating kinetic parameters and recovering single tracer information from rapid multi-tracer PET measurements. This is achieved by integrating a multi-tracer model in a reduced parameter space (RPS) into dynamic image reconstruction. This new RPS model is reformulated from an existing multi-tracer model and contains fewer parameters for kinetic fitting. Ordered-subsets expectation-maximization (OSEM) was employed to approximate log-likelihood function with respect to kinetic parameters. To incorporate the multi-tracer model, an iterative weighted nonlinear least square (WNLS) method was employed. The proposed multi-tracer DPIR (MTDPIR) algorithm was evaluated on dual-tracer PET simulations ([18F]FDG and [11C]MET) as well as on preclinical PET measurements ([18F]FLT and [18F]FDG). The performance of the proposed algorithm was compared to the indirect parameter estimation method with the original dual-tracer model. The respective contributions of the RPS technique and the DPIR method to the performance of the new algorithm were analyzed in detail. For the preclinical evaluation, the tracer separation results were compared with single [18F]FDG scans of the same subjects measured 2 days before the dual-tracer scan. The results of the simulation and preclinical studies demonstrate that the proposed MT-DPIR method can improve the separation of multiple tracers for PET image quantification and kinetic parameter estimations.

Comparison of O-(2-18F-Fluoroethyl)-L-Tyrosine Positron Emission Tomography and Perfusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Patients with Progressive and Recurrent Glioma: A Hybrid Positron Emission Tomography/Magnetic Resonance Study.

PubMed

Verger, Antoine; Filss, Christian P; Lohmann, Philipp; Stoffels, Gabriele; Sabel, Michael; Wittsack, Hans-J; Kops, Elena Rota; Galldiks, Norbert; Fink, Gereon R; Shah, Nadim J; Langen, Karl-Josef

2018-05-01

To compare the diagnostic performance of O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) positron emission tomography (PET) and perfusion-weighted magnetic resonance imaging (PWI) for the diagnosis of progressive or recurrent glioma. Thirty-two pretreated gliomas (25 progressive or recurrent tumors, 7 treatment-related changes) were investigated with 18 F-FET PET and PWI via a hybrid PET/magnetic resonance scanner. Volumes of interest with a diameter of 16 mm were centered on the maximum of abnormality in the tumor area in PET and PWI maps (relative cerebral blood volume, relative cerebral blood flow, mean transit time) and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios as well as dynamic data for 18 F-FET uptake were calculated. Diagnostic accuracies were evaluated by receiver operating characteristic analyses, calculating the area under the curve. 18 F-FET PET showed a significant greater sensitivity to detect abnormalities in pretreated gliomas than PWI (76% vs. 52%, P = 0.03). The maximum tumor-to-brain ratio of 18 F-FET PET was the only parameter that discriminated treatment-related changes from progressive or recurrent gliomas (area under the curve, 0.78; P = 0.03, best cut-off 2.61; sensitivity 80%, specificity 86%, accuracy 81%). Among patients with signal abnormality in both modalities, 75% revealed spatially incongruent local hot spots. This pilot study suggests that 18 F-FET PET is superior to PWI to diagnose progressive or recurrent glioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Predicting tumor hypoxia in non-small cell lung cancer by combining CT, FDG PET and dynamic contrast-enhanced CT.

PubMed

Even, Aniek J G; Reymen, Bart; La Fontaine, Matthew D; Das, Marco; Jochems, Arthur; Mottaghy, Felix M; Belderbos, José S A; De Ruysscher, Dirk; Lambin, Philippe; van Elmpt, Wouter

2017-11-01

Most solid tumors contain inadequately oxygenated (i.e., hypoxic) regions, which tend to be more aggressive and treatment resistant. Hypoxia PET allows visualization of hypoxia and may enable treatment adaptation. However, hypoxia PET imaging is expensive, time-consuming and not widely available. We aimed to predict hypoxia levels in non-small cell lung cancer (NSCLC) using more easily available imaging modalities: FDG-PET/CT and dynamic contrast-enhanced CT (DCE-CT). For 34 NSCLC patients, included in two clinical trials, hypoxia HX4-PET/CT, planning FDG-PET/CT and DCE-CT scans were acquired before radiotherapy. Scans were non-rigidly registered to the planning CT. Tumor blood flow (BF) and blood volume (BV) were calculated by kinetic analysis of DCE-CT images. Within the gross tumor volume, independent clusters, i.e., supervoxels, were created based on FDG-PET/CT. For each supervoxel, tumor-to-background ratios (TBR) were calculated (median SUV/aorta SUV mean ) for HX4-PET/CT and supervoxel features (median, SD, entropy) for the other modalities. Two random forest models (cross-validated: 10 folds, five repeats) were trained to predict the hypoxia TBR; one based on CT, FDG, BF and BV, and one with only CT and FDG features. Patients were split in a training (trial NCT01024829) and independent test set (trial NCT01210378). For each patient, predicted, and observed hypoxic volumes (HV) (TBR > 1.2) were compared. Fifteen patients (3291 supervoxels) were used for training and 19 patients (1502 supervoxels) for testing. The model with all features (RMSE training: 0.19 ± 0.01, test: 0.27) outperformed the model with only CT and FDG-PET features (RMSE training: 0.20 ± 0.01, test: 0.29). All tumors of the test set were correctly classified as normoxic or hypoxic (HV > 1 cm 3 ) by the best performing model. We created a data-driven methodology to predict hypoxia levels and hypoxia spatial patterns using CT, FDG-PET and DCE-CT features in NSCLC. The model correctly classifies all tumors, and could therefore, aid tumor hypoxia classification and patient stratification.

Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 β-Amyloid Measures Across the Spectrum of Alzheimer Disease.

PubMed

Toledo, Jon B; Bjerke, Maria; Da, Xiao; Landau, Susan M; Foster, Norman L; Jagust, William; Jack, Clifford; Weiner, Michael; Davatzikos, Christos; Shaw, Leslie M; Trojanowski, John Q

2015-05-01

Cerebrospinal fluid (CSF) and positron emission tomographic (PET) amyloid biomarkers have been proposed for the detection of Alzheimer disease (AD) pathology in living patients and for the tracking of longitudinal changes, but the relation between biomarkers needs further study. To determine the association between CSF and PET amyloid biomarkers (cross-sectional and longitudinal measures) and compare the cutoffs for these measures. Longitudinal clinical cohort study from 2005 to 2014 including 820 participants with at least 1 florbetapir F-18 (hereafter referred to as simply florbetapir)-PET scan and at least 1 CSF β-amyloid 1-42 (Aβ1-42) sample obtained within 30 days of each other (501 participants had a second PET scan after 2 years, including 150 participants with CSF Aβ1-42 measurements). Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Four different PET scans processing pipelines from 2 different laboratories were compared. The PET cutoff values were established using a mixture-modeling approach, and different mathematical models were applied to define the association between CSF and PET amyloid measures. The values of the CSF Aβ1-42 samples and florbetapir-PET scans showed a nonlinear association (R2 = 0.48-0.66), with the strongest association for values in the middle range. The presence of a larger dynamic range of florbetapir-PET scan values in the higher range compared with the CSF Aβ1-42 plateau explained the differences in correlation with cognition (R2 = 0.36 and R2 = 0.25, respectively). The APOE genotype significantly modified the association between both biomarkers. The PET cutoff values derived from an unsupervised classifier converged with previous PET cutoff values and the established CSF Aβ1-42 cutoff levels. There was no association between longitudinal Aβ1-42 levels and standardized uptake value ratios during follow-up. The association between both biomarkers is limited to a middle range of values, is modified by the APOE genotype, and is absent for longitudinal changes; 4 different approaches in 2 different platforms converge on similar pathological Aβ cutoff levels; and different pipelines to process PET scans showed correlated but not identical results. Our findings suggest that both biomarkers measure different aspects of AD Aβ pathology.

Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?

PubMed

Cecchin, Diego; Palombit, Alessandro; Castellaro, Marco; Silvestri, Erica; Bui, Franco; Barthel, Henryk; Sabri, Osama; Corbetta, Maurizio; Bertoldo, Alessandra

2017-12-01

In the last 20 years growing attention has been devoted to multimodal imaging. The recent literature is rich of clinical and research studies that have been performed using different imaging modalities on both separate and integrated positron emission tomography (PET) and magnetic resonance (MR) scanners. However, today, hybrid PET/MR systems measure signals related to brain structure, metabolism, neurochemistry, perfusion, and neuronal activity simultaneously, i.e. in the same physiological conditions. A frequently raised question at meeting and symposia is: "Do we really need a hybrid PET/MR system? Are there any advantages over acquiring sequential and separate PET and MR scans?" The present paper is an attempt to answer these questions specifically in relation to PET combined with functional magnetic resonance imaging (fMRI) and arterial spin labeling. We searched (last update: June 2017) the databases PubMed, PMC, Google Scholar and Medline. We also included additional studies if they were cited in the selected articles. No language restriction was applied to the search, but the reviewed articles were all in English. Among all the retrieved articles, we selected only those performed using a hybrid PET/MR system. We found a total of 17 papers that were selected and discussed in three main groups according to the main radiopharmaceutical used: 18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and neuroreceptors (N.=6). Concerning studies using 18F-FDG, simultaneous PET/fMRI revealed that global aspects of functional organization (e.g. graph properties of functional connections) are partially associated with energy consumption. There are remarkable spatial and functional similarities across modalities, but also discrepant findings. More work is needed on this point. There are only a handful of papers comparing blood flow measurements with PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant regional CBF differences between these two modalities. However, at least in one study the correlation at the level of gray, white matter, and whole brain is rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that simultaneous PET/fMRI could be a useful tool to characterize functional connectivity along with dynamic neuroreceptor adaptation in several physiological (e.g. working memory) or pathological (e.g. pain) conditions, with or without drug administrations. The simultaneous acquisition of PET (using a number of radiotracers) and functional MRI (using a number of sequences) offers exciting opportunities that we are just beginning to explore. The results thus far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor adaptation, and network's energetic demand.

Pulmonary imaging using respiratory motion compensated simultaneous PET/MR

PubMed Central

Dutta, Joyita; Huang, Chuan; Li, Quanzheng; El Fakhri, Georges

2015-01-01

Purpose: Pulmonary positron emission tomography (PET) imaging is confounded by blurring artifacts caused by respiratory motion. These artifacts degrade both image quality and quantitative accuracy. In this paper, the authors present a complete data acquisition and processing framework for respiratory motion compensated image reconstruction (MCIR) using simultaneous whole body PET/magnetic resonance (MR) and validate it through simulation and clinical patient studies. Methods: The authors have developed an MCIR framework based on maximum a posteriori or MAP estimation. For fast acquisition of high quality 4D MR images, the authors developed a novel Golden-angle RAdial Navigated Gradient Echo (GRANGE) pulse sequence and used it in conjunction with sparsity-enforcing k-t FOCUSS reconstruction. The authors use a 1D slice-projection navigator signal encapsulated within this pulse sequence along with a histogram-based gate assignment technique to retrospectively sort the MR and PET data into individual gates. The authors compute deformation fields for each gate via nonrigid registration. The deformation fields are incorporated into the PET data model as well as utilized for generating dynamic attenuation maps. The framework was validated using simulation studies on the 4D XCAT phantom and three clinical patient studies that were performed on the Biograph mMR, a simultaneous whole body PET/MR scanner. Results: The authors compared MCIR (MC) results with ungated (UG) and one-gate (OG) reconstruction results. The XCAT study revealed contrast-to-noise ratio (CNR) improvements for MC relative to UG in the range of 21%–107% for 14 mm diameter lung lesions and 39%–120% for 10 mm diameter lung lesions. A strategy for regularization parameter selection was proposed, validated using XCAT simulations, and applied to the clinical studies. The authors’ results show that the MC image yields 19%–190% increase in the CNR of high-intensity features of interest affected by respiratory motion relative to UG and a 6%–51% increase relative to OG. Conclusions: Standalone MR is not the traditional choice for lung scans due to the low proton density, high magnetic susceptibility, and low T2∗ relaxation time in the lungs. By developing and validating this PET/MR pulmonary imaging framework, the authors show that simultaneous PET/MR, unique in its capability of combining structural information from MR with functional information from PET, shows promise in pulmonary imaging. PMID:26133621

Pulmonary imaging using respiratory motion compensated simultaneous PET/MR.

PubMed

Dutta, Joyita; Huang, Chuan; Li, Quanzheng; El Fakhri, Georges

2015-07-01

Pulmonary positron emission tomography (PET) imaging is confounded by blurring artifacts caused by respiratory motion. These artifacts degrade both image quality and quantitative accuracy. In this paper, the authors present a complete data acquisition and processing framework for respiratory motion compensated image reconstruction (MCIR) using simultaneous whole body PET/magnetic resonance (MR) and validate it through simulation and clinical patient studies. The authors have developed an MCIR framework based on maximum a posteriori or MAP estimation. For fast acquisition of high quality 4D MR images, the authors developed a novel Golden-angle RAdial Navigated Gradient Echo (GRANGE) pulse sequence and used it in conjunction with sparsity-enforcing k-t FOCUSS reconstruction. The authors use a 1D slice-projection navigator signal encapsulated within this pulse sequence along with a histogram-based gate assignment technique to retrospectively sort the MR and PET data into individual gates. The authors compute deformation fields for each gate via nonrigid registration. The deformation fields are incorporated into the PET data model as well as utilized for generating dynamic attenuation maps. The framework was validated using simulation studies on the 4D XCAT phantom and three clinical patient studies that were performed on the Biograph mMR, a simultaneous whole body PET/MR scanner. The authors compared MCIR (MC) results with ungated (UG) and one-gate (OG) reconstruction results. The XCAT study revealed contrast-to-noise ratio (CNR) improvements for MC relative to UG in the range of 21%-107% for 14 mm diameter lung lesions and 39%-120% for 10 mm diameter lung lesions. A strategy for regularization parameter selection was proposed, validated using XCAT simulations, and applied to the clinical studies. The authors' results show that the MC image yields 19%-190% increase in the CNR of high-intensity features of interest affected by respiratory motion relative to UG and a 6%-51% increase relative to OG. Standalone MR is not the traditional choice for lung scans due to the low proton density, high magnetic susceptibility, and low T2 (∗) relaxation time in the lungs. By developing and validating this PET/MR pulmonary imaging framework, the authors show that simultaneous PET/MR, unique in its capability of combining structural information from MR with functional information from PET, shows promise in pulmonary imaging.

Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography

PubMed Central

Chen, Haojun; Tong, Xiao; Lang, Lixin; Jacobson, Orit; Yung, Bryant C.; Yang, Xiangyu; Bai, Ruiliang; Kiesewetter, Dale O.; Ma, Ying; Wu, Hua; Niu, Gang; Chen, Xiaoyuan

2017-01-01

Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Pswere overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis. PMID:28744320

The effect of respiratory induced density variations on non-TOF PET quantitation in the lung.

PubMed

Holman, Beverley F; Cuplov, Vesna; Hutton, Brian F; Groves, Ashley M; Thielemans, Kris

2016-04-21

Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant (18)F-FDG and (18)F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung.

The effect of respiratory induced density variations on non-TOF PET quantitation in the lung

NASA Astrophysics Data System (ADS)

Holman, Beverley F.; Cuplov, Vesna; Hutton, Brian F.; Groves, Ashley M.; Thielemans, Kris

2016-04-01

Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant 18F-FDG and 18F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Carryn M., E-mail: carryn-anderson@uiowa.edu; Chang, Tangel; Graham, Michael M.

Purpose: To evaluate dynamic [{sup 18}F]-fluorodeoxyglucose (FDG) uptake methodology as a post–radiation therapy (RT) response assessment tool, potentially enabling accurate tumor and therapy-related inflammation differentiation, improving the posttherapy value of FDG–positron emission tomography/computed tomography (FDG-PET/CT). Methods and Materials: We prospectively enrolled head-and-neck squamous cell carcinoma patients who completed RT, with scheduled 3-month post-RT FDG-PET/CT. Patients underwent our standard whole-body PET/CT scan at 90 minutes, with the addition of head-and-neck PET/CT scans at 60 and 120 minutes. Maximum standardized uptake values (SUV{sub max}) of regions of interest were measured at 60, 90, and 120 minutes. The SUV{sub max} slope between 60 and 120 minutes and changemore » of SUV{sub max} slope before and after 90 minutes were calculated. Data were analyzed by primary site and nodal site disease status using the Cox regression model and Wilcoxon rank sum test. Outcomes were based on pathologic and clinical follow-up. Results: A total of 84 patients were enrolled, with 79 primary and 43 nodal evaluable sites. Twenty-eight sites were interpreted as positive or equivocal (18 primary, 8 nodal, 2 distant) on 3-month 90-minute FDG-PET/CT. Median follow-up was 13.3 months. All measured SUV endpoints predicted recurrence. Change of SUV{sub max} slope after 90 minutes more accurately identified nonrecurrence in positive or equivocal sites than our current standard of SUV{sub max} ≥2.5 (P=.02). Conclusions: The positive predictive value of post-RT FDG-PET/CT may significantly improve using novel second derivative analysis of dynamic triphasic FDG-PET/CT SUV{sub max} slope, accurately distinguishing tumor from inflammation on positive and equivocal scans.« less

Reproducibility and Accuracy of Quantitative Myocardial Blood Flow Using 82Rb-PET: Comparison with 13N-Ammonia

PubMed Central

Fakhri, Georges El

2011-01-01

82Rb cardiac PET allows the assessment of myocardial perfusion using a column generator in clinics that lack a cyclotron. We and others have previously shown that quantitation of myocardial blood flow (MBF) and coronary flow reserve (CFR) is feasible using dynamic 82Rb PET and factor and compartment analyses. The aim of the present work was to determine the intra- and inter-observer variability of MBF estimation using 82Rb PET as well as the reproducibility of our generalized factor + compartment analyses methodology to estimate MBF and assess its accuracy by comparing, in the same subjects, 82Rb estimates of MBF to those obtained using 13N-ammonia. Methods Twenty-two subjects were included in the reproducibility and twenty subjects in the validation study. Patients were injected with 60±5mCi of 82Rb and imaged dynamically for 6 minutes at rest and during dipyridamole stress Left and right ventricular (LV+RV) time-activity curves were estimated by GFADS and used as input to a 2-compartment kinetic analysis that estimates parametric maps of myocardial tissue extraction (K1) and egress (k2), as well as LV+RV contributions (fv,rv). Results Our results show excellent reproducibility of the quantitative dynamic approach itself with coefficients of repeatability of 1.7% for estimation of MBF at rest, 1.4% for MBF at peak stress and 2.8% for CFR estimation. The inter-observer reproducibility between the four observers that participated in this study was also very good with correlation coefficients greater than 0.87 between any two given observers when estimating coronary flow reserve. The reproducibility of MBF in repeated 82Rb studies was good at rest and excellent at peak stress (r2=0.835). Furthermore, the slope of the correlation line was very close to 1 when estimating stress MBF and CFR in repeated 82Rb studies. The correlation between myocardial flow estimates obtained at rest and during peak stress in 82Rb and 13N-ammonia studies was very good at rest (r2=0.843) and stress (r2=0.761). The Bland-Altman plots show no significant presence of proportional error at rest or stress, nor a dependence of the variations on the amplitude of the myocardial blood flow at rest or stress. A small systematic overestimation of 13N-ammonia MBF was observed with 82Rb at rest (0.129 ml/g/min) and the opposite, i.e., underestimation, at stress (0.22 ml/g/min). Conclusions Our results show that absolute quantitation of myocardial bloof flow is reproducible and accurate with 82Rb dynamic cardiac PET as compared to 13N-ammonia. The reproducibility of the quantitation approach itself was very good as well as inter-observer reproducibility. PMID:19525467

Static and dynamic (18) FDG-PET in normal hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Souza, Marcy J; Wall, Jonathan S; Stuckey, Alan; Daniel, Gregory B

2011-01-01

Positron emission tomography (PET) is often used to stage and monitor human cancer and has recently been used in a similar fashion in veterinary medicine. The most commonly used radiopharmaceutical is 2-Deoxy-2-[(18) F]-Fluoro-d-glucose ((18) F-FDG), which is concentrated and trapped within cells that use glucose as their energy substrate. We characterized the normal distribution of (18) F-FDG in 10 healthy Hispaniolan Amazon parrots (Amazona ventralis) by performing whole body PET scans at steady state, 60min after injection. Significant variability was found in the intestinal activity. Avian species are known to reflux fluid and electrolytes from their cloaca into their colon. To evaluate reflux as the cause of variability in intestinal distribution of (18) F-FDG, dynamic PET scans were performed on the coelomic cavity of six Hispaniolan Amazon parrots from time 0 to 60min postinjection of radiotracer. Reflux of radioactive material from the cloaca into the colon occurred in all birds to varying degrees and occurred before 60min. To evaluate the intestinal tract of clinical avian patients, dynamic scans must be performed starting immediately after injection so that increased radioactivity due to metabolism or hypermetabolic lesions such as cancer can be differentiated from increased radioactivity due to reflux of fluid from the cloaca. © 2010 Veterinary Radiology & Ultrasound.

Sex steroid hormones and brain function: PET imaging as a tool for research.

PubMed

Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

2018-02-01

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

In vivo biodistribution of ginkgolide B, a constituent of Ginkgo biloba, visualized by MicroPET.

PubMed

Suehiro, Makiko; Simpson, Norman R; Underwood, Mark D; Castrillon, John; Nakanishi, Koji; van Heertum, Ronald

2005-07-01

The in vivo dynamic behavior of ginkgolide B (GB), a terpene lactone constituent of the Ginkgo biloba extracts, in the living animal was visualized by positron emission tomographic (PET) imaging using a GB analogue labeled with the positron emitter (18)F. The in vivo imaging studies, combined with ex vivo dissection experiments, reveal that GB exists in 2 forms in the body: the original GB with its lactone rings closed and a second form with one of the rings open. The original GB in plasma is taken up rapidly by various organs including the liver, the intestine and possibly the stomach. Consequently, in plasma, the proportion of the ionized form of GB increases dramatically with time. Thereafter the ratio between the 2 forms appears to shift slowly towards equilibrium. The results suggest that more attention needs to be focused on in vivo dynamics between the 2 forms of GB.

Photoinduced Electron Transfer from Various Aniline Derivatives to Graphene Quantum Dots.

PubMed

Ghosh, Tufan; Chatterjee, Swarupa; Prasad, Edamana

2015-12-10

The present study utilizes the luminescence nature of the graphene quantum dots (GQDs) to analyze the mechanistic aspects of the photoinduced electron transfer (PET) processes between GQDs and aniline derivatives. A systematic investigation of PET from various aniline derivatives to GQDs has been presented. Solution-processable GQDs have been synthesized from graphene oxide (GO) at 200 °C. The as-synthesized GQDs exhibit a strong green luminescence at 510 nm, upon photoexcitation at 440 nm. Various aniline derivatives (aniline, N-methylaniline, N,N'-dimethylaniline, N-ethylaniline, N,N'-diethylaniline, and N,N'-diphenylaniline) have been utilized as electron donors to probe the PET process. Results from UV-visible absorption and steady-state and time-resolve luminescence spectroscopy suggest that the GQDs interact with the aniline derivatives in the excited state, which results in a significant luminescence quenching of the GQDs. The bimolecular rate constants of the dynamic quenching have been deduced for various donor-acceptor systems, and the values are in the range of (1.06-2.68) × 10(9) M(-1) s(-1). The negative values of the free energy change of the electron transfer process suggest that PET from aniline derivatives to GQDs is feasible and could be responsible for the luminescence quenching. The PET has been confirmed by detecting radical cations for certain aniline derivatives, using a nanosecond laser flash photolysis setup. The present study shows that among the various types of graphene systems, GQDs are better candidates for understanding the mechanism of PET in graphene-based donor-acceptor systems.

[18F]CFT [(18F)WIN 35,428], a radioligand to study the dopamine transporter with PET: characterization in human subjects.

PubMed

Laakso, A; Bergman, J; Haaparanta, M; Vilkman, H; Solin, O; Hietala, J

1998-03-01

We have characterized the usage of [18F]CFT (also known as [18F]WIN 35,428) as a radioligand for in vivo studies of human dopamine transporter by PET. CFT was labeled with 18F to a high specific activity, and dynamic PET scans were conducted in healthy volunteers at various time points up to 5 h from [18F]CFT injection. The regional distribution of [18F]CFT uptake correlated well with the known distribution of dopaminergic nerve terminals in the human brain and also with that of other dopamine transporter radioligands. Striatal binding peaked at 225 min after injection and declined thereafter, demonstrating the reversible nature of the binding to the dopamine transporter. Therefore, due to the relatively long half-life of 18F (109.8 min), PET scans with [18F]CFT could easily be conducted during the binding equilibrium, allowing estimation of Bmax/Kd values (i.e., binding potential). Binding potentials for putamen and caudate measured at equilibrium were 4.79+/-0.11 and 4.50+/-0.23, respectively. We were able to also visualize midbrain dopaminergic neurons (substantia nigra) with [18F]CFT in some subjects. In conclusion, the labeling of CFT with 18F allows PET scans to be conducted at binding equilibrium, and therefore a high signal-to-noise ratio and reliable quantification of binding potential can be achieved. With a high resolution 3D PET scanner, the quantification of extrastriatal dopamine transporters should become possible.

Mapping {sup 15}O Production Rate for Proton Therapy Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grogg, Kira; Alpert, Nathaniel M.; Zhu, Xuping

Purpose: This work was a proof-of-principle study for the evaluation of oxygen-15 ({sup 15}O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. Methods and Materials: Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of {sup 15}O production and clearance rates, which were compared to live versus dead rates formore » the rabbit and to Monte Carlo predictions. Results: PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of {sup 15}O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using {sup 15}O decay constant, whereas the live thigh activity decayed faster. Most importantly, the {sup 15}O production rates agreed within 2% (P>.5) between conditions. Conclusions: We developed a new method for quantitative measurement of {sup 15}O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of {sup 15}O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, {sup 15}O clearance rates may be useful in monitoring permeability changes due to therapy.« less

Optimization of Rb-82 PET acquisition and reconstruction protocols for myocardial perfusion defect detection

NASA Astrophysics Data System (ADS)

Tang, Jing; Rahmim, Arman; Lautamäki, Riikka; Lodge, Martin A.; Bengel, Frank M.; Tsui, Benjamin M. W.

2009-05-01

The purpose of this study is to optimize the dynamic Rb-82 cardiac PET acquisition and reconstruction protocols for maximum myocardial perfusion defect detection using realistic simulation data and task-based evaluation. Time activity curves (TACs) of different organs under both rest and stress conditions were extracted from dynamic Rb-82 PET images of five normal patients. Combined SimSET-GATE Monte Carlo simulation was used to generate nearly noise-free cardiac PET data from a time series of 3D NCAT phantoms with organ activities modeling different pre-scan delay times (PDTs) and total acquisition times (TATs). Poisson noise was added to the nearly noise-free projections and the OS-EM algorithm was applied to generate noisy reconstructed images. The channelized Hotelling observer (CHO) with 32× 32 spatial templates corresponding to four octave-wide frequency channels was used to evaluate the images. The area under the ROC curve (AUC) was calculated from the CHO rating data as an index for image quality in terms of myocardial perfusion defect detection. The 0.5 cycle cm-1 Butterworth post-filtering on OS-EM (with 21 subsets) reconstructed images generates the highest AUC values while those from iteration numbers 1 to 4 do not show different AUC values. The optimized PDTs for both rest and stress conditions are found to be close to the cross points of the left ventricular chamber and myocardium TACs, which may promote an individualized PDT for patient data processing and image reconstruction. Shortening the TATs for <~3 min from the clinically employed acquisition time does not affect the myocardial perfusion defect detection significantly for both rest and stress studies.

Joint penalized-likelihood reconstruction of time-activity curves and regions-of-interest from projection data in brain PET

NASA Astrophysics Data System (ADS)

Krestyannikov, E.; Tohka, J.; Ruotsalainen, U.

2008-06-01

This paper presents a novel statistical approach for joint estimation of regions-of-interest (ROIs) and the corresponding time-activity curves (TACs) from dynamic positron emission tomography (PET) brain projection data. It is based on optimizing the joint objective function that consists of a data log-likelihood term and two penalty terms reflecting the available a priori information about the human brain anatomy. The developed local optimization strategy iteratively updates both the ROI and TAC parameters and is guaranteed to monotonically increase the objective function. The quantitative evaluation of the algorithm is performed with numerically and Monte Carlo-simulated dynamic PET brain data of the 11C-Raclopride and 18F-FDG tracers. The results demonstrate that the method outperforms the existing sequential ROI quantification approaches in terms of accuracy, and can noticeably reduce the errors in TACs arising due to the finite spatial resolution and ROI delineation.

The dynamics of Alzheimer's disease biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort.

PubMed

Caroli, A; Frisoni, G B

2010-08-01

The aim of this study was to investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Abeta 1-42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD. Two hundred twenty-nine cognitively healthy subjects, 154 mild cognitive impairment (MCI) patients converted to AD, and 193 (95 early and 98 late) AD patients were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For each biomarker, individual values were Z-transformed and plotted against ADAS-cog scores, and sigmoid and linear fits were compared. For most biomarkers the sigmoid model fitted data significantly better than the linear model. Abeta 1-42 time course followed a steep curve, stabilizing early in the disease course. CSF tau and hippocampal volume changed later showing similar monotonous trends, reflecting disease progression. Hippocampal loss trend was steeper and occurred earlier in time in APOE epsilon4 carriers than in non-carriers. FDG-PET started changing early in time and likely followed a linear decline. In conclusion, this study provides the first evidence in favor of the dynamic biomarker model which has recently been proposed. 2010 Elsevier Inc. All rights reserved.

WE-H-207A-05: Spatial Co-Localization of F-18 NaF Vs. F-18 FDG Defined Disease Volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferjancic, P; Harmon, S; Jeraj, R

Purpose: Both [F-18]NaF and [F-18]FDG show promise for quantitative PET/CT assessment in metastatic prostate cancer to bone. Broad agreement between the tracers has been shown but voxel-wise correspondence has not been explored in depth. This study evaluates the spatial co-localization of [F-18]NaF PET and [F-18]FDG PET in bone lesions. Methods: Seventy-three lesion contours were identified in six patients receiving dynamic NaF PET/CT and FDG PET/CT scans two hours apart using identical fields-of-view. Tracer uptake (SUV) reflecting 60 minutes post-injection was modeled from kinetic parameters. Lesions were segmented by a physician separately on NaF PET and FDG PET. PET images weremore » rigidly aligned using skeletal references on CT images. Lesion size, degree of overlap, voxel-wise tracer uptake values (SUV), and CT density distributions were compared using Dice coefficient, Positive Predictive Value (PPV), and Spearman rank correlation tests. Results: Across all patients, 42 lesions were identified on NaF PET (median 1.4 cm{sup 3}, range <1–204 cm{sup 3}) compared to 31 using FDG PET (median 1.8 cm{sup 3}, range <1–244 cm{sup 3}). Spatial cooccurrence was found in 25 lesion pairs. Lesions on NaF PET had PPV of 0.91 and on FDG a PPV of 0.65. Overall, NaF-defined lesions were 47% (±24%) larger by volume with moderate overlap to FDG, resulting in mean Dice coefficient of 34% (±22%). In areas of overlap, voxel-wise correlation of NaF and FDG SUV was moderate (ρ=0.56). Expanding to regions of non-spatial overlap, voxels contained in FDG-only contours were almost exclusively low HU (median 118), compared to dense regions of NaF-only voxels (median 250). In sclerotic sub-volumes (HU > 300) NaF-defined contours encompassed 83% of total FDG volume. Conclusion: Moderate voxel-wise correlation of FDG and NaF PET/CT uptake was observed. Spatial discrepancies in FDG and NaF PET/CT imaging of boney metastases could be influenced by poor sensitivity of FDG PET/CT in sclerotic regions. Funded by Prostate Cancer Foundation.« less

Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

PubMed

Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

2013-06-01

In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study provided proof of principle that our simplified ED (18)F-FDG PET/CT protocol includes endpoints that effectively detect HCC hypervascularization; this finding suggests that the protocol can be used routinely.

Iodine-122-labeled amphetamine derivative with potential for PET brain blood-flow studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathis, C.A.; Sargent, T. 3d.; Shulgin, A.T.

1985-11-01

The positron emitter SSI (t1/2 3.6 min) was collected from a xenon- SS/iodine- SS ( SSXe/ SSI) generator and incorporated into an amphetamine analog, 2,4-dimethoxy-N,N-dimethyl-5-( SSI)iodophenylisopropylamine (5-( SSI)-2,4-DNNA). The remote synthesis was achieved in 3 min with a 50% radioincorporation yield and a product radiopurity of greater than 98%. 5-( SSI)-2,4-DNNA was injected into a beagle dog and a brain section imaged with positron emission tomography (PET). The uptake and retention of 5-( SSI)-2,4-DNNA was compared to that of YSRb in the same animal. Dynamic PET activity data were obtained 0-20 min postinjection of 5-( SSI)-2,4-DNNA and showed rapid uptakemore » by brain and good cerebral/extracerebral tissue distinction. A whole-body scan of a dog was also obtained with 5-123I-2,4-DNNA showing uptake in brain, lung, and other body organs. The feasibility of incorporating SSI into an extracted brain perfusion agent for use with PET is demonstrated.« less

Ultrafast photoinduced electron transfer in the micelle and the gel phase of a PEO-PPO-PEO triblock copolymer

NASA Astrophysics Data System (ADS)

Mandal, Ujjwal; Ghosh, Subhadip; Dey, Shantanu; Adhikari, Aniruddha; Bhattacharyya, Kankan

2008-04-01

Ultrafast photoinduced electron transfer (PET) from N,N-dimethylaniline (DMA) to coumarin dyes is studied in the micelle and the gel phase of a triblock copolymer, (PEO)20-(PPO)70-(PEO)20 (Pluronic P123) by picosecond and femtosecond emission spectroscopies. The rate of PET in a P123 micelle and gel is found to be nonexponential and faster than the slow components of solvation dynamics. In a P123 micelle and gel, PET occurs on multiple time scales ranging from a subpicosecond time scale to a few nanoseconds. In the gel phase, the highest rate constant (9.3×109M-1s-1) of ET for C152 is about two times higher than that (3.8×109M-1s-1) observed in micelle phase. The ultrafast components of electron transfer (ET) exhibits a bell shaped dependence with the free energy change which is similar to the Marcus inversion. Possible reasons for slower PET in P123 micelle compared to other micelles and relative to P123 gel are discussed.

Automatic delineation of brain regions on MRI and PET images from the pig.

PubMed

Villadsen, Jonas; Hansen, Hanne D; Jørgensen, Louise M; Keller, Sune H; Andersen, Flemming L; Petersen, Ida N; Knudsen, Gitte M; Svarer, Claus

2018-01-15

The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated. Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake. A parcellated PET template that allows for automatic spatial normalization to PET images of any radiotracer. MRI and [ 11 C]Cimbi-36 PET scans obtained in sixteen pigs made the basis for the atlas. The high resolution MRI scans allowed for creation of an accurately averaged MRI template. By aligning the within-subject PET scans to their MRI counterparts, an averaged PET template was created in the same space. We developed an automatic procedure for spatial normalization of the averaged PET template to new PET images and hereby facilitated transfer of the atlas regional parcellation. Evaluation of the automatic spatial normalization procedure found the median voxel displacement to be 0.22±0.08mm using the MRI template with individual MRI images and 0.92±0.26mm using the PET template with individual [ 11 C]Cimbi-36 PET images. We tested the automatic procedure by assessing eleven PET radiotracers with different kinetics and spatial distributions by using perfusion-weighted images of early PET time frames. We here present an automatic procedure for accurate and reproducible spatial normalization and parcellation of pig PET images of any radiotracer with reasonable blood-brain barrier penetration. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetic Modeling of PET Data Without Blood Sampling

NASA Astrophysics Data System (ADS)

Bentourkia, M.

2005-06-01

In positron emission tomography (PET) imaging, application of kinetic modeling always requires an input curve (IC) together with the PET data. The IC can be obtained by means of external blood sampling or, in the case of cardiac studies, by means of a region-of-interest (ROI) drawn on the blood pool. It is, however, very unsuitable to withdraw and to analyze blood samples, and in small animals, these operations become difficult, while ICs determined from ROIs are generally contaminated by emissions from neighboring sites, or they are underestimated because of partial volume effect. In this paper, we report a new method to extract kinetic parameters from dynamic PET studies without a priori knowledge of the IC. The method is applied in human brain data measured with fluorodeoxyglucose (FDG) human-brain and in cardiac-rat perfusion studies with /sup 13/N-ammonia and /sup 11/C-acetate. The tissue blood volume (TBV), usually fitted together with the rate constants, is extracted simultaneously with the tissue time activity curves for cardiac studies, while for brain gray matter, TBV is known to be about 4% to 7%. The shape of IC is obtained by means of factor analysis from an ROI drawn around a cardiac tissue or a brain artery. The results show a good correlation (p<0.05) between the cerebral metabolic rate of glucose, myocardial blood flow, and oxygen consumption obtained with the new method in comparison to the usual method. In conclusion, it is possible to apply kinetic modeling without any blood sampling, which significantly simplifies PET acquisition and data analysis.

Parallel image reconstruction for 3D positron emission tomography from incomplete 2D projection data

NASA Astrophysics Data System (ADS)

Guerrero, Thomas M.; Ricci, Anthony R.; Dahlbom, Magnus; Cherry, Simon R.; Hoffman, Edward T.

1993-07-01

The problem of excessive computational time in 3D Positron Emission Tomography (3D PET) reconstruction is defined, and we present an approach for solving this problem through the construction of an inexpensive parallel processing system and the adoption of the FAVOR algorithm. Currently, the 3D reconstruction of the 610 images of a total body procedure would require 80 hours and the 3D reconstruction of the 620 images of a dynamic study would require 110 hours. An inexpensive parallel processing system for 3D PET reconstruction is constructed from the integration of board level products from multiple vendors. The system achieves its computational performance through the use of 6U VME four i860 processor boards, the processor boards from five manufacturers are discussed from our perspective. The new 3D PET reconstruction algorithm FAVOR, FAst VOlume Reconstructor, that promises a substantial speed improvement is adopted. Preliminary results from parallelizing FAVOR are utilized in formulating architectural improvements for this problem. In summary, we are addressing the problem of excessive computational time in 3D PET image reconstruction, through the construction of an inexpensive parallel processing system and the parallelization of a 3D reconstruction algorithm that uses the incomplete data set that is produced by current PET systems.

An assessment of the impact of the pet trade on five CITES-Appendix II case studies - Boa constrictor imperator

USGS Publications Warehouse

Montgomery, Chad E.; Boback, Scott M.; Reed, Robert N.; Frazier, Julius A.

2015-01-01

Boa constrictor is a wide ranging snake species that is common in the pet trade and is currently listed in CITES Appendix II. Hog Island boas, or Cayos Cochinos boas, are a dwarf, insular race of Boa constrictor imperator endemic to the Cayos Cochinos Archipelago, Honduras. Cayos Cochinos boas are prized in the international pet trade for their light pink dorsal coloration, as well as for being much smaller and more docile than mainland boas (Porras, 1999; Russo, 2007). The boa population in the Cayos Cochinos was heavily exploited for the pet trade from 1979 to 1993, and researchers reported finding no boas on the islands during a five day herpetological survey trip in the early 1990s (Wilson and CruzDiaz, 1993), leading to the speculation that the population had been extirpated (e.g., Russo, 2007). The Cayos Cochinos Archipelago Natural Marine Monument has been managed by the Honduran Coral Reef Foundation since 1994 and prohibits removal of boas from the area. Poaching for the pet trade continues today, although at a lower level. Due to the endemic nature of this island morph of B. c. imperator it is imperative that we understand the dynamics of the populations and the ongoing threats that could negatively impact their long-term survival.

Vision 20/20: Simultaneous CT-MRI — Next chapter of multimodality imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ge, E-mail: wangg6@rpi.edu; Xi, Yan; Gjesteby, Lars

Multimodality imaging systems such as positron emission tomography-computed tomography (PET-CT) and MRI-PET are widely available, but a simultaneous CT-MRI instrument has not been developed. Synergies between independent modalities, e.g., CT, MRI, and PET/SPECT can be realized with image registration, but such postprocessing suffers from registration errors that can be avoided with synchronized data acquisition. The clinical potential of simultaneous CT-MRI is significant, especially in cardiovascular and oncologic applications where studies of the vulnerable plaque, response to cancer therapy, and kinetic and dynamic mechanisms of targeted agents are limited by current imaging technologies. The rationale, feasibility, and realization of simultaneous CT-MRImore » are described in this perspective paper. The enabling technologies include interior tomography, unique gantry designs, open magnet and RF sequences, and source and detector adaptation. Based on the experience with PET-CT, PET-MRI, and MRI-LINAC instrumentation where hardware innovation and performance optimization were instrumental to construct commercial systems, the authors provide top-level concepts for simultaneous CT-MRI to meet clinical requirements and new challenges. Simultaneous CT-MRI fills a major gap of modality coupling and represents a key step toward the so-called “omnitomography” defined as the integration of all relevant imaging modalities for systems biology and precision medicine.« less

Spatiotemporal analysis of tumor uptake patterns in dynamic (18)FDG-PET and dynamic contrast enhanced CT.

PubMed

Malinen, Eirik; Rødal, Jan; Knudtsen, Ingerid Skjei; Søvik, Åste; Skogmo, Hege Kippenes

2011-08-01

Molecular and functional imaging techniques such as dynamic positron emission tomography (DPET) and dynamic contrast enhanced computed tomography (DCECT) may provide improved characterization of tumors compared to conventional anatomic imaging. The purpose of the current work was to compare spatiotemporal uptake patterns in DPET and DCECT images. A PET/CT protocol comprising DCECT with an iodine based contrast agent and DPET with (18)F-fluorodeoxyglucose was set up. The imaging protocol was used for examination of three dogs with spontaneous tumors of the head and neck at sessions prior to and after fractionated radiotherapy. Software tools were developed for downsampling the DCECT image series to the PET image dimensions, for segmentation of tracer uptake pattern in the tumors and for spatiotemporal correlation analysis of DCECT and DPET images. DCECT images evaluated one minute post injection qualitatively resembled the DPET images at most imaging sessions. Segmentation by region growing gave similar tumor extensions in DCECT and DPET images, with a median Dice similarity coefficient of 0.81. A relatively high correlation (median 0.85) was found between temporal tumor uptake patterns from DPET and DCECT. The heterogeneity in tumor uptake was not significantly different in the DPET and DCECT images. The median of the spatial correlation was 0.72. DCECT and DPET gave similar temporal wash-in characteristics, and the images also showed a relatively high spatial correlation. Hence, if the limited spatial resolution of DPET is considered adequate, a single DPET scan only for assessing both tumor perfusion and metabolic activity may be considered. However, further work on a larger number of cases is needed to verify the correlations observed in the present study.

Dynamic Contrast-Enhanced Perfusion Area-Detector CT: Preliminary Comparison of Diagnostic Performance for N Stage Assessment With FDG PET/CT in Non-Small Cell Lung Cancer.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Sugihara, Naoki; Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Yoshikawa, Takeshi

2017-11-01

The objective of our study was to directly compare the capability of dynamic first-pass contrast-enhanced (CE) perfusion area-detector CT (ADCT) and FDG PET/CT for differentiation of metastatic from nonmetastatic lymph nodes and assessment of N stage in patients with non-small cell lung carcinoma (NSCLC). Seventy-seven consecutive patients, 45 men (mean age ± SD, 70.4 ± 5.9 years) and 32 women (71.2 ± 7.7 years), underwent dynamic first-pass CE-perfusion ADCT at two or three different positions for covering the entire thorax, FDG PET/CT, surgical treatment, and pathologic examination. From all ADCT data for each of the subjects, a whole-chest perfusion map was computationally generated using the dual- and single-input maximum slope and Patlak plot methods. For quantitative N stage assessment, perfusion parameters and the maximum standardized uptake value (SUV max ) for each lymph node were determined by measuring the relevant ROI. ROC curve analyses were performed for comparing the diagnostic capability of each of the methods on a per-node basis. N stages evaluated by each of the indexes were then statistically compared with the final pathologic diagnosis by means of chi-square and kappa statistics. The area under the ROC curve (A z ) values of systemic arterial perfusion (A z = 0.89), permeability surface (A z = 0.78), and SUV max (A z = 0.85) were significantly larger than the A z values of total perfusion (A z = 0.70, p < 0.05) and distribution volume (A z = 0.55, p < 0.05). For each of the threshold values, agreement for systemic arterial perfusion calculated using the dual-input maximum slope model was substantial (κ = 0.70, p < 0.0001), and agreement for SUV max was moderate (κ = 0.60, p < 0.0001). Dynamic first-pass CE-perfusion ADCT is as useful as FDG PET/CT for the differentiation of metastatic from nonmetastatic lymph nodes and assessment of N stage in patients with NSCLC.

Ultraviolet photodissociation dynamics of the benzyl radical.

PubMed

Song, Yu; Zheng, Xianfeng; Lucas, Michael; Zhang, Jingsong

2011-05-14

Ultraviolet (UV) photodissociation dynamics of jet-cooled benzyl radical via the 4(2)B(2) electronically excited state is studied in the photolysis wavelength region of 228 to 270 nm using high-n Rydberg atom time-of-flight (HRTOF) and resonance enhanced multiphoton ionization (REMPI) techniques. In this wavelength region, H-atom photofragment yield (PFY) spectra are obtained using ethylbenzene and benzyl chloride as the precursors of benzyl radical, and they have a broad peak centered around 254 nm and are in a good agreement with the previous UV absorption spectra of benzyl. The H + C(7)H(6) product translational energy distributions, P(E(T))s, are derived from the H-atom TOF spectra. The P(E(T)) distributions peak near 5.5 kcal mol(-1), and the fraction of average translational energy in the total excess energy, , is ∼0.3. The P(E(T))s indicate the production of fulvenallene + H, which was suggested by recent theoretical studies. The H-atom product angular distribution is isotropic, with the anisotropy parameter β ≈ 0. The H/D product ratios from isotope labeling studies using C(6)H(5)CD(2) and C(6)D(5)CH(2) are reasonably close to the statistical H/D ratios, suggesting that the H/D atoms are scrambled in the photodissociation of benzyl. The dissociation mechanism is consistent with internal conversion of the electronically excited benzyl followed by unimolecular decomposition of the hot benzyl radical on the ground state.

FDG-Avid Portal Vein Tumor Thrombosis from Hepatocellular Carcinoma in Contrast-Enhanced FDG PET/CT

PubMed Central

Nguyen, Xuan Canh; Nguyen, Dinh Song Huy; Ngo, Van Tan; Maurea, Simone

2015-01-01

Objective(s): In this study, we aimed to describe the characteristics of portal vein tumor thrombosis (PVTT), complicating hepatocellular carcinoma (HCC) in contrast-enhanced FDG PET/CT scan. Methods: In this retrospective study, 9 HCC patients with FDG-avid PVTT were diagnosed by contrast-enhanced fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), which is a combination of dynamic liver CT scan, multiphase imaging, and whole-body PET scan. PET and CT DICOM images of patients were imported into the PET/CT imaging system for the re-analysis of contrast enhancement and FDG uptake in thrombus, the diameter of the involved portal vein, and characteristics of liver tumors and metastasis. Results: Two patients with previously untreated HCC and 7 cases with previously treated HCC had FDG-avid PVTT in contrast-enhanced FDG PET/CT scan. During the arterial phase of CT scan, portal vein thrombus showed contrast enhancement in 8 out of 9 patients (88.9%). PET scan showed an increased linear FDG uptake along the thrombosed portal vein in all patients. The mean greatest diameter of thrombosed portal veins was 1.8 ± 0.2 cm, which was significantly greater than that observed in normal portal veins (P<0.001). FDG uptake level in portal vein thrombus was significantly higher than that of blood pool in the reference normal portal vein (P=0.001). PVTT was caused by the direct extension of liver tumors. All patients had visible FDG-avid liver tumors in contrast-enhanced images. Five out of 9 patients (55.6%) had no extrahepatic metastasis, 3 cases (33.3%) had metastasis of regional lymph nodes, and 1 case (11.1%) presented with distant metastasis. The median estimated survival time of patients was 5 months. Conclusion: The intraluminal filling defect consistent with thrombous within the portal vein, expansion of the involved portal vein, contrast enhancement, and linear increased FDG uptake of the thrombus extended from liver tumor are findings of FDG-avid PVTT from HCC in contrast-enhanced FDG PET/CT. PMID:27408876

IMPROVED DERIVATION OF INPUT FUNCTION IN DYNAMIC MOUSE [18F]FDG PET USING BLADDER RADIOACTIVITY KINETICS

PubMed Central

Wong, Koon-Pong; Zhang, Xiaoli; Huang, Sung-Cheng

2013-01-01

Purpose Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. Methods Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. Total accumulated radioactivity in the urinary bladder was fitted to a renal compartmental model with the last blood sample and a 1-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of 4-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0–1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects and erythrocytes uptake) and the late-time blood estimates. Using only the blood sample acquired at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. Results The area under the plasma TACs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal muscle and liver computed by the Patlak analysis using estimated and measured plasma TACs were in excellent agreement (slope ~ 1; R2 > 0.938). The IF estimated using only the last blood sample acquired at the end of the study and the use of liver TAC as plasma IF provided less reliable results. Conclusions The estimated plasma IFs obtained with the hybrid model agreed well with those derived from arterial blood sampling. Importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated dynamic [18F]FDG PET studies on the same animal. Liver TAC is unsuitable as an input function for absolute quantification of [18F]FDG PET data. PMID:23322346

Model-independent plot of dynamic PET data facilitates data interpretation and model selection.

PubMed

Munk, Ole Lajord

2012-02-21

When testing new PET radiotracers or new applications of existing tracers, the blood-tissue exchange and the metabolism need to be examined. However, conventional plots of measured time-activity curves from dynamic PET do not reveal the inherent kinetic information. A novel model-independent volume-influx plot (vi-plot) was developed and validated. The new vi-plot shows the time course of the instantaneous distribution volume and the instantaneous influx rate. The vi-plot visualises physiological information that facilitates model selection and it reveals when a quasi-steady state is reached, which is a prerequisite for the use of the graphical analyses by Logan and Gjedde-Patlak. Both axes of the vi-plot have direct physiological interpretation, and the plot shows kinetic parameter in close agreement with estimates obtained by non-linear kinetic modelling. The vi-plot is equally useful for analyses of PET data based on a plasma input function or a reference region input function. The vi-plot is a model-independent and informative plot for data exploration that facilitates the selection of an appropriate method for data analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

PubMed Central

Corcoran, Andrea E.; Brust, Rachael D.; Chang, YoonJeung; Nattie, Eugene E.

2017-01-01

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 (Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO2. Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. PMID:28073937

Whole-body PET parametric imaging employing direct 4D nested reconstruction and a generalized non-linear Patlak model

NASA Astrophysics Data System (ADS)

Karakatsanis, Nicolas A.; Rahmim, Arman

2014-03-01

Graphical analysis is employed in the research setting to provide quantitative estimation of PET tracer kinetics from dynamic images at a single bed. Recently, we proposed a multi-bed dynamic acquisition framework enabling clinically feasible whole-body parametric PET imaging by employing post-reconstruction parameter estimation. In addition, by incorporating linear Patlak modeling within the system matrix, we enabled direct 4D reconstruction in order to effectively circumvent noise amplification in dynamic whole-body imaging. However, direct 4D Patlak reconstruction exhibits a relatively slow convergence due to the presence of non-sparse spatial correlations in temporal kinetic analysis. In addition, the standard Patlak model does not account for reversible uptake, thus underestimating the influx rate Ki. We have developed a novel whole-body PET parametric reconstruction framework in the STIR platform, a widely employed open-source reconstruction toolkit, a) enabling accelerated convergence of direct 4D multi-bed reconstruction, by employing a nested algorithm to decouple the temporal parameter estimation from the spatial image update process, and b) enhancing the quantitative performance particularly in regions with reversible uptake, by pursuing a non-linear generalized Patlak 4D nested reconstruction algorithm. A set of published kinetic parameters and the XCAT phantom were employed for the simulation of dynamic multi-bed acquisitions. Quantitative analysis on the Ki images demonstrated considerable acceleration in the convergence of the nested 4D whole-body Patlak algorithm. In addition, our simulated and patient whole-body data in the postreconstruction domain indicated the quantitative benefits of our extended generalized Patlak 4D nested reconstruction for tumor diagnosis and treatment response monitoring.

Nonlinear Association Between Cerebrospinal Fluid and Florbetapir F-18 β-Amyloid Measures Across the Spectrum of Alzheimer Disease

PubMed Central

Toledo, Jon B.; Bjerke, Maria; Da, Xiao; Landau, Susan M.; Foster, Norman L; Jagust, William; Jack, Clifford; Weiner, Michael; Davatzikos, Christos; Shaw, Leslie M.; Trojanowski, John Q.

2017-01-01

IMPORTANCE Cerebrospinal fluid (CSF) and positron emission tomographic (PET) amyloid biomarkers have been proposed for the detection of Alzheimer disease (AD) pathology in living patients and for the tracking of longitudinal changes, but the relation between biomarkers needs further study. OBJECTIVE To determine the association between CSF and PET amyloid biomarkers (cross-sectional and longitudinal measures) and compare the cutoffs for these measures. DESIGN, SETTING, AND PARTICIPANTS Longitudinal clinical cohort study from 2005 to 2014 including 820 participants with at least 1 florbetapir F-18 (hereafter referred to as simply florbetapir)–PET scan and at least 1 CSF β-amyloid 1–42 (Aβ1–42) sample obtained within 30 days of each other (501 participants had a second PET scan after 2 years, including 150 participants with CSF Aβ1–42 measurements). Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative database. MAIN OUTCOMES AND MEASURES Four different PET scans processing pipelines from 2 different laboratories were compared. The PET cutoff values were established using a mixture-modeling approach, and different mathematical models were applied to define the association between CSF and PET amyloid measures. RESULTS The values of the CSF Aβ1–42 samples and florbetapir-PET scans showed a nonlinear association (R2 = 0.48–0.66), with the strongest association for values in the middle range. The presence of a larger dynamic range of florbetapir-PET scan values in the higher range compared with the CSF Aβ1–42 plateau explained the differences in correlation with cognition (R2 = 0.36 and R2 = 0.25, respectively). The APOE genotype significantly modified the association between both biomarkers. The PET cutoff values derived from an unsupervised classifier converged with previous PET cutoff values and the established CSF Aβ1–42 cutoff levels. There was no association between longitudinal Aβ1–42 levels and standardized uptake value ratios during follow-up. CONCLUSIONS AND RELEVANCE The association between both biomarkers is limited to a middle range of values, is modified by the APOE genotype, and is absent for longitudinal changes; 4 different approaches in 2 different platforms converge on similar pathological Aβ cutoff levels; and different pipelines to process PET scans showed correlated but not identical results. Our findings suggest that both biomarkers measure different aspects of AD Aβ pathology. PMID:25822737

68Ga-EDTA PET/CT imaging and plasma clearance for glomerular filtration rate quantification: comparison to conventional 51Cr-EDTA.

PubMed

Hofman, Michael; Binns, David; Johnston, Val; Siva, Shankar; Thompson, Mick; Eu, Peter; Collins, Marnie; Hicks, Rodney J

2015-03-01

Glomerular filtration rate (GFR) can accurately be determined using (51)Cr-ethylenediaminetetraacetic acid (EDTA) plasma clearance counting but is time-consuming and requires technical skills and equipment not always available in imaging departments. (68)Ga-EDTA can be readily available using an onsite generator, and PET/CT enables both imaging of renal function and accurate camera-based quantitation of clearance of activity from blood and its appearance in the urine. This study aimed to assess agreement between (68)Ga-EDTA GFR ((68)Ga-GFR) and (51)Cr-EDTA GFR ((51)Cr-GFR), using serial plasma sampling and PET imaging. (68)Ga-EDTA and (51)Cr-EDTA were injected concurrently in 31 patients. Dynamic PET/CT encompassing the kidneys was acquired for 10 min followed by 3 sequential 3-min multibed step acquisitions from kidneys to bladder. PET quantification was performed using renal activity at 1-2 min (PETinitial), renal excretion at 2-10 min (PETearly), and, subsequently, urinary excretion into the collecting system and bladder (PETlate). Plasma sampling at 2, 3, and 4 h was performed, with (68)Ga followed by (51)Cr counting after positron decay. The level of agreement for GFR determination was calculated using a Bland-Altman plot and Pearson correlation coefficient (PCC). (51)Cr-GFR ranged from 10 to 220 mL/min (mean, 85 mL/min). There was good agreement between (68)Ga-GFR and (51)Cr-GFR using serial plasma sampling, with a Bland-Altman bias of -14 ± 20 mL/min and a PCC of 0.94 (95% confidence interval, 0.88-0.97). Of the 3 methods used for camera-based quantification, the strongest correlation was for plasma sampling-derived GFR with PETlate (PCC of 0.90; 95% confidence interval, 0.80-0.95). (68)Ga-GFR agreed well with (51)Cr-GFR for estimation of GFR using serial plasma counting. PET dynamic imaging provides a method to estimate GFR without plasma sampling, with the additional advantage of enabling renal imaging in a single study. Additional validation in a larger cohort is warranted to further assess utility. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Whole-tumor histogram analysis of the cerebral blood volume map: tumor volume defined by 11C-methionine positron emission tomography image improves the diagnostic accuracy of cerebral glioma grading.

PubMed

Wu, Rongli; Watanabe, Yoshiyuki; Arisawa, Atsuko; Takahashi, Hiroto; Tanaka, Hisashi; Fujimoto, Yasunori; Watabe, Tadashi; Isohashi, Kayako; Hatazawa, Jun; Tomiyama, Noriyuki

2017-10-01

This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

Pharmacokinetic Analysis of Dynamic 18F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer.

PubMed

Schwartz, Jazmin; Grkovski, Milan; Rimner, Andreas; Schöder, Heiko; Zanzonico, Pat B; Carlin, Sean D; Staton, Kevin D; Humm, John L; Nehmeh, Sadek A

2017-06-01

Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. 18 F-fluoromisonidazole ( 18 F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of 18 F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Methods: Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static 18 F-FDG and a dynamic 18 F-FMISO scan lasting 168 ± 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered 18 F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. Results: We derived average values of 18 F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate ( k 3 ) and delivery rate ( K 1 ), influx rate ( K i ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, k 3 and K i had a significant strong correlation for all tissue types. The TBR- k 3 correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, K 1 - k 3 voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R = -0.23 ± 0.39). However, both normal tissue types exhibited significant positive correlations for more than 60% of patients, with 41% having moderate to strong correlations (R > 0.5). Conclusion: All lesions showed distinct 18 F-FMISO uptake. Variable 18 F-FMISO delivery was observed across lesions, as indicated by the variable values of the kinetic rate constant K 1 Except for 3 cases, some degree of hypoxia was apparent in all lesions based on their nonzero k 3 values. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Comparing 2-[18F]fluoro-2-deoxy-D-glucose and [68Ga]gallium-citrate translocation in Arabidopsis thaliana.

PubMed

Fatangare, Amol; Gebhardt, Peter; Saluz, Hanspeter; Svatoš, Aleš

2014-10-01

2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) is a glucose surrogate commonly used in clinical or animal imaging but rarely in plant imaging to trace glucose metabolism. Recently, (18)FDG has been employed in plant imaging for studying photoassimilate translocation and glycoside biosynthesis. There is growing evidence that (18)FDG could be used as a tracer in plant imaging studies to trace sugar dynamics. However, to confirm this hypothesis, it was necessary to show that the observed (18)FDG distribution in an intact plant is an outcome of the chemical nature of the introduced radiotracer and not of the plant vascular architecture or radiotracer introduction method. In the present work, we fed (18)FDG and [(68)Ga]gallium-citrate ((68)Ga-citrate) solution through mature Arabidopsis thaliana leaf and monitored subsequent radioactivity distribution using positron autoradiography. The possible route of radioactivity translocation was elucidated through stem-girdling experiments. We also employed a bi-functional positron emission tomography/computed tomography (PET/CT) modality to capture (18)FDG radiotracer dynamics in one of the plants in order to assess applicability of PET/CT for 4-D imaging in an intact plant. Autoradiography results showed that [(18)F] radioactivity accumulated mostly in roots and young growing parts such as the shoot apex, which are known to act as sinks for photoassimilate. [(18)F] radioactivity translocation, in this case, occurred mainly via phloem. PET/CT results corroborated with autoradiography. [(68)Ga] radioactivity, on the other hand, was mainly translocated to neighboring leaves and its translocation occurred via both xylem and phloem. The radioactivity distribution pattern and translocation route observed after (18)FDG feeding is markedly different from that of (68)Ga-citrate. [(18)F] radioactivity distribution pattern in an intact plant is found similar to the typical distribution pattern of photoassimilates. Despite its limitations in quantification and resolution, PET/CT could be a useful tool to elucidate in vivo dynamics of [(18)F] radioactivity in intact plants. Copyright © 2014 Elsevier Inc. All rights reserved.

Methodology for quantitative rapid multi-tracer PET tumor characterizations.

PubMed

Kadrmas, Dan J; Hoffman, John M

2013-10-04

Positron emission tomography (PET) can image a wide variety of functional and physiological parameters in vivo using different radiotracers. As more is learned about the molecular basis for disease and treatment, the potential value of molecular imaging for characterizing and monitoring disease status has increased. Characterizing multiple aspects of tumor physiology by imaging multiple PET tracers in a single patient provides additional complementary information, and there is a significant body of literature supporting the potential value of multi-tracer PET imaging in oncology. However, imaging multiple PET tracers in a single patient presents a number of challenges. A number of techniques are under development for rapidly imaging multiple PET tracers in a single scan, where signal-recovery processing algorithms are employed to recover various imaging endpoints for each tracer. Dynamic imaging is generally used with tracer injections staggered in time, and kinetic constraints are utilized to estimate each tracers' contribution to the multi-tracer imaging signal. This article summarizes past and ongoing work in multi-tracer PET tumor imaging, and then organizes and describes the main algorithmic approaches for achieving multi-tracer PET signal-recovery. While significant advances have been made, the complexity of the approach necessitates protocol design, optimization, and testing for each particular tracer combination and application. Rapid multi-tracer PET techniques have great potential for both research and clinical cancer imaging applications, and continued research in this area is warranted.

Methodology for Quantitative Rapid Multi-Tracer PET Tumor Characterizations

PubMed Central

Kadrmas, Dan J.; Hoffman, John M.

2013-01-01

Positron emission tomography (PET) can image a wide variety of functional and physiological parameters in vivo using different radiotracers. As more is learned about the molecular basis for disease and treatment, the potential value of molecular imaging for characterizing and monitoring disease status has increased. Characterizing multiple aspects of tumor physiology by imaging multiple PET tracers in a single patient provides additional complementary information, and there is a significant body of literature supporting the potential value of multi-tracer PET imaging in oncology. However, imaging multiple PET tracers in a single patient presents a number of challenges. A number of techniques are under development for rapidly imaging multiple PET tracers in a single scan, where signal-recovery processing algorithms are employed to recover various imaging endpoints for each tracer. Dynamic imaging is generally used with tracer injections staggered in time, and kinetic constraints are utilized to estimate each tracers' contribution to the multi-tracer imaging signal. This article summarizes past and ongoing work in multi-tracer PET tumor imaging, and then organizes and describes the main algorithmic approaches for achieving multi-tracer PET signal-recovery. While significant advances have been made, the complexity of the approach necessitates protocol design, optimization, and testing for each particular tracer combination and application. Rapid multi-tracer PET techniques have great potential for both research and clinical cancer imaging applications, and continued research in this area is warranted. PMID:24312149

Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using 18F-fluoromisonidazole PET/CT: a pilot study.

PubMed

Supiot, Stéphane; Rousseau, Caroline; Dore, Mélanie; Cheze-Le-Rest, Catherine; Kandel-Aznar, Christine; Potiron, Vincent; Guerif, Stéphane; Paris, François; Ferrer, Ludovic; Campion, Loïc; Meingan, Philippe; Delpon, Gregory; Hatt, Mathieu; Visvikis, Dimitris

2018-02-09

Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of 18 F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment. Intermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and 18 F-choline-PET. 18 F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation. Of 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUV max and SUV max tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml. This is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.

Joint reconstruction of dynamic PET activity and kinetic parametric images using total variation constrained dictionary sparse coding

NASA Astrophysics Data System (ADS)

Yu, Haiqing; Chen, Shuhang; Chen, Yunmei; Liu, Huafeng

2017-05-01

Dynamic positron emission tomography (PET) is capable of providing both spatial and temporal information of radio tracers in vivo. In this paper, we present a novel joint estimation framework to reconstruct temporal sequences of dynamic PET images and the coefficients characterizing the system impulse response function, from which the associated parametric images of the system macro parameters for tracer kinetics can be estimated. The proposed algorithm, which combines statistical data measurement and tracer kinetic models, integrates a dictionary sparse coding (DSC) into a total variational minimization based algorithm for simultaneous reconstruction of the activity distribution and parametric map from measured emission sinograms. DSC, based on the compartmental theory, provides biologically meaningful regularization, and total variation regularization is incorporated to provide edge-preserving guidance. We rely on techniques from minimization algorithms (the alternating direction method of multipliers) to first generate the estimated activity distributions with sub-optimal kinetic parameter estimates, and then recover the parametric maps given these activity estimates. These coupled iterative steps are repeated as necessary until convergence. Experiments with synthetic, Monte Carlo generated data, and real patient data have been conducted, and the results are very promising.

Machine learning-based kinetic modeling: a robust and reproducible solution for quantitative analysis of dynamic PET data

NASA Astrophysics Data System (ADS)

Pan, Leyun; Cheng, Caixia; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-05-01

A variety of compartment models are used for the quantitative analysis of dynamic positron emission tomography (PET) data. Traditionally, these models use an iterative fitting (IF) method to find the least squares between the measured and calculated values over time, which may encounter some problems such as the overfitting of model parameters and a lack of reproducibility, especially when handling noisy data or error data. In this paper, a machine learning (ML) based kinetic modeling method is introduced, which can fully utilize a historical reference database to build a moderate kinetic model directly dealing with noisy data but not trying to smooth the noise in the image. Also, due to the database, the presented method is capable of automatically adjusting the models using a multi-thread grid parameter searching technique. Furthermore, a candidate competition concept is proposed to combine the advantages of the ML and IF modeling methods, which could find a balance between fitting to historical data and to the unseen target curve. The machine learning based method provides a robust and reproducible solution that is user-independent for VOI-based and pixel-wise quantitative analysis of dynamic PET data.

Machine learning-based kinetic modeling: a robust and reproducible solution for quantitative analysis of dynamic PET data.

PubMed

Pan, Leyun; Cheng, Caixia; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-05-07

A variety of compartment models are used for the quantitative analysis of dynamic positron emission tomography (PET) data. Traditionally, these models use an iterative fitting (IF) method to find the least squares between the measured and calculated values over time, which may encounter some problems such as the overfitting of model parameters and a lack of reproducibility, especially when handling noisy data or error data. In this paper, a machine learning (ML) based kinetic modeling method is introduced, which can fully utilize a historical reference database to build a moderate kinetic model directly dealing with noisy data but not trying to smooth the noise in the image. Also, due to the database, the presented method is capable of automatically adjusting the models using a multi-thread grid parameter searching technique. Furthermore, a candidate competition concept is proposed to combine the advantages of the ML and IF modeling methods, which could find a balance between fitting to historical data and to the unseen target curve. The machine learning based method provides a robust and reproducible solution that is user-independent for VOI-based and pixel-wise quantitative analysis of dynamic PET data.

A Dual Modality System for Simultaneous Fluorescence and Positron Emission Tomography Imaging of Small Animals

NASA Astrophysics Data System (ADS)

Liu, Shuangquan; Zhang, Bin; Wang, Xin; Li, Lin; Chen, Yan; Liu, Xin; Liu, Fei; Shan, Baoci; Bai, Jing

2011-02-01

A dual-modality imaging system for simultaneous fluorescence molecular tomography (FMT) and positron emission tomography (PET) of small animals has been developed. The system consists of a noncontact 360°-projection FMT module and a flat panel detector pair based PET module, which are mounted orthogonally for the sake of eliminating cross interference. The FMT images and PET data are simultaneously acquired by employing dynamic sampling mode. Phantom experiments, in which the localization and range of radioactive and fluorescence probes are exactly indicated, have been carried out to verify the feasibility of the system. An experimental tumor-bearing mouse is also scanned using the dual-modality simultaneous imaging system, the preliminary fluorescence tomographic images and PET images demonstrate the in vivo performance of the presented dual-modality system.

Improved Parameter-Estimation With MRI-Constrained PET Kinetic Modeling: A Simulation Study

NASA Astrophysics Data System (ADS)

Erlandsson, Kjell; Liljeroth, Maria; Atkinson, David; Arridge, Simon; Ourselin, Sebastien; Hutton, Brian F.

2016-10-01

Kinetic analysis can be applied both to dynamic PET and dynamic contrast enhanced (DCE) MRI data. We have investigated the potential of MRI-constrained PET kinetic modeling using simulated [ 18F]2-FDG data for skeletal muscle. The volume of distribution, Ve, for the extra-vascular extra-cellular space (EES) is the link between the two models: It can be estimated by DCE-MRI, and then used to reduce the number of parameters to estimate in the PET model. We used a 3 tissue-compartment model with 5 rate constants (3TC5k), in order to distinguish between EES and the intra-cellular space (ICS). Time-activity curves were generated by simulation using the 3TC5k model for 3 different Ve values under basal and insulin stimulated conditions. Noise was added and the data were fitted with the 2TC3k model and with the 3TC5k model with and without Ve constraint. One hundred noise-realisations were generated at 4 different noise-levels. The results showed reductions in bias and variance with Ve constraint in the 3TC5k model. We calculated the parameter k3", representing the combined effect of glucose transport across the cellular membrane and phosphorylation, as an extra outcome measure. For k3", the average coefficient of variation was reduced from 52% to 9.7%, while for k3 in the standard 2TC3k model it was 3.4%. The accuracy of the parameters estimated with our new modeling approach depends on the accuracy of the assumed Ve value. In conclusion, we have shown that, by utilising information that could be obtained from DCE-MRI in the kinetic analysis of [ 18F]2-FDG-PET data, it is in principle possible to obtain better parameter estimates with a more complex model, which may provide additional information as compared to the standard model.

Multimodal Imaging of Brain Connectivity Using the MIBCA Toolbox: Preliminary Application to Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Ribeiro, André Santos; Lacerda, Luís Miguel; Silva, Nuno André da; Ferreira, Hugo Alexandre

2015-06-01

The Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox is a fully automated all-in-one connectivity analysis toolbox that offers both pre-processing, connectivity, and graph theory analysis of multimodal images such as anatomical, diffusion, and functional MRI, and PET. In this work, the MIBCA functionalities were used to study Alzheimer's Disease (AD) in a multimodal MR/PET approach. Materials and Methods: Data from 12 healthy controls, and 36 patients with EMCI, LMCI and AD (12 patients for each group) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu), including T1-weighted (T1-w), Diffusion Tensor Imaging (DTI) data, and 18F-AV-45 (florbetapir) dynamic PET data from 40-60 min post injection (4x5 min). Both MR and PET data were automatically pre-processed for all subjects using MIBCA. T1-w data was parcellated into cortical and subcortical regions-of-interest (ROIs), and the corresponding thicknesses and volumes were calculated. DTI data was used to compute structural connectivity matrices based on fibers connecting pairs of ROIs. Lastly, dynamic PET images were summed, and the relative Standard Uptake Values calculated for each ROI. Results: An overall higher uptake of 18F-AV-45, consistent with an increased deposition of beta-amyloid, was observed for the AD group. Additionally, patients showed significant cortical atrophy (thickness and volume) especially in the entorhinal cortex and temporal areas, and a significant increase in Mean Diffusivity (MD) in the hippocampus, amygdala and temporal areas. Furthermore, patients showed a reduction of fiber connectivity with the progression of the disease, especially for intra-hemispherical connections. Conclusion: This work shows the potential of the MIBCA toolbox for the study of AD, as findings were shown to be in agreement with the literature. Here, only structural changes and beta-amyloid accumulation were considered. Yet, MIBCA is further able to process fMRI and different radiotracers, thus leading to integration of functional information, and supporting the research for new multimodal biomarkers for AD and other neurodegenerative diseases.

Prediction of tumor differentiation using sequential PET/CT and MRI in patients with breast cancer.

PubMed

Choi, Joon Ho; Lim, Ilhan; Noh, Woo Chul; Kim, Hyun-Ah; Seong, Min-Ki; Jang, Seonah; Seol, Hyesil; Moon, Hansol; Byun, Byung Hyun; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo

2018-05-23

The aim of this study is to assess tumor differentiation using parameters from sequential positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in patients with breast cancer. This retrospective study included 78 patients with breast cancer. All patients underwent sequential PET/CT and MRI. For fluorodeoxyglucose (FDG)-PET image analysis, the maximum standardized uptake value (SUV max ) of FDG was assessed at both 1 and 2 h and metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The kinetic analysis of dynamic contrast-enhanced MRI parameters was performed using dynamic enhancement curves. We assessed diffusion-weighted imaging (DWI)-MRI parameters regarding apparent diffusion coefficient (ADC) values. Histologic grades 1 and 2 were classified as low-grade, and grade 3 as high-grade tumor. Forty-five lesions of 78 patients were classified as histologic grade 3, while 26 and 7 lesions were grade 2 and grade 1, respectively. Patients with high-grade tumors showed significantly lower ADC-mean values than patients with low-grade tumors (0.99 ± 0.19 vs.1.12 ± 0.32, p = 0.007). With respect to SUV max 1, MTV2.5, and TLG2.5, patients with high-grade tumors showed higher values than patients with low-grade tumors: SUV max 1 (7.92 ± 4.5 vs.6.19 ± 3.05, p = 0.099), MTV2.5 (7.90 ± 9.32 vs.4.38 ± 5.10, p = 0.095), and TLG2.5 (40.83 ± 59.17 vs.19.66 ± 26.08, p = 0.082). However, other parameters did not reveal significant differences between low-grade and high-grade malignancies. In receiver-operating characteristic (ROC) curve analysis, ADC-mean values showed the highest area under the curve of 0.681 (95%CI 0.566-0.782) for assessing high-grade malignancy. Lower ADC-mean values may predict the poor differentiation of breast cancer among diverse PET-MRI functional parameters.

Kinetic Analysis of Dynamic Positron Emission Tomography Data using Open-Source Image Processing and Statistical Inference Tools.

PubMed

Hawe, David; Hernández Fernández, Francisco R; O'Suilleabháin, Liam; Huang, Jian; Wolsztynski, Eric; O'Sullivan, Finbarr

2012-05-01

In dynamic mode, positron emission tomography (PET) can be used to track the evolution of injected radio-labelled molecules in living tissue. This is a powerful diagnostic imaging technique that provides a unique opportunity to probe the status of healthy and pathological tissue by examining how it processes substrates. The spatial aspect of PET is well established in the computational statistics literature. This article focuses on its temporal aspect. The interpretation of PET time-course data is complicated because the measured signal is a combination of vascular delivery and tissue retention effects. If the arterial time-course is known, the tissue time-course can typically be expressed in terms of a linear convolution between the arterial time-course and the tissue residue. In statistical terms, the residue function is essentially a survival function - a familiar life-time data construct. Kinetic analysis of PET data is concerned with estimation of the residue and associated functionals such as flow, flux, volume of distribution and transit time summaries. This review emphasises a nonparametric approach to the estimation of the residue based on a piecewise linear form. Rapid implementation of this by quadratic programming is described. The approach provides a reference for statistical assessment of widely used one- and two-compartmental model forms. We illustrate the method with data from two of the most well-established PET radiotracers, (15)O-H(2)O and (18)F-fluorodeoxyglucose, used for assessment of blood perfusion and glucose metabolism respectively. The presentation illustrates the use of two open-source tools, AMIDE and R, for PET scan manipulation and model inference.

Radioembolization and the Dynamic Role of 90Y PET/CT

PubMed Central

Pasciak, Alexander S.; Bourgeois, Austin C.; McKinney, J. Mark; Chang, Ted T.; Osborne, Dustin R.; Acuff, Shelley N.; Bradley, Yong C.

2014-01-01

Before the advent of tomographic imaging, it was postulated that decay of 90 Y to the 0+ excited state of 90Zr may result in emission of a positron–electron pair. While the branching ratio for pair-production is small (~32 × 10−6), PET has been successfully used to image 90 Y in numerous recent patients and phantom studies. 90 Y PET imaging has been performed on a variety of PET/CT systems, with and without time-of-flight (TOF) and/or resolution recovery capabilities as well as on both bismuth-germanate and lutetium yttrium orthosilicate (LYSO)-based scanners. On all systems, resolution and contrast superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity present in LYSO-based PET scanners is a potential limitation associated with accurate quantification of 90 Y. However, intrinsic radioactivity has been shown to have a negligible effect at the high activity concentrations common in 90 Y radioembolization. Accurate quantification is possible on a variety of PET scanner models, with or without TOF, although TOF improves accuracy at lower activity concentrations. Quantitative 90 Y PET images can be transformed into 3-dimensional (3D) maps of absorbed dose based on the premise that the 90 Y activity distribution does not change after infusion. This transformation has been accomplished in several ways, although the most common is with the use of 3D dose-point-kernel convolution. From a clinical standpoint, 90 Y PET provides a superior post-infusion evaluation of treatment technical success owing to its improved resolution. Absorbed dose maps generated from quantitative PET data can be used to predict treatment efficacy and manage patient follow-up. For patients who receive multiple treatments, this information can also be used to provide patient-specific treatment-planning for successive therapies, potentially improving response. The broad utilization of 90 Y PET has the potential to provide a wealth of dose–response information, which may lead to development of improved radioembolization treatment-planning models in the future. PMID:24579065

Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma.

PubMed

Suchorska, Bogdana; Giese, Armin; Biczok, Annamaria; Unterrainer, Marcus; Weller, Michael; Drexler, Mark; Bartenstein, Peter; Schüller, Ulrich; Tonn, Jörg-Christian; Albert, Nathalie L

2018-01-22

Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal time-to-peak (TTPmin) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTPmin analysis provides prognostic information beyond the WHO classification. Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P < 0.001). Further, outcome stratified by TTPmin with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTPmin >17.5 minutes (P < 0.001 for PFS and OS). Lower TBRmax values or the absence of 18F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTPmin was associated with improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group. 18F-FET-PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Positron Emission Tomography studies with [11C]PBR28 in the Healthy Rodent Brain: Validating SUV as an Outcome Measure of Neuroinflammation.

PubMed

Tóth, Miklós; Doorduin, Janine; Häggkvist, Jenny; Varrone, Andrea; Amini, Nahid; Halldin, Christer; Gulyás, Balázs

2015-01-01

Molecular imaging of the 18 kD Translocator protein (TSPO) with positron emission tomography (PET) is of great value for studying neuroinflammation in rodents longitudinally. Quantification of the TSPO in rodents is, however, quite challenging. There is no suitable reference region and the use of plasma-derived input is not an option for longitudinal studies. The aim of this study was therefore to evaluate the use of the standardized uptake value (SUV) as an outcome measure for TSPO imaging in rodent brain PET studies, using [11C]PBR28. In the first part of the study, healthy male Wistar rats (n = 4) were used to determine the correlation between the distribution volume (VT, calculated with Logan graphical analysis) and the SUV. In the second part, healthy male Wistar rats (n = 4) and healthy male C57BL/6J mice (n = 4), were used to determine the test-retest variability of the SUV, with a 7-day interval between measurements. Dynamic PET scans of 63 minutes were acquired with a nanoScan PET/MRI and nanoScan PET/CT. An MRI scan was made for anatomical reference with each measurement. The whole brain VT of [11C]PBR28 in rats was 42.9 ± 1.7. A statistically significant correlation (r2 = 0.96; p < 0.01) was found between the VT and the SUV. The test-retest variability in 8 brain region ranged from 8 to 20% in rats and from 7 to 23% in mice. The interclass correlation coefficient (ICC) was acceptable to excellent for rats, but poor to acceptable for mice. The SUV of [11C]PBR28 showed a high correlation with VT as well as good test-retest variability. For future longitudinal small animal PET studies the SUV can thus be used to describe [11C]PBR28 uptake in healthy brain tissue. Based on the present observations, further studies are needed to explore the applicability of this approach in small animal disease models, with special regard to neuroinflammatory models.

Dynamic Positron Emission Tomography Imaging of Renal Clearable Gold Nanoparticles

PubMed Central

Chen, Feng; Goel, Shreya; Hernandez, Reinier; Graves, Stephen A.; Shi, Sixiang; Nickles, Robert J.; Cai, Weibo

2016-01-01

Optical imaging has been the primary imaging modality for nearly all of the renal clearable nanoparticles since 2007. Due to the tissue depth penetration limitation, providing accurate organ kinetics non-invasively has long been a huge challenge. Although a more quantitative imaging technique has been developed by labeling nanoparticles with single-photon emission computed tomography (SPECT) isotopes, the low temporal resolution of SPECT still limits its potential for visualizing the rapid dynamic process of renal clearable nanoparticles in vivo. Here, we report the dynamic positron emission tomography (PET) imaging of renal clearable gold (Au) nanoparticles by labeling them with copper-64 (64Cu) to form 64Cu-NOTA-Au-GSH. Systematic nanoparticle synthesis and characterizations were performed to demonstrate the efficient renal clearance of as-prepared nanoparticles. A rapid renal clearance of 64Cu-NOTA-Au-GSH was observed (>75 %ID at 24 h post-injection) with its elimination half-life calculated to be less than 6 min, over 130 times shorter than previously reported similar nanoparticles. Dynamic PET imaging not only addresses the current challenges in accurately and non-invasively acquiring the organ kinetics, but also potentially provides a highly useful tool for studying renal clearance mechanism of other ultra-small nanoparticles, as well as the diagnosis of kidney diseases in the near future. PMID:27062146

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

PubMed

Qureshi, N R; Rintoul, R C; Miles, K A; George, S; Harris, S; Madden, J; Cozens, K; Little, L A; Eichhorst, K; Jones, J; Moate, P; McClement, C; Pike, L; Sinclair, D; Wong, W L; Shekhdar, J; Eaton, R; Shah, A; Brindle, L; Peebles, C; Banerjee, A; Dizdarevic, S; Han, S; Poon, F W; Groves, A M; Kurban, L; Frew, A J; Callister, M E; Crosbie, P; Gleeson, F V; Karunasaagarar, K; Kankam, O; Gilbert, F J

2016-01-01

Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) ( 18 FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18 FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. ISRCTN30784948; Pre-results.

Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB-H: First-in-Human Study.

PubMed

Bretin, F; Bahri, M A; Bernard, C; Warnock, G; Aerts, J; Mestdagh, N; Buchanan, T; Otoul, C; Koestler, F; Mievis, F; Giacomelli, F; Degueldre, C; Hustinx, R; Luxen, A; Seret, A; Plenevaux, A; Salmon, E

2015-08-01

[(18)F]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [(18)F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1-156.5 MBq) of [(18)F]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 × 10(-2) ± 6.84 × 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 × 10(-2) ± 2.32 × 10(-3) mGy/MBq. This first human dosimetry study of [(18)F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.

Automatic 3D registration of dynamic stress and rest (82)Rb and flurpiridaz F 18 myocardial perfusion PET data for patient motion detection and correction.

PubMed

Woo, Jonghye; Tamarappoo, Balaji; Dey, Damini; Nakazato, Ryo; Le Meunier, Ludovic; Ramesh, Amit; Lazewatsky, Joel; Germano, Guido; Berman, Daniel S; Slomka, Piotr J

2011-11-01

The authors aimed to develop an image-based registration scheme to detect and correct patient motion in stress and rest cardiac positron emission tomography (PET)/CT images. The patient motion correction was of primary interest and the effects of patient motion with the use of flurpiridaz F 18 and (82)Rb were demonstrated. The authors evaluated stress/rest PET myocardial perfusion imaging datasets in 30 patients (60 datasets in total, 21 male and 9 female) using a new perfusion agent (flurpiridaz F 18) (n = 16) and (82)Rb (n = 14), acquired on a Siemens Biograph-64 scanner in list mode. Stress and rest images were reconstructed into 4 ((82)Rb) or 10 (flurpiridaz F 18) dynamic frames (60 s each) using standard reconstruction (2D attenuation weighted ordered subsets expectation maximization). Patient motion correction was achieved by an image-based registration scheme optimizing a cost function using modified normalized cross-correlation that combined global and local features. For comparison, visual scoring of motion was performed on the scale of 0 to 2 (no motion, moderate motion, and large motion) by two experienced observers. The proposed registration technique had a 93% success rate in removing left ventricular motion, as visually assessed. The maximum detected motion extent for stress and rest were 5.2 mm and 4.9 mm for flurpiridaz F 18 perfusion and 3.0 mm and 4.3 mm for (82)Rb perfusion studies, respectively. Motion extent (maximum frame-to-frame displacement) obtained for stress and rest were (2.2 ± 1.1, 1.4 ± 0.7, 1.9 ± 1.3) mm and (2.0 ± 1.1, 1.2 ±0 .9, 1.9 ± 0.9) mm for flurpiridaz F 18 perfusion studies and (1.9 ± 0.7, 0.7 ± 0.6, 1.3 ± 0.6) mm and (2.0 ± 0.9, 0.6 ± 0.4, 1.2 ± 1.2) mm for (82)Rb perfusion studies, respectively. A visually detectable patient motion threshold was established to be ≥2.2 mm, corresponding to visual user scores of 1 and 2. After motion correction, the average increases in contrast-to-noise ratio (CNR) from all frames for larger than the motion threshold were 16.2% in stress flurpiridaz F 18 and 12.2% in rest flurpiridaz F 18 studies. The average increases in CNR were 4.6% in stress (82)Rb studies and 4.3% in rest (82)Rb studies. Fully automatic motion correction of dynamic PET frames can be performed accurately, potentially allowing improved image quantification of cardiac PET data.

Changes in effective moisture on the Tibetan Plateau during the period 1981-2010

NASA Astrophysics Data System (ADS)

Yin, Y.; Wu, S.; Zhao, D.

2013-12-01

Observed evaporative demand has decreased worldwide during the past several decades. This trend is also noted on the Tibetan Plateau, a region that is particularly sensitive to climate change. However, actual evapotranspiration trends and their relationship to drought stress on the Tibetan Plateau are poorly understood. We analyzed the spatiotemporal changes in potential evapotranspiration(PET), actual evapotranspiration(AET) and effective moisture (defined as AET/PET) during 1981-2010. Climate data from 80 meteorological stations on the Tibetan Plateau were compiled for the period 1981-2010. New plant functional types were defined for the Tibetan Plateau and evapotranspiration is simulated by the modified Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ). The results show regional trends towards decreasing PET and statistically significant increases in AET (p < 0.05) and effective moisture (p < 0.001) during the period 1981-2010. A transition from significant negative to positive PET occurred in 1997. Additionally, a pronounced increase in effective moisture occurred during the period 1981-1997 because of significant decreased PET before 1997.

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Fritz, Josef; Decristoforo, Clemens; Kendler, Dorota; von Guggenberg, Elisabeth; Nilica, Bernhard; Maffey-Steffan, Johanna; di Santo, Gianpaolo; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-09-01

PET/CT using 68 Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68 Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68 Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i.. 203 consecutive PC patients with biochemical failure referred to 68 Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243-491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUV max ) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans. 26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUV max : 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUV max : 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUV max of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281-491 vs. 243-311 s p.i.; p < 0.001). Median SUV max value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUV max : 5.9 vs. 1.9, 4.0 and 2.4, respectively). Performance of early imaging in 68 Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence.

PubMed

Steiner, Ch; Vees, H; Zaidi, H; Wissmeyer, M; Berrebi, O; Kossovsky, M P; Khan, H G; Miralbell, R; Ratib, O; Buchegger, F

2009-01-01

Contribution of 3-phase 18F-fluorocholine PET/CT in suspected prostate cancer recurrence at early rise of PSA. Retrospective analysis was performed in 47 patients after initial treatment with radiotherapy (n=30) or surgery (n=17). Following CT, 10 minutes list-mode PET acquisition was done over the prostate bed after injection of 300 MBq of 18F-fluorocholine. Three timeframes of 3 minutes each were reconstructed for analysis. All patients underwent subsequent whole body PET/CT. Delayed pelvic PET/CT was obtained in 36 patients. PET/CT was interpreted visually by two observers and SUVmax determined for suspicious lesions. Biopsies were obtained from 13 patients. Biopsies confirmed the presence of cancer in 11 of 13 patients with positive PET for a total of 15 local recurrences in which average SUVmax increased during 14 minutes post injection and marginally decreased in delayed scanning. Conversely inguinal lymph nodes with mild to moderate metabolic activity on PET showed a clearly different pattern with decreasing SUVmax on dynamic images. Three-phase PET/CT contributed to the diagnostic assessment of 10 of 47 patients with biological evidence of recurrence of cancer. It notably allowed the discrimination of confounding blood pool or urinary activity from suspicious hyperactivities. PET/CT was positive in all patients with PSA>or=2 ng/ml (n=34) and in 4/13 patients presenting PSA values<2 ng/ml. 18F-fluorocholine 3-phase PET/CT showed a progressively increasing SUVmax in biopsy confirmed cancer lesions up to 14 minutes post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.

First-Pass Angiography in Mice Using FDG-PET: A Simple Method of Deriving the Cardiovascular Transit Time Without the Need of Region-of-Interest Drawing.

PubMed

Wu, Hsiao-Ming; Kreissl, Michael C; Schelbert, Heinrich R; Ladno, Waldemar; Prins, Mayumi; Shoghi-Jadid, Kooresh; Chatziioannou, Arion; Phelps, Michael E; Huang, Sung-Cheng

2005-10-01

In this study, we developed a simple and robust semi-automatic method to measure the right ventricle to left ventricle (RV-to-LV) transit time (TT) in mice using 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). The accuracy of the method was first evaluated using a 4-D digital dynamic mouse phantom. The RV-to-LV TTs of twenty-nine mouse studies were measured using the new method and compared to those obtained from the conventional ROI-drawing method. The results showed that the new method correctly separated different structures (e.g., RV, lung, and LV) in the PET images and generated corresponding time activity curve (TAC) of each structure. The RV-to-LV TTs obtained from the new method and ROI method were not statistically different (P = 0.20; r = 0.76). We expect that this fast and robust method is applicable to the pathophysiology of cardiovascular diseases using small animal models such as rats and mice.

SU-C-9A-06: The Impact of CT Image Used for Attenuation Correction in 4D-PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Y; Bowsher, J; Yan, S

2014-06-01

Purpose: To evaluate the appropriateness of using 3D non-gated CT image for attenuation correction (AC) in a 4D-PET (gated PET) imaging protocol used in radiotherapy treatment planning simulation. Methods: The 4D-PET imaging protocol in a Siemens PET/CT simulator (Biograph mCT, Siemens Medical Solutions, Hoffman Estates, IL) was evaluated. CIRS Dynamic Thorax Phantom (CIRS Inc., Norfolk, VA) with a moving glass sphere (8 mL) in the middle of its thorax portion was used in the experiments. The glass was filled with {sup 18}F-FDG and was in a longitudinal motion derived from a real patient breathing pattern. Varian RPM system (Varian Medicalmore » Systems, Palo Alto, CA) was used for respiratory gating. Both phase-gating and amplitude-gating methods were tested. The clinical imaging protocol was modified to use three different CT images for AC in 4D-PET reconstruction: first is to use a single-phase CT image to mimic actual clinical protocol (single-CT-PET); second is to use the average intensity projection CT (AveIP-CT) derived from 4D-CT scanning (AveIP-CT-PET); third is to use 4D-CT image to do the phase-matched AC (phase-matching- PET). Maximum SUV (SUVmax) and volume of the moving target (glass sphere) with threshold of 40% SUVmax were calculated for comparison between 4D-PET images derived with different AC methods. Results: The SUVmax varied 7.3%±6.9% over the breathing cycle in single-CT-PET, compared to 2.5%±2.8% in AveIP-CT-PET and 1.3%±1.2% in phasematching PET. The SUVmax in single-CT-PET differed by up to 15% from those in phase-matching-PET. The target volumes measured from single- CT-PET images also presented variations up to 10% among different phases of 4D PET in both phase-gating and amplitude-gating experiments. Conclusion: Attenuation correction using non-gated CT in 4D-PET imaging is not optimal process for quantitative analysis. Clinical 4D-PET imaging protocols should consider phase-matched 4D-CT image if available to achieve better accuracy.« less

Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

NASA Astrophysics Data System (ADS)

Winant, Celeste D.; Aparici, Carina Mari; Zelnik, Yuval R.; Reutter, Bryan W.; Sitek, Arkadiusz; Bacharach, Stephen L.; Gullberg, Grant T.

2012-01-01

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic 94Tc-methoxyisobutylisonitrile (94Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K1 for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K1. For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from 94Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of 99mTc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum-likelihood expectation-maximization (4D ML-EM) reconstructions gave more accurate reconstructions than did standard frame-by-frame static 3D ML-EM reconstructions. The SPECT/P results showed that 4D ML-EM reconstruction gave higher and more accurate estimates of K1 than did 3D ML-EM, yielding anywhere from a 44% underestimation to 24% overestimation for the three patients. The SPECT/D results showed that 4D ML-EM reconstruction gave an overestimation of 28% and 3D ML-EM gave an underestimation of 1% for K1. For the patient study the 4D ML-EM reconstruction provided continuous images as a function of time of the concentration in both ventricular cavities and myocardium during the 2 min infusion. It is demonstrated that a 2 min infusion with a two-headed SPECT system rotating 180° every 54 s can produce measurements of blood pool and myocardial TACs, though the SPECT simulation studies showed that one must sample at least every 30 s to capture a 1 min infusion input function.

In vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: a new tool for oncology and radiotracer development.

PubMed

Warnock, Geoff; Turtoi, Andrei; Blomme, Arnaud; Bretin, Florian; Bahri, Mohamed Ali; Lemaire, Christian; Libert, Lionel Cyrille; Seret, Alain E J J; Luxen, André; Castronovo, Vincenzo; Plenevaux, Alain R E G

2013-10-01

For many years the laboratory mouse has been used as the standard model for in vivo oncology research, particularly in the development of novel PET tracers, but the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more rapid, low cost, and ethically sustainable alternative. For the first time, to our knowledge, we demonstrate the feasibility of in vivo PET and CT imaging in a U87 glioblastoma tumor model on chicken CAM, with the aim of applying this model for screening of novel PET tracers. U87 glioblastoma cells were implanted on the CAM at day 11 after fertilization and imaged at day 18. A small-animal imaging cell was used to maintain incubation and allow anesthesia using isoflurane. Radiotracers were injected directly into the exposed CAM vasculature. Sodium (18)F-fluoride was used to validate the imaging protocol, demonstrating that image-degrading motion can be removed with anesthesia. Tumor glucose metabolism was imaged using (18)F-FDG, and tumor protein synthesis was imaged using 2-(18)F-fluoro-l-tyrosine. Anatomic images were obtained by contrast-enhanced CT, facilitating clear delineation of the tumor, delineation of tracer uptake in tumor versus embryo, and accurate volume measurements. PET imaging of tumor glucose metabolism and protein synthesis was successfully demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood vessels facilitated dynamic imaging of glucose metabolism with (18)F-FDG and demonstrated the ability to study PET tracer uptake over time in individual tumors, and CT imaging improved the accuracy of tumor volume measurements. We describe the novel application of PET/CT in the CAM tumor model, with optimization of typical imaging protocols. PET imaging in this valuable tumor model could prove particularly useful for rapid, high-throughput screening of novel radiotracers.

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex.

PubMed

Hennessy, Morgan L; Corcoran, Andrea E; Brust, Rachael D; Chang, YoonJeung; Nattie, Eugene E; Dymecki, Susan M

2017-02-15

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 ( Tac1 ) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1 , referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine -N- oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 ( Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO 2 Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. Copyright © 2017 the authors 0270-6474/17/371807-13$15.00/0.

18F-fluorocholine PET-guided target volume delineation techniques for partial prostate re-irradiation in local recurrent prostate cancer.

PubMed

Wang, Hui; Vees, Hansjörg; Miralbell, Raymond; Wissmeyer, Michael; Steiner, Charles; Ratib, Osman; Senthamizhchelvan, Srinivasan; Zaidi, Habib

2009-11-01

We evaluate the contribution of (18)F-choline PET/CT in the delineation of gross tumour volume (GTV) in local recurrent prostate cancer after initial irradiation using various PET image segmentation techniques. Seventeen patients with local-only recurrent prostate cancer (median=5.7 years) after initial irradiation were included in the study. Rebiopsies were performed in 10 patients that confirmed the local recurrence. Following injection of 300 MBq of (18)F-fluorocholine, dynamic PET frames (3 min each) were reconstructed from the list-mode acquisition. Five PET image segmentation techniques were used to delineate the (18)F-choline-based GTVs. These included manual delineation of contours (GTV(man)) by two teams consisting of a radiation oncologist and a nuclear medicine physician each, a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio-based adaptive thresholding (GTV(SBR)), and a region growing (GTV(RG)) algorithm. Geographic mismatches between the GTVs were also assessed using overlap analysis. Inter-observer variability for manual delineation of GTVs was high but not statistically significant (p=0.459). In addition, the volumes and shapes of GTVs delineated using semi-automated techniques were significantly higher than those of GTVs defined manually. Semi-automated segmentation techniques for (18)F-choline PET-guided GTV delineation resulted in substantially higher GTVs compared to manual delineation and might replace the latter for determination of recurrent prostate cancer for partial prostate re-irradiation. The selection of the most appropriate segmentation algorithm still needs to be determined.

Impact of time-of-flight on indirect 3D and direct 4D parametric image reconstruction in the presence of inconsistent dynamic PET data.

PubMed

Kotasidis, F A; Mehranian, A; Zaidi, H

2016-05-07

Kinetic parameter estimation in dynamic PET suffers from reduced accuracy and precision when parametric maps are estimated using kinetic modelling following image reconstruction of the dynamic data. Direct approaches to parameter estimation attempt to directly estimate the kinetic parameters from the measured dynamic data within a unified framework. Such image reconstruction methods have been shown to generate parametric maps of improved precision and accuracy in dynamic PET. However, due to the interleaving between the tomographic and kinetic modelling steps, any tomographic or kinetic modelling errors in certain regions or frames, tend to spatially or temporally propagate. This results in biased kinetic parameters and thus limits the benefits of such direct methods. Kinetic modelling errors originate from the inability to construct a common single kinetic model for the entire field-of-view, and such errors in erroneously modelled regions could spatially propagate. Adaptive models have been used within 4D image reconstruction to mitigate the problem, though they are complex and difficult to optimize. Tomographic errors in dynamic imaging on the other hand, can originate from involuntary patient motion between dynamic frames, as well as from emission/transmission mismatch. Motion correction schemes can be used, however, if residual errors exist or motion correction is not included in the study protocol, errors in the affected dynamic frames could potentially propagate either temporally, to other frames during the kinetic modelling step or spatially, during the tomographic step. In this work, we demonstrate a new strategy to minimize such error propagation in direct 4D image reconstruction, focusing on the tomographic step rather than the kinetic modelling step, by incorporating time-of-flight (TOF) within a direct 4D reconstruction framework. Using ever improving TOF resolutions (580 ps, 440 ps, 300 ps and 160 ps), we demonstrate that direct 4D TOF image reconstruction can substantially prevent kinetic parameter error propagation either from erroneous kinetic modelling, inter-frame motion or emission/transmission mismatch. Furthermore, we demonstrate the benefits of TOF in parameter estimation when conventional post-reconstruction (3D) methods are used and compare the potential improvements to direct 4D methods. Further improvements could possibly be achieved in the future by combining TOF direct 4D image reconstruction with adaptive kinetic models and inter-frame motion correction schemes.

Impact of time-of-flight on indirect 3D and direct 4D parametric image reconstruction in the presence of inconsistent dynamic PET data

NASA Astrophysics Data System (ADS)

Kotasidis, F. A.; Mehranian, A.; Zaidi, H.

2016-05-01

Kinetic parameter estimation in dynamic PET suffers from reduced accuracy and precision when parametric maps are estimated using kinetic modelling following image reconstruction of the dynamic data. Direct approaches to parameter estimation attempt to directly estimate the kinetic parameters from the measured dynamic data within a unified framework. Such image reconstruction methods have been shown to generate parametric maps of improved precision and accuracy in dynamic PET. However, due to the interleaving between the tomographic and kinetic modelling steps, any tomographic or kinetic modelling errors in certain regions or frames, tend to spatially or temporally propagate. This results in biased kinetic parameters and thus limits the benefits of such direct methods. Kinetic modelling errors originate from the inability to construct a common single kinetic model for the entire field-of-view, and such errors in erroneously modelled regions could spatially propagate. Adaptive models have been used within 4D image reconstruction to mitigate the problem, though they are complex and difficult to optimize. Tomographic errors in dynamic imaging on the other hand, can originate from involuntary patient motion between dynamic frames, as well as from emission/transmission mismatch. Motion correction schemes can be used, however, if residual errors exist or motion correction is not included in the study protocol, errors in the affected dynamic frames could potentially propagate either temporally, to other frames during the kinetic modelling step or spatially, during the tomographic step. In this work, we demonstrate a new strategy to minimize such error propagation in direct 4D image reconstruction, focusing on the tomographic step rather than the kinetic modelling step, by incorporating time-of-flight (TOF) within a direct 4D reconstruction framework. Using ever improving TOF resolutions (580 ps, 440 ps, 300 ps and 160 ps), we demonstrate that direct 4D TOF image reconstruction can substantially prevent kinetic parameter error propagation either from erroneous kinetic modelling, inter-frame motion or emission/transmission mismatch. Furthermore, we demonstrate the benefits of TOF in parameter estimation when conventional post-reconstruction (3D) methods are used and compare the potential improvements to direct 4D methods. Further improvements could possibly be achieved in the future by combining TOF direct 4D image reconstruction with adaptive kinetic models and inter-frame motion correction schemes.

Real-time iterative monitoring of radiofrequency ablation tumor therapy with 15O-water PET imaging.

PubMed

Bao, Ande; Goins, Beth; Dodd, Gerald D; Soundararajan, Anuradha; Santoyo, Cristina; Otto, Randal A; Davis, Michael D; Phillips, William T

2008-10-01

A method that provides real-time image-based monitoring of solid tumor therapy to ensure complete tumor eradication during image-guided interventional therapy would be a valuable tool. The short, 2-min half-life of (15)O makes it possible to perform repeated PET imaging at 20-min intervals at multiple time points before and after image-guided therapy. In this study, (15)O-water PET was evaluated as a tool to provide real-time feedback and iterative image guidance to rapidly monitor the intratumoral coverage of radiofrequency (RF) ablation therapy. Tumor RF ablation therapy was performed on head and neck squamous cell carcinoma (SCC) xenograft tumors (length, approximately 23 mm) in 6 nude rats. The tumor in each animal was ablated with RF (1-cm active size ablation catheter, 70 degrees C for 5 min) twice in 2 separate tumor regions with a 20-min separation. The (15)O-water PET images were acquired before RF ablation and after the first RF and second RF ablations using a small-animal PET scanner. In each PET session, approximately 100 MBq of (15)O-water in 1.0 mL of saline were injected intravenously into each animal. List-mode PET images were acquired for 7 min starting 20 s before injection. PET images were reconstructed by 2-dimensional ordered-subset expectation maximization into single-frame images and dynamic images at 10 s/frame. PET images were displayed and analyzed with software. Pre-RF ablation images demonstrate that (15)O-water accumulates in tumors with (15)O activity reaching peak levels immediately after administration. After RF ablation, the ablated region had almost zero activity, whereas the unablated tumor tissue continued to have a high (15)O-water accumulation. Using image feedback, the RF probe was repositioned to a tumor region with residual (15)O-water uptake and then ablated. The second RF ablation in this new region of the tumor resulted in additional ablation of the solid tumor, with a corresponding decrease in activity on the (15)O-water PET image. (15)O-water PET clearly demonstrated the ablated tumor region, whereas the unablated tumor continued to show high (15)O-water accumulation. (15)O-water imaging shows promise as a tool for on-site, real-time monitoring of image-guided interventional cancer therapy.

Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer.

PubMed

Park, Sonya Youngju; Zacharias, Claudia; Harrison, Caitlyn; Fan, Richard E; Kunder, Christian; Hatami, Negin; Giesel, Frederik; Ghanouni, Pejman; Daniel, Bruce; Loening, Andreas M; Sonn, Geoffrey A; Iagaru, Andrei

2018-05-16

Purpose To report the results of dual-time-point gallium 68 ( 68 Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68 Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUV max ]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68 Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68 Ga-PSMA-11 increased at later acquisition times, with higher mean SUV max (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68 Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68 Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection. © RSNA, 2018 Online supplemental material is available for this article.

Kinetic Modelling of Infection Tracers [18F]FDG, [68Ga]Ga-Citrate, [11C]Methionine, and [11C]Donepezil in a Porcine Osteomyelitis Model.

PubMed

Jødal, Lars; Jensen, Svend B; Nielsen, Ole L; Afzelius, Pia; Borghammer, Per; Alstrup, Aage K O; Hansen, Søren B

2017-01-01

Positron emission tomography (PET) is increasingly applied for infection imaging using [ 18 F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [ 18 F]FDG and three other PET tracers with relevance for infection imaging. A juvenile porcine osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [ 18 F]FDG, [ 68 Ga]Ga-citrate, [ 11 C]methionine, and/or [ 11 C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer. Irreversible uptake was found for [ 18 F]FDG and [ 68 Ga]Ga-citrate; reversible uptake was found for [ 11 C]methionine (two-tissue model) and [ 11 C]donepezil (one-tissue model). The uptake rate for [ 68 Ga]Ga-citrate was slow and diffusion-limited. For the other tracers, the uptake rate was primarily determined by perfusion (flow-limited uptake). Net uptake rate for [ 18 F]FDG and distribution volume for [ 11 C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue. For [ 11 C]donepezil in pigs, labelled metabolite products appeared to be important for the analysis. The kinetics of the four studied tracers in infection was characterized. For clinical applications, [ 18 F]FDG remains the first-choice PET tracer. [ 11 C]methionine may have a potential for detecting soft tissue infections. [ 68 Ga]Ga-citrate and [ 11 C]donepezil were not found useful for imaging of osteomyelitis.

First PET Imaging Studies With 63Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease.

PubMed

DeGrado, Timothy R; Kemp, Bradley J; Pandey, Mukesh K; Jiang, Huailei; Gunderson, Tina M; Linscheid, Logan R; Woodwick, Allison R; McConnell, Daniel M; Fletcher, Joel G; Johnson, Geoffrey B; Petersen, Ronald C; Knopman, David S; Lowe, Val J

2016-01-01

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63 Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63 Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63 Zn clearances were compared with 11 C-Pittsburgh Compound B ( 11 C-PiB) and 18 F-fluorodeoxyglucose ( 18 F-FDG) imaging data. 63 Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63 Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11 C-PiB) and 18 F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63 Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD. © The Author(s) 2016.

First PET Imaging Studies With 63 Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease

DOE PAGES

DeGrado, Timothy R.; Kemp, Bradley J.; Pandey, Mukesh K.; ...

2016-01-01

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. A dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (~330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B ( 11C-PiB) andmore » 18F-fluorodeoxyglucose ( 18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.« less

Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney

PubMed Central

Hato, Takashi; Friedman, Allon N.; Mang, Henry; Plotkin, Zoya; Dube, Shataakshi; Hutchins, Gary D.; Territo, Paul R.; McCarthy, Brian P.; Riley, Amanda A.; Pichumani, Kumar; Malloy, Craig R.; Harris, Robert A.; Dagher, Pierre C.

2016-01-01

The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical 18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism. PMID:26764206

Positron emission tomography: a novel technique for investigating the biodistribution and transport of nanoparticles.

PubMed

Palko, Heather A; Fung, Jennifer Y; Louie, Angelique Y

2010-07-01

Particulate matter (PM) has been associated with serious health effects within but also outside of the pulmonary system. Therefore, there is great interest in studying the biodistribution of PM after delivery to the lung to correlate sites of extrapulmonary particle accumulation and abnormal conditions known to be associated with PM exposure. Traditional PM tracking studies have introduced nanoparticles to animal models or humans and have determined the biodistribution with gamma counting, gamma camera, and inductively coupled plasma mass spectrometry (ICP-MS). The authors here demonstrate that positron emission tomography (PET) is a powerful tool that can be employed to visualize the deposition and track the fate of nanoparticles in the mouse model. In these studies, approximately 100-nm polystyrene nanoparticles were labeled with the positron emitter 64Cu bound by the chelator (S)-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The labeled nanoparticles were instilled intratracheally into C57BL/6 mice; the initial deposition and biodistribution through 48 h was determined by PET imaging. In addition to static imaging, dynamic imaging was performed in the Sprague-Dawley rat model to demonstrate that PET can capture particle movement in pseudo-time-lapse videos. Particle deposition and clearance was clearly identified by PET, and the same animals could be imaged repeatedly without any adverse effects from anesthesia. PET has the potential to require many fewer animals than traditional methods while still providing quantitative results. In addition, the initial deposition pattern in each animal can be accurately determined and the same animal monitored over time so that data interpretation is not clouded by variations in initial deposition profiles.

Wavelet compression of noisy tomographic images

NASA Astrophysics Data System (ADS)

Kappeler, Christian; Mueller, Stefan P.

1995-09-01

3D data acquisition is increasingly used in positron emission tomography (PET) to collect a larger fraction of the emitted radiation. A major practical difficulty with data storage and transmission in 3D-PET is the large size of the data sets. A typical dynamic study contains about 200 Mbyte of data. PET images inherently have a high level of photon noise and therefore usually are evaluated after being processed by a smoothing filter. In this work we examined lossy compression schemes under the postulate not induce image modifications exceeding those resulting from low pass filtering. The standard we will refer to is the Hanning filter. Resolution and inhomogeneity serve as figures of merit for quantification of image quality. The images to be compressed are transformed to a wavelet representation using Daubechies12 wavelets and compressed after filtering by thresholding. We do not include further compression by quantization and coding here. Achievable compression factors at this level of processing are thirty to fifty.

Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

PubMed

Schwarzenböck, Sarah Marie; Schmeja, Philipp; Kurth, Jens; Souvatzoglou, Michael; Nawroth, Roman; Treiber, Uwe; Kundt, Guenther; Berndt, Sandra; Graham, Keith; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Ziegler, Sibylle I; Dinkelborg, Ludger; Wester, Hans-Jürgen; Krause, Bernd Joachim

2016-06-01

Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C]CHO. The T/M ratio as well as the T/B ratio for [(18)F]Bombesin were significantly higher compared to those for [(11)C]CHO (p < 0.001, respectively). Kidney and liver uptake was statistically significantly lower for [(18)F]Bombesin (K/B 3.41 ± 0.81, L/B 1.99 ± 0.38) compared to [(11)C]CHO [K/B 7.91 ± 1.85 (p < 0.001), L/B 6.27 ± 1.99 (p < 0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [(18)F]Bombesin compared to [(11)C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0.026 and p < 0.001, respectively). [(18)F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [(11)C]CHO in the PC-3 prostate cancer xenograft model. [(18)F]Bombesin tumor uptake was significantly higher compared to [(11)C]CHO. [(18)F]Bombesin showed better imaging properties compared to the clinically utilized [(11)C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.

Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

PubMed

Schepis, Tiziano; Gaemperli, Oliver; Treyer, Valerie; Valenta, Ines; Burger, Cyrill; Koepfli, Pascal; Namdar, Mehdi; Adachi, Itaru; Alkadhi, Hatem; Kaufmann, Philipp A

2007-11-01

The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps < 0.0001). The mean +/- SD differences in global MBF measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P < 0.001). For this scanner type, quantitative measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.

N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats.

PubMed

Frisch, Kim; Stimson, Damion H R; Venkatachalam, Taracad; Pierens, Gregory K; Keiding, Susanne; Reutens, David; Bhalla, Rajiv

2018-05-04

Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[ 18 F]fluorobenzyl)cholylglycine ([ 18 F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [ 18 F]FBCGly and a proof-of-concept study by PET/MR in rats. A radiosynthesis of [ 18 F]FBCGly was developed based on reductive alkylation of glycine with 4-[ 18 F]fluorobenzaldehyde followed by coupling to cholic acid. [ 18 F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [ 18 F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [ 18 F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro. [ 18 F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [ 18 F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [ 18 F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [ 18 F]FBCGly. No fluorine-18 metabolites of [ 18 F]FBCGly were observed. We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [ 18 F]FBCGly, and shown by PET/MR that [ 18 F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids. Copyright © 2018 Elsevier Inc. All rights reserved.

MO-AB-BRA-06: Dynamic FLT PET for Investigating Potential Synergistic Therapeutic Targets During Anti-Angiogenic Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scarpelli, M; Perlman, S; Liu, G

2016-06-15

Purpose: Novel treatment strategies for metastatic cancer patients involve synergistically combining treatments with the hope of improving outcomes. This study investigated changes in tumor proliferative and vascular characteristics derived from dynamic [F-18]FLT PET during antiangiogenic treatment with the goal of identifying synergistic treatment opportunities. Methods: Patients with various solid cancers underwent continuous three-week cycles of anti-angiogenic treatment with intermittent dosing (two-weeks-on/one-week-off). Patients received up to six dynamic FLT PET/CT scans (days 0, 14, and 21 of cycle 1 (C1) and cycle 3 (C3)). Tumor proliferative (Kflt, net uptake rate) and vascular parameters (K1 blood-to-tissue transfer; Vb, vascular fraction) were calculatedmore » using a two-tissue compartment four-rate parameter kinetic model. Relative changes in these parameters, from day 0 to 14 (TxResp) and day 14 to 21 (offTxResp), were calculated. Significant differences were tested using Wilcoxon signed-rank test and significant correlations were tested using Spearman correlation. Results: Thirty patients were evaluable for C1 offTxResp with median values for Kflt, K1, and Vb of +30%, +35% and +30%, respectively. The fractions of patients with positive C1 offTxResp were: 21/30 for Ki, 24/30 for K1, 21/30 for Vb, and 12/30 had positive offTxResp for all three kinetic parameters. The offTxResp in C3 was not significantly different from C1 for any of the kinetic parameters. Significant correlations were found between TxResp and offTxResp in C1 for Kflt (ρ=-0.52, p=0.014), K1 (ρ=−0.61, p=0.003) and Vb (ρ=−0.80, p<0.001). Similar correlations were found for Kflt (ρ=-1, p=0.017) and K1 (ρ=−1, p=0.017) for the five patients evaluable in C3. Conclusion: Dynamic FLT PET showed evidence of distinct vascular and proliferative increases during off treatment weeks that could potentially be targeted with synergistic therapy. Early changes in kinetic parameters were correlated with later changes suggesting potential for early prediction of vascular and proliferative changes during off treatment weeks.« less

The Financial Costs, Behaviour and Psychology of Obesity: A One Health Analysis.

PubMed

Bomberg, E; Birch, L; Endenburg, N; German, A J; Neilson, J; Seligman, H; Takashima, G; Day, M J

2017-05-01

People who are overweight or have obesity are estimated to comprise 30% of the global population and up to 59% of companion dogs and cats are estimated to be above their optimal body weight. The prevalence of human and companion obesity is increasing. The direct and indirect costs of obesity and associated comorbidities are significant for human and veterinary healthcare. There are numerous similarities between obesity in people and companion animals, likely related to the shared environmental and lifestyle elements of this multifactorial disease. While the study of human obesity is relatively robust, research conducted in pets is generally limited to small studies, studies with cross-sectional designs or reports that have yet to be replicated. Greater understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. In particular, there are overlapping features of obesity in children and pets that are, in part, related to dependency on their 'parents' for care and feeding. When feeding is used in a coercive and controlling fashion, it may lead to undesirable feeding behaviour and increase the risk for obesity. A 'responsive parenting' intervention teaches parents to respond appropriately to hunger-satiety cues and to recognize and respond to others' distress. Such interventions may impact on childhood overweight and obesity and have the potential to be adapted for use with companion animals. Social behaviour towards people with obesity or owners of pets with obesity is often driven by beliefs about the cause of the obesity. Educating healthcare professionals and the public about the multifactorial nature of this complex disease process is a fundamental step in reducing the bias and stigma associated with obesity. Children living in low-income households have particularly high rates of obesity and as household income falls, rates of obesity also rise in pets and their owners. There are risk regulators (i.e. dynamic components of interconnected systems that influence obesity-related behaviours) and internal factors (i.e. biological determinants of obesity) that may influence the development of both childhood and pet obesity, and poverty may intersect with these variables to exacerbate obesity in low-income environments. This review discusses the costs, behaviours and psychology related to obesity in people and pets, and also proposes potential techniques that can be considered for prevention and treatment of this disease in pets. A 'One Health' approach to obesity suggests that an understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Accurate analysis and visualization of cardiac (11)C-PIB uptake in amyloidosis with semiautomatic software.

PubMed

Kero, Tanja; Lindsjö, Lars; Sörensen, Jens; Lubberink, Mark

2016-08-01

(11)C-PIB PET is a promising non-invasive diagnostic tool for cardiac amyloidosis. Semiautomatic analysis of PET data is now available but it is not known how accurate these methods are for amyloid imaging. The aim of this study was to evaluate the feasibility of one semiautomatic software tool for analysis and visualization of (11)C-PIB left ventricular retention index (RI) in cardiac amyloidosis. Patients with systemic amyloidosis and cardiac involvement (n = 10) and healthy controls (n = 5) were investigated with dynamic (11)C-PIB PET. Two observers analyzed the PET studies with semiautomatic software to calculate the left ventricular RI of (11)C-PIB and to create parametric images. The mean RI at 15-25 min from the semiautomatic analysis was compared with RI based on manual analysis and showed comparable values (0.056 vs 0.054 min(-1) for amyloidosis patients and 0.024 vs 0.025 min(-1) in healthy controls; P = .78) and the correlation was excellent (r = 0.98). Inter-reader reproducibility also was excellent (intraclass correlation coefficient, ICC > 0.98). Parametric polarmaps and histograms made visual separation of amyloidosis patients and healthy controls fast and simple. Accurate semiautomatic analysis of cardiac (11)C-PIB RI in amyloidosis patients is feasible. Parametric polarmaps and histograms make visual interpretation fast and simple.

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

PubMed Central

Paul, Soumen; Zhang, Dali; Mzengeza, Shadreck; Ko, Ji Hyun

2016-01-01

ABSTRACT 2–18F‐fluorodeoxy‐D‐glucose (FDG) is a glucose analog that is taken up by cells and phosphorylated. The amount of FDG accumulated by cells is a measure of the rate of glycolysis, which reflects cellular activity. As the levels and actions of the neuromodulator adenosine are dynamically regulated by neuronal activity, this study was designed to test whether endogenous adenosine affects tissue accumulation of FDG as assessed by positron emission tomography (PET) or by postmortem analysis of tissue radioactivity. Rats were given an intraperitoneal injection of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropyl‐xanthine (DPCPX, 3 mg/kg), the adenosine kinase inhibitor ABT‐702 (3 mg/kg), or vehicle 10 minutes prior to an intravenous injection of FDG (15.4 ± 0.7 MBq per rat). Rats were then subjected to a 15 minute static PET scan. Reconstructed images were normalized to FDG PET template for rats and standard uptake values (SUVs) were calculated. To examine the regional effect of active treatment compared to vehicle, statistical parametric mapping analysis was performed. Whole‐brain FDG uptake was not affected by drug treatment. Significant regional hypometabolism was detected, particularly in cerebellum, of DPCPX‐ and ABT‐702 treated rats, relative to vehicle‐treated rats. Thus, endogenous adenosine can affect FDG accumulation although this effect is modest in quiescent rats. PMID:27082948

Precision and accuracy of clinical quantification of myocardial blood flow by dynamic PET: A technical perspective.

PubMed

Moody, Jonathan B; Lee, Benjamin C; Corbett, James R; Ficaro, Edward P; Murthy, Venkatesh L

2015-10-01

A number of exciting advances in PET/CT technology and improvements in methodology have recently converged to enhance the feasibility of routine clinical quantification of myocardial blood flow and flow reserve. Recent promising clinical results are pointing toward an important role for myocardial blood flow in the care of patients. Absolute blood flow quantification can be a powerful clinical tool, but its utility will depend on maintaining precision and accuracy in the face of numerous potential sources of methodological errors. Here we review recent data and highlight the impact of PET instrumentation, image reconstruction, and quantification methods, and we emphasize (82)Rb cardiac PET which currently has the widest clinical application. It will be apparent that more data are needed, particularly in relation to newer PET technologies, as well as clinical standardization of PET protocols and methods. We provide recommendations for the methodological factors considered here. At present, myocardial flow reserve appears to be remarkably robust to various methodological errors; however, with greater attention to and more detailed understanding of these sources of error, the clinical benefits of stress-only blood flow measurement may eventually be more fully realized.

New horizons in cardiac innervation imaging: introduction of novel 18F-labeled PET tracers.

PubMed

Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A; Lapa, Constantin; Javadi, Mehrbod S; Higuchi, Takahiro

2017-12-01

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed.

Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.

PubMed

Lake, Spencer T; Greene, Kirsten L; Westphalen, Antonio C; Behr, Spencer C; Zagoria, Ronald; Small, Eric J; Carroll, Peter R; Hope, Thomas A

2017-09-19

PET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68 Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68 Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68 Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared. PSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition. PSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes.

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model.

PubMed

Nie, Xingyu; Laforest, Richard; Elvington, Andrew; Randolph, Gwendalyn J; Zheng, Jie; Voller, Tom; Abendschein, Dana R; Lapi, Suzanne E; Woodard, Pamela K

2016-12-01

The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64 Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0- to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of 64 Cu-ATSM. After 24 h, a 0- to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18 F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 α subunit [HIF-1α]). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. Elevated uptake of 64 Cu-ATSM was found in the rabbits' IF compared with the SF. 64 Cu-ATSM imaging demonstrated IF-to-SF SUV mean ratios (±SD) of 1.75 ± 0.21 and 2.30 ± 0.26 at 4 and 8 wk after injury, respectively. 18 F-FDG imaging demonstrated IF-to-SF SUV mean ratios of 1.84 ± 0.12 at 8 wk after injury. IF-to-BM SUV mean ratios were significantly higher (P < 0.001) than SF-to-BM SUV mean ratios both 4 and 8 wk after injury for 64 Cu-ATSM and 8 wk after injury for 18 F-FDG (P < 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1α. The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that 64 Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer.

PubMed

Sachpekidis, Christos; Bäumer, P; Kopka, K; Hadaschik, B A; Hohenfellner, M; Kopp-Schneider, A; Haberkorn, U; Dimitrakopoulou-Strauss, A

2018-06-01

The aims of this retrospective analysis were to compare 68 Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative 68 Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases. In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with 68 Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05. In total, 168 68 Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both 68 Ga-PSMA PET-positive and CT-positive, 65 were only 68 Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more 68 Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several 68 Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV average and SUV max ), its transport rate from plasma to the interstitial/intracellular compartment (K 1 ), its rate of binding to the PSMA receptor and its internalization (k 3 ), its influx rate (K i ), and its distribution heterogeneity. 68 Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. 68 Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several 68 Ga-PSMA PET parameters.

Quantification of myocardial blood flow with 11C-hydroxyephedrine dynamic PET: comparison with 15O-H2O PET.

PubMed

Hiroshima, Yuji; Manabe, Osamu; Naya, Masanao; Tomiyama, Yuuki; Magota, Keiichi; Obara, Masahiko; Aikawa, Tadao; Oyama-Manabe, Noriko; Yoshinaga, Keiichiro; Hirata, Kenji; Kroenke, Markus; Tamaki, Nagara; Katoh, Chietsugu

2017-12-21

11 C-hydroxyephedrine (HED) PET has been used to evaluate the myocardial sympathetic nervous system (SNS). Here we sought to establish a simultaneous approach for quantifying both myocardial blood flow (MBF) and the SNS from a single HED PET scan. Ten controls and 13 patients with suspected cardiac disease were enrolled. The inflow rate of 11 C-HED (K1) was obtained using a one-tissue-compartment model. We compared this rate with the MBF derived from 15 O-H 2 O PET. In the controls, the relationship between K 1 from 11 C-HED PET and the MBF from 15 O-H 2 O PET was linked by the Renkin-Crone model. The relationship between K 1 from 11 C-HED PET and the MBF from 15 O-H 2 O PET from the controls' data was approximated as follows: K 1   =  (1 - 0.891 * exp(- 0.146/MBF)) * MBF. In the validation set, the correlation coefficient demonstrated a significantly high relationship for both the whole left ventricle (r = 0.95, P < 0.001) and three coronary territories (left anterior descending artery: r = 0.96, left circumflex artery: r = 0.81, right coronary artery: r =  0.86; P < 0.001, respectively). 11 C-HED can simultaneously estimate MBF and sympathetic nervous function without requiring an additional MBF scan for assessing mismatch areas between MBF and SNS.

Feasibility of assessing [(18)F]FDG lung metabolism with late dynamic PET imaging.

PubMed

Laffon, Eric; de Clermont, Henri; Vernejoux, Jean-Marc; Jougon, Jacques; Marthan, Roger

2011-04-01

The aim of this work was to non-invasively establish the feasibility of assessing 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) lung metabolism with the use of a late dynamic positron emission tomograpy (PET) acquisition, i.e., beyond 2 h after injection. The present method has been probed in 11 patients without any respiratory disease, under fasting conditions, by assessing mean values of (18)F-FDG lung metabolism. A kinetic model analysis has been implemented on a simple calculation sheet. An arbitrary (population based) input function has been used in each individual, which was obtained from literature data. In the healthy lung, no (18)F-FDG release was found, and the mean values (±SD) of the (18)F-FDG uptake rate constant and of the fraction of the free tracer in blood and interstitial volume were: K = 0.0016 min(-1) (±0.0005), and F = 0.18 (±0.10), respectively. These results were in very close agreement with literature data that were obtained by both three-compartment model analysis and Patlak graphical analysis (gold standards), and that used an invasive blood sampling. Furthermore, K and the standard uptake value index have been compared. We conclude that assessing lung metabolism of (18)F-FDG in humans with the use of late dynamic PET imaging is feasible. The arbitrary input function of this non-invasive feasibility study could be replaced in further experiments by an input function obtained by arterial sampling. It is suggested that this method may prove useful to quantify (18)F-FDG lung metabolism under pathological conditions.

Anatomically-Aided PET Reconstruction Using the Kernel Method

PubMed Central

Hutchcroft, Will; Wang, Guobao; Chen, Kevin T.; Catana, Ciprian; Qi, Jinyi

2016-01-01

This paper extends the kernel method that was proposed previously for dynamic PET reconstruction, to incorporate anatomical side information into the PET reconstruction model. In contrast to existing methods that incorporate anatomical information using a penalized likelihood framework, the proposed method incorporates this information in the simpler maximum likelihood (ML) formulation and is amenable to ordered subsets. The new method also does not require any segmentation of the anatomical image to obtain edge information. We compare the kernel method with the Bowsher method for anatomically-aided PET image reconstruction through a simulated data set. Computer simulations demonstrate that the kernel method offers advantages over the Bowsher method in region of interest (ROI) quantification. Additionally the kernel method is applied to a 3D patient data set. The kernel method results in reduced noise at a matched contrast level compared with the conventional ML expectation maximization (EM) algorithm. PMID:27541810

Anatomically-aided PET reconstruction using the kernel method.

PubMed

Hutchcroft, Will; Wang, Guobao; Chen, Kevin T; Catana, Ciprian; Qi, Jinyi

2016-09-21

This paper extends the kernel method that was proposed previously for dynamic PET reconstruction, to incorporate anatomical side information into the PET reconstruction model. In contrast to existing methods that incorporate anatomical information using a penalized likelihood framework, the proposed method incorporates this information in the simpler maximum likelihood (ML) formulation and is amenable to ordered subsets. The new method also does not require any segmentation of the anatomical image to obtain edge information. We compare the kernel method with the Bowsher method for anatomically-aided PET image reconstruction through a simulated data set. Computer simulations demonstrate that the kernel method offers advantages over the Bowsher method in region of interest quantification. Additionally the kernel method is applied to a 3D patient data set. The kernel method results in reduced noise at a matched contrast level compared with the conventional ML expectation maximization algorithm.

Anatomically-aided PET reconstruction using the kernel method

NASA Astrophysics Data System (ADS)

Hutchcroft, Will; Wang, Guobao; Chen, Kevin T.; Catana, Ciprian; Qi, Jinyi

2016-09-01

This paper extends the kernel method that was proposed previously for dynamic PET reconstruction, to incorporate anatomical side information into the PET reconstruction model. In contrast to existing methods that incorporate anatomical information using a penalized likelihood framework, the proposed method incorporates this information in the simpler maximum likelihood (ML) formulation and is amenable to ordered subsets. The new method also does not require any segmentation of the anatomical image to obtain edge information. We compare the kernel method with the Bowsher method for anatomically-aided PET image reconstruction through a simulated data set. Computer simulations demonstrate that the kernel method offers advantages over the Bowsher method in region of interest quantification. Additionally the kernel method is applied to a 3D patient data set. The kernel method results in reduced noise at a matched contrast level compared with the conventional ML expectation maximization algorithm.

Retention Kinetics of the 18F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-Hydroxyephedrine and 123I-MIBG.

PubMed

Werner, Rudolf A; Rischpler, Christoph; Onthank, David; Lapa, Constantin; Robinson, Simon; Samnick, Samuel; Javadi, Mehrbod; Schwaiger, Markus; Nekolla, Stephan G; Higuchi, Takahiro

2015-09-01

(18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The (18)F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of (18)F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Healthy New Zealand White rabbits were studied with (18)F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of (18)F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of (11)C-hydroxyephedrine and (123)I-metaiodobenzylguanidine ((123)I-MIBG) was examined by PET and planar scintigraphy, respectively. Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for (11)C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and (18)F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased (11)C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas (18)F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac (123)I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of (18)F-LMI1195, (11)C-hydroxyephedrine, and (123)I-MIBG in rabbit hearts. (11)C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, (18)F-LMI1195 and (123)I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Blood pool and tissue phase patient motion effects on 82rubidium PET myocardial blood flow quantification.

PubMed

Lee, Benjamin C; Moody, Jonathan B; Poitrasson-Rivière, Alexis; Melvin, Amanda C; Weinberg, Richard L; Corbett, James R; Ficaro, Edward P; Murthy, Venkatesh L

2018-03-23

Patient motion can lead to misalignment of left ventricular volumes of interest and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to identify the prevalence of patient motion in both blood and tissue phases and analyze the effects of this motion on MBF and MFR estimates. We selected 225 consecutive patients that underwent dynamic stress/rest rubidium-82 chloride ( 82 Rb) PET imaging. Dynamic image series were iteratively reconstructed with 5- to 10-second frame durations over the first 2 minutes for the blood phase and 10 to 80 seconds for the tissue phase. Motion shifts were assessed by 3 physician readers from the dynamic series and analyzed for frequency, magnitude, time, and direction of motion. The effects of this motion isolated in time, direction, and magnitude on global and regional MBF and MFR estimates were evaluated. Flow estimates derived from the motion corrected images were used as the error references. Mild to moderate motion (5-15 mm) was most prominent in the blood phase in 63% and 44% of the stress and rest studies, respectively. This motion was observed with frequencies of 75% in the septal and inferior directions for stress and 44% in the septal direction for rest. Images with blood phase isolated motion had mean global MBF and MFR errors of 2%-5%. Isolating blood phase motion in the inferior direction resulted in mean MBF and MFR errors of 29%-44% in the RCA territory. Flow errors due to tissue phase isolated motion were within 1%. Patient motion was most prevalent in the blood phase and MBF and MFR errors increased most substantially with motion in the inferior direction. Motion correction focused on these motions is needed to reduce MBF and MFR errors.

Quantification of Dynamic 11C-Phenytoin PET Studies.

PubMed

Mansor, Syahir; Boellaard, Ronald; Froklage, Femke E; Bakker, Esther D M; Yaqub, Maqsood; Voskuyl, Rob A; Schwarte, Lothar A; Verbeek, Joost; Windhorst, Albert D; Lammertsma, Adriaan

2015-09-01

The overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, (11)C-phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of (11)C-phenytoin studies in humans. Dynamic (11)C-phenytoin PET scans of 6 healthy volunteers with arterial sampling were acquired twice on the same day and analyzed using single- and 2-tissue-compartment models with and without a blood volume parameter. Global and regional test-retest (TRT) variability was determined for both plasma to tissue rate constant (K1) and volume of distribution (VT). According to the Akaike information criterion, the reversible single-tissue-compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5% to 16.9% for K1 and from 0.5% to 5.8% for VT. Larger volumes of interest showed better repeatabilities than smaller regions. A 45-min scan provided essentially the same K1 and VT values as a 60-min scan. A reversible single-tissue-compartment model with blood volume seems to be a good candidate model for quantification of dynamic (11)C-phenytoin studies. Scan duration may be reduced to 45 min without notable loss of accuracy and precision of both K1 and VT, although this still needs to be confirmed under pathologic conditions. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Design study of an ultra-compact superconducting cyclotron for isotope production

NASA Astrophysics Data System (ADS)

Smirnov, V.; Vorozhtsov, S.; Vincent, J.

2014-11-01

A 12.5 MeV, 25 μA, proton compact superconducting cyclotron for medical isotope production has been designed and is currently in fabrication. The machine is initially aimed at producing 13N ammonia for Positron Emission Tomography (PET) cardiology applications. With an ultra-compact size and cost-effective price point, this system will offer clinicians unprecedented access to the preferred radiopharmaceutical isotope for cardiac PET imaging. A systems approach that carefully balanced the subsystem requirements coupled to precise beam dynamics calculations was followed. The system is designed to irradiate a liquid target internal to the cyclotron and to minimize the need for radiation shielding. The main parameters of the cyclotron, its design, and principal steps of the development work are presented here.

Positron emission tomography with additional γ-ray detectors for multiple-tracer imaging.

PubMed

Fukuchi, Tomonori; Okauchi, Takashi; Shigeta, Mika; Yamamoto, Seiichi; Watanabe, Yasuyoshi; Enomoto, Shuichi

2017-06-01

Positron emission tomography (PET) is a useful imaging modality that quantifies the physiological distributions of radiolabeled tracers in vivo in humans and animals. However, this technique is unsuitable for multiple-tracer imaging because the annihilation photons used for PET imaging have a fixed energy regardless of the selection of the radionuclide tracer. This study developed a multi-isotope PET (MI-PET) system and evaluated its imaging performance. Our MI-PET system is composed of a PET system and additional γ-ray detectors. The PET system consists of pixelized gadolinium orthosilicate (GSO) scintillation detectors and has a ring geometry that is 95 mm in diameter with an axial field of view of 37.5 mm. The additional detectors are eight bismuth germanium oxide (BGO) scintillation detectors, each of which is 50 × 50 × 30 mm 3 , arranged into two rings mounted on each side of the PET ring with a 92-mm-inner diameter. This system can distinguish between different tracers using the additional γ-ray detectors to observe prompt γ-rays, which are emitted after positron emission and have an energy intrinsic to each radionuclide. Our system can simultaneously acquire double- (two annihilation photons) and triple- (two annihilation photons and a prompt γ-ray) coincidence events. The system's efficiency for detecting prompt de-excitation γ-rays was measured using a positron-γ emitter, 22 Na. Dual-radionuclide ( 18 F and 22 Na) imaging of a rod phantom and a mouse was performed to demonstrate the performance of the developed system. Our system's basic performance was evaluated by reconstructing two images, one containing both tracers and the other containing just the second tracer, from list-mode data sets that were categorized by the presence or absence of the prompt γ-ray. The maximum detection efficiency for 1275 keV γ-rays emitted from 22 Na was approximately 7% at the scanner's center, and the minimum detection efficiency was 5.1% at the edge of the field of view. Dual-radionuclide imaging of the point sources and rod phantom revealed that our system maintained PET's intrinsic spatial resolution and quantitative nature for the second tracer. We also successfully acquired simultaneous double- and triple-coincidence events from a mouse containing 18 F-fluoro-deoxyglucose and 22 Na dissolved in water. The dual-tracer distributions in the mouse obtained by our MI-PET were reasonable from the viewpoints of physiology and pharmacokinetics. This study demonstrates the feasibility of multiple-tracer imaging using PET with additional γ-ray detectors. This method holds promise for enabling the reconstruction of quantitative multiple-tracer images and could be very useful for analyzing multiple-molecular dynamics. © 2017 American Association of Physicists in Medicine.

Preparation and in vivo characterization of 51MnCl2 as PET tracer of Ca2+ channel-mediated transport.

PubMed

Graves, Stephen A; Hernandez, Reinier; Valdovinos, Hector F; Ellison, Paul A; Engle, Jonathan W; Barnhart, Todd E; Cai, Weibo; Nickles, Robert J

2017-06-08

Manganese has long been employed as a T 1 -shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing 52g Mn (t 1/2 : 5.6 d, β + : 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functional β-cell mass quantification. The half-life and confounding gamma emissions of 52g Mn are prohibitive to clinical translation, but the short-lived 51 Mn (t 1/2 : 46 min, β + : 97%) represents a viable alternative. This work develops methods to produce 51 Mn on low-energy medical cyclotrons, characterizes the in vivo behavior of 51 MnCl 2 in mice, and performs preliminary human dosimetry predictions. 51 Mn was produced by proton irradiation of electrodeposited isotopically-enriched 54 Fe targets. Radiochemically isolated 51 MnCl 2 was intravenously administered to ICR mice which were scanned by dynamic and static PET, followed by ex vivo gamma counting. Rapid blood clearance was observed with stable uptake in the pancreas, kidneys, liver, heart, and salivary gland. Dosimetry calculations predict that 370 MBq of 51 Mn in an adult human male would yield an effective dose equivalent of approximately 13.5 mSv, roughly equivalent to a clinical [ 18 F]-FDG procedure.

Feasibility of deep-inspiration breath-hold PET/CT with short-time acquisition: detectability for pulmonary lesions compared with respiratory-gated PET/CT.

PubMed

Yamashita, Shozo; Yokoyama, Kunihiko; Onoguchi, Masahisa; Yamamoto, Haruki; Hiko, Shigeaki; Horita, Akihiro; Nakajima, Kenichi

2014-01-01

Deep-inspiration breath-hold (DIBH) PET/CT with short-time acquisition and respiratory-gated (RG) PET/CT are performed for pulmonary lesions to reduce the respiratory motion artifacts, and to obtain more accurate standardized uptake value (SUV). DIBH PET/CT demonstrates significant advantages in terms of rapid examination, good quality of CT images and low radiation exposure. On the other hand, the image quality of DIBH PET is generally inferior to that of RG PET because of short-time acquisition resulting in poor signal-to-noise ratio. In this study, RG PET has been regarded as a gold standard, and its detectability between DIBH and RG PET studies was compared using each of the most optimal reconstruction parameters. In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were determined. In the clinical study, 19 cases were examined using each of the most optimal reconstruction parameters. In the phantom study, the most optimal reconstruction parameters for DIBH and RG PET were different. Reconstruction parameters of DIBH PET could be obtained by reducing the number of subsets for those of RG PET in the state of fixing the number of iterations. In the clinical study, high correlation in the maximum SUV was observed between DIBH and RG PET studies. The clinical result was consistent with that of the phantom study surrounded by air since most of the lesions were located in the low pulmonary radioactivity. DIBH PET/CT may be the most practical method which can be the first choice to reduce respiratory motion artifacts if the detectability of DIBH PET is equivalent with that of RG PET. Although DIBH PET may have limitations in suboptimal signal-to-noise ratio, most of the lesions surrounded by low background radioactivity could provide nearly equivalent image quality between DIBH and RG PET studies when each of the most optimal reconstruction parameters was used.

Incorporation of MRI-AIF Information For Improved Kinetic Modelling of Dynamic PET Data

NASA Astrophysics Data System (ADS)

Sari, Hasan; Erlandsson, Kjell; Thielemans, Kris; Atkinson, David; Ourselin, Sebastien; Arridge, Simon; Hutton, Brian F.

2015-06-01

In the analysis of dynamic PET data, compartmental kinetic analysis methods require an accurate knowledge of the arterial input function (AIF). Although arterial blood sampling is the gold standard of the methods used to measure the AIF, it is usually not preferred as it is an invasive method. An alternative method is the simultaneous estimation method (SIME), where physiological parameters and the AIF are estimated together, using information from different anatomical regions. Due to the large number of parameters to estimate in its optimisation, SIME is a computationally complex method and may sometimes fail to give accurate estimates. In this work, we try to improve SIME by utilising an input function derived from a simultaneously obtained DSC-MRI scan. With the assumption that the true value of one of the six parameter PET-AIF model can be derived from an MRI-AIF, the method is tested using simulated data. The results indicate that SIME can yield more robust results when the MRI information is included with a significant reduction in absolute bias of Ki estimates.

Myocardial viability assessment with dynamic low-dose iodine-123-iodophenylpentadecanoic acid metabolic imaging: comparison with myocardial biopsy and reinjection SPECT thallium after myocardial infarction.

PubMed

Murray, G L; Schad, N C; Magill, H L; Vander Zwaag, R

1994-04-01

Aggressive cardiac revascularization requires recognition of stunned and hibernating myocardium, and cost considerations may well govern the technique used. Dynamic low-dose (1 mCi) [123I]iodophenylpentadecanoic acid (IPPA) metabolic imaging is a potential alternative to PET using either 18FDG or 15O-water. Resting IPPA images were obtained from patients with severe ischemic cardiomyopathy, and transmural myocardial biopsies were obtained during coronary bypass surgery to confirm viability. Thirty-nine of 43 (91%) biopsies confirmed the results of the IPPA images with a sensitivity for viability of 33/36 (92%) and a specificity of 6/7 (86%). Postoperatively, wall motion improved in 80% of IPPA-viable, dysfunctional segments. Furthermore, when compared to reinjection thallium (SPECT-TI) scans after myocardial infarction, IPPA-SPECT-TI concordance occurred in 27/35 (77%) (K = 0.536, p = 0.0003). Similar to PET, IPPA demonstrated more viability than SPECT-TI, 26/35 (74%) versus 18/35 (51%) (p = 0.047). Metabolic IPPA cardiac viability imaging is a safe, inexpensive technique that may be a useful alternative to PET.

Wavelet-based resolution recovery using an anatomical prior provides quantitative recovery for human population phantom PET [11C]raclopride data

NASA Astrophysics Data System (ADS)

Shidahara, M.; Tsoumpas, C.; McGinnity, C. J.; Kato, T.; Tamura, H.; Hammers, A.; Watabe, H.; Turkheimer, F. E.

2012-05-01

The objective of this study was to evaluate a resolution recovery (RR) method using a variety of simulated human brain [11C]raclopride positron emission tomography (PET) images. Simulated datasets of 15 numerical human phantoms were processed by a wavelet-based RR method using an anatomical prior. The anatomical prior was in the form of a hybrid segmented atlas, which combined an atlas for anatomical labelling and a PET image for functional labelling of each anatomical structure. We applied RR to both 60 min static and dynamic PET images. Recovery was quantified in 84 regions, comparing the typical ‘true’ value for the simulation, as obtained in normal subjects, simulated and RR PET images. The radioactivity concentration in the white matter, striatum and other cortical regions was successfully recovered for the 60 min static image of all 15 human phantoms; the dependence of the solution on accurate anatomical information was demonstrated by the difficulty of the technique to retrieve the subthalamic nuclei due to mismatch between the two atlases used for data simulation and recovery. Structural and functional synergy for resolution recovery (SFS-RR) improved quantification in the caudate and putamen, the main regions of interest, from -30.1% and -26.2% to -17.6% and -15.1%, respectively, for the 60 min static image and from -51.4% and -38.3% to -27.6% and -20.3% for the binding potential (BPND) image, respectively. The proposed methodology proved effective in the RR of small structures from brain [11C]raclopride PET images. The improvement is consistent across the anatomical variability of a simulated population as long as accurate anatomical segmentations are provided.

Triroc: A Multi-Channel SiPM Read-Out ASIC for PET/PET-ToF Application

NASA Astrophysics Data System (ADS)

Ahmad, Salleh; Fleury, Julien; de la Taille, Christophe; Seguin-Moreau, Nathalie; Dulucq, Frederic; Martin-Chassard, Gisele; Callier, Stephane; Thienpont, Damien; Raux, Ludovic

2015-06-01

Triroc is the latest addition to SiPM readout ASICs family developed at Weeroc, a start-up company from the Omega microelectronics group of IN2P3/CNRS. This chip is developed under the framework TRIMAGE European project which is aimed for building a cost effective tri-modal PET/MR/EEG brain scan. To ensure the flexibility and compatibility with any SiPM in the market, the ASIC is designed to be capable of accepting negative and positive polarity input signals. This 64-channel ASIC, is suitable for SiPM readout which requires high accuracy timing and charge measurements. Targeted applications would be PET prototyping with time-of-flight capability. Main features of Triroc includes high dynamic range ADC up to 2500 photoelectrons and TDC fine time binning of 40 ps. Triroc requires very minimal external components which means it is a good contender for compact multichannel PET prototyping. Triroc is designed by using AMS 0.35 μm SiGe technology and it was submitted in March 2014. The detail design of this chip will be presented.

Morphological study of polymer surfaces exposed to non-thermal plasma based on contact angle and the use of scaling laws

NASA Astrophysics Data System (ADS)

Felix, T.; Cassini, F. A.; Benetoli, L. O. B.; Dotto, M. E. R.; Debacher, N. A.

2017-05-01

The experiments presented in this communication have the purpose to elaborate an explanation for the morphological evolution of the growth of polymeric surfaces provided by the treatment of non-thermal plasma. According to the roughness analysis and the model proposed by scaling laws it is possible relate to a predictable or merely random effect. Polyethylene terephthalate (PET) and poly(etherether)ketone (PEEK) samples were exposed to a non-thermal plasma discharge and the resulting surfaces roughness were analyzed based on the measurements from contact angle, scanning electron microscopy and atomic force microscopy coupled with scaling laws analysis which can help to describe and understand the dynamic of formation of a wide variety of rough surfaces. The roughness, RRMS (RMS- Root Mean Square) values for polymer surface range between 19.8 nm and 110.9 nm. The contact angle and the AFM (Atomic Force Microscopy) measurements as a function of the plasma exposure time were in agreement with both polar and dispersive components according to the surface roughness and also with the morphology evaluated described by Wolf-Villain model, with proximate values of α between 0.91(PET) and 0.88(PEEK), β = 0.25(PET) and z = 3,64(PET).

Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET.

PubMed

Mishina, Masahiro; Ishiwata, Kiichi; Kimura, Yuichi; Naganawa, Mika; Oda, Keiichi; Kobayashi, Shiro; Katayama, Yasuo; Ishii, Kenji

2007-09-01

Adenosine A(2A) receptor (A2AR) is thought to interact with dopamine D(2) receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX). We recruited five normal male subjects. A dynamic series of PET scans was performed for 60 min, and the arterial blood was sampled during the scan to measure radioactivity of the parent compound and labeled metabolites. Circular regions of interest of 10-mm diameter were placed in the PET images over the cerebellum, brainstem, thalamus, head of caudate nucleus, anterior and posterior putamen, frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate gyrus for each subject. A two-tissue, three-compartment model was used to estimate K(1), k(2), k(3), and k(4) between metabolite-corrected plasma and tissue time activity of [(11)C]TMSX. The binding potential (BP) was the largest in the anterior (1.25) and posterior putamen (1.20), was next largest in the head of caudate nucleus (1.05) and thalamus (1.03), and was small in the cerebral cortex, especially frontal lobe (0.46). [(11)C]TMSX PET showed the largest BP in the striatum in which A2ARs were enriched as in postmortem and nonhuman studies reported, but that the binding of [(11)C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [(11)C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain.

Gallium-68 EDTA PET/CT for Renal Imaging.

PubMed

Hofman, Michael S; Hicks, Rodney J

2016-09-01

Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 ((68)Ga) EDTA PET usage predates Technetium-99m ((99m)Tc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in (68)Ga owing to the greater availability of PET technology and use of (68)Ga to label other radiotracers. (68)Ga EDTA can be used a substitute for (99m)Tc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the (68)Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed (68)Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for (99m)Tc DTPA if unavailable owing to supply issues, and have additionally examined the role of (68)Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB.

PubMed

Faria, Daniele de Paula; Copray, Sjef; Sijbesma, Jurgen W A; Willemsen, Antoon T M; Buchpiguel, Carlos A; Dierckx, Rudi A J O; de Vries, Erik F J

2014-05-01

In this study, we compared the ability of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake. Sprague-Dawley rats were stereotactically injected with either 1 % lysolecithin or saline into the corpus callosum and striatum of the right brain hemisphere. Dynamic PET imaging with simultaneous arterial blood sampling was performed 7 days after saline injection (control group), 7 days after lysolecithin injection (demyelination group) and 4 weeks after lysolecithin injection (remyelination group). The kinetics of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB was best fitted by Logan graphical analysis, suggesting that tracer binding is reversible. Compartment modelling revealed that all tracers were fitted best with the reversible two-tissue compartment model. Tracer uptake and distribution volume in lesions were in agreement with myelin status. However, the slow kinetics and homogeneous brain uptake of [(11)C]CIC make this tracer less suitable for in vivo PET imaging. [(11)C]PIB showed good uptake in the white matter in the cerebrum, but [(11)C]PIB uptake in the cerebellum was low, despite high myelin density in this region. [(11)C]MeDAS distribution correlated well with myelin density in different brain regions. This study showed that PET imaging of demyelination and remyelination processes in focal lesions is feasible. Our comparison of three myelin tracers showed that [(11)C]MeDAS has more favourable properties for quantitative PET imaging of demyelinated and remyelinated lesions throughout the CNS than [(11)C]CIC and [(11)C]PIB.

The role of necrosis, acute hypoxia and chronic hypoxia in 18F-FMISO PET image contrast: a computational modelling study

NASA Astrophysics Data System (ADS)

Warren, Daniel R.; Partridge, Mike

2016-12-01

Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy dose-painting. However, the relationship between FMISO uptake and oxygen partial pressure ({{P}{{\\text{O}2}}} ) is yet to be quantified fully. Tissue oxygenation varies over distances much smaller than clinical PET resolution (<100 μm versus  ˜4 mm), and cyclic variations in tumour perfusion have been observed on timescales shorter than typical FMISO PET studies (˜20 min versus a few hours). Furthermore, tracer uptake may be decreased in voxels containing some degree of necrosis. This work develops a computational model of FMISO uptake in millimetre-scale tumour regions. Coupled partial differential equations govern the evolution of oxygen and FMISO distributions, and a dynamic vascular source map represents temporal variations in perfusion. Local FMISO binding capacity is modulated by the necrotic fraction. Outputs include spatiotemporal maps of {{P}{{\\text{O}2}}} and tracer accumulation, enabling calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a function of mean tissue oxygenation. The model is characterised using experimental data, finding half-maximal FMISO binding at local {{P}{{\\text{O}2}}} of 1.4 mmHg (95% CI: 0.3-2.6 mmHg) and half-maximal necrosis at 1.2 mmHg (0.1-4.9 mmHg). Simulations predict a non-linear non-monotonic relationship between FMISO activity (4 hr post-injection) and mean tissue {{P}{{\\text{O}2}}} : tracer uptake rises sharply from negligible levels in avascular tissue, peaking at  ˜5 mmHg and declining towards blood activity in well-oxygenated conditions. Greater temporal variation in perfusion increases peak TBRs (range 2.20-5.27) as a result of smaller predicted necrotic fraction, rather than fundamental differences in FMISO accumulation under acute hypoxia. Identical late FMISO uptake can occur in regions with differing {{P}{{\\text{O}2}}} and necrotic fraction, but simulated TACs indicate that additional early-phase information may allow discrimination of hypoxic and necrotic signals. We conclude that a robust approach to FMISO interpretation (and dose-painting prescription) is likely to be based on dynamic PET analysis.

Single-scan dual-tracer FLT+FDG PET tumor characterization.

PubMed

Kadrmas, Dan J; Rust, Thomas C; Hoffman, John M

2013-02-07

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems--both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), K(net), and K(1) as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k(2), k(3)) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.

Single-scan dual-tracer FLT+FDG PET tumor characterization

NASA Astrophysics Data System (ADS)

Kadrmas, Dan J.; Rust, Thomas C.; Hoffman, John M.

2013-02-01

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10-60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging.

Single-scan dual-tracer FLT+FDG PET tumor characterization

PubMed Central

Kadrmas, Dan J; Rust, Thomas C; Hoffman, John M

2013-01-01

Rapid multi-tracer PET aims to image two or more tracers in a single scan, simultaneously characterizing multiple aspects of physiology and function without the need for repeat imaging visits. Using dynamic imaging with staggered injections, constraints on the kinetic behavior of each tracer are applied to recover individual-tracer measures from the multi-tracer PET signal. The ability to rapidly and reliably image both 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) would provide complementary measures of tumor metabolism and proliferative activity, with important applications in guiding oncologic treatment decisions and assessing response. However, this tracer combination presents one of the most challenging dual-tracer signal-separation problems—both tracers have the same radioactive half-life, and the injection delay is short relative to the half-life and tracer kinetics. This work investigates techniques for single-scan dual-tracer FLT+FDG PET tumor imaging, characterizing the performance of recovering static and dynamic imaging measures for each tracer from dual-tracer datasets. Simulation studies were performed to characterize dual-tracer signal-separation performance for imaging protocols with both injection orders and injection delays of 10–60 min. Better performance was observed when FLT was administered first, and longer delays before administration of FDG provided more robust signal-separation and recovery of the single-tracer imaging measures. An injection delay of 30 min led to good recovery (R > 0.96) of static image values (e.g. SUV), Knet, and K1 as compared to values from separate, single-tracer time-activity curves. Recovery of higher order rate parameters (k2, k3) was less robust, indicating that information regarding these parameters was harder to recover in the presence of statistical noise and dual-tracer effects. Performance of the dual-tracer FLT(0 min)+FDG(32 min) technique was further evaluated using PET/CT imaging studies in five patients with primary brain tumors where the data from separate scans of each tracer were combined to synthesize dual-tracer scans with known single-tracer components; results demonstrated similar dual-tracer signal recovery performance. We conclude that rapid dual-tracer FLT+FDG tumor imaging is feasible and can provide quantitative tumor imaging measures comparable to those from conventional separate-scan imaging. PMID:23296314

The role of necrosis, acute hypoxia and chronic hypoxia in 18F-FMISO PET image contrast: a computational modelling study.

PubMed

Warren, Daniel R; Partridge, Mike

2016-12-21

Positron emission tomography (PET) using 18 F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy dose-painting. However, the relationship between FMISO uptake and oxygen partial pressure ([Formula: see text]) is yet to be quantified fully. Tissue oxygenation varies over distances much smaller than clinical PET resolution (<100 μm versus  ∼4 mm), and cyclic variations in tumour perfusion have been observed on timescales shorter than typical FMISO PET studies (∼20 min versus a few hours). Furthermore, tracer uptake may be decreased in voxels containing some degree of necrosis. This work develops a computational model of FMISO uptake in millimetre-scale tumour regions. Coupled partial differential equations govern the evolution of oxygen and FMISO distributions, and a dynamic vascular source map represents temporal variations in perfusion. Local FMISO binding capacity is modulated by the necrotic fraction. Outputs include spatiotemporal maps of [Formula: see text] and tracer accumulation, enabling calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a function of mean tissue oxygenation. The model is characterised using experimental data, finding half-maximal FMISO binding at local [Formula: see text] of 1.4 mmHg (95% CI: 0.3-2.6 mmHg) and half-maximal necrosis at 1.2 mmHg (0.1-4.9 mmHg). Simulations predict a non-linear non-monotonic relationship between FMISO activity (4 hr post-injection) and mean tissue [Formula: see text] : tracer uptake rises sharply from negligible levels in avascular tissue, peaking at  ∼5 mmHg and declining towards blood activity in well-oxygenated conditions. Greater temporal variation in perfusion increases peak TBRs (range 2.20-5.27) as a result of smaller predicted necrotic fraction, rather than fundamental differences in FMISO accumulation under acute hypoxia. Identical late FMISO uptake can occur in regions with differing [Formula: see text] and necrotic fraction, but simulated TACs indicate that additional early-phase information may allow discrimination of hypoxic and necrotic signals. We conclude that a robust approach to FMISO interpretation (and dose-painting prescription) is likely to be based on dynamic PET analysis.

Automatic lesion detection and segmentation of 18F-FET PET in gliomas: A full 3D U-Net convolutional neural network study.

PubMed

Blanc-Durand, Paul; Van Der Gucht, Axel; Schaefer, Niklaus; Itti, Emmanuel; Prior, John O

2018-01-01

Amino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN). All dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation. Thirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%]. With relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.

Dynamic contrast-enhanced MRI versus 18F-FDG PET/CT: Which is better in differentiation between malignant and benign solitary pulmonary nodules?

PubMed

Feng, Feng; Qiang, Fulin; Shen, Aijun; Shi, Donghui; Fu, Aiyan; Li, Haiming; Zhang, Mingzhu; Xia, Ganlin; Cao, Peng

2018-02-01

To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) with that of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in the differentiation of malignant and benign solitary pulmonary nodules (SPNs). Forty-nine patients with SPNs were included in this prospective study. Thirty-two of the patients had malignant SPNs, while the other 17 had benign SPNs. All these patients underwent DCE-MRI and 18 F-FDG PET/CT examinations. The quantitative MRI pharmacokinetic parameters, including the trans-endothelial transfer constant (K trans ), redistribution rate constant (K ep ), and fractional volume (V e ), were calculated using the Extended-Tofts Linear two-compartment model. The 18 F-FDG PET/CT parameter, maximum standardized uptake value (SUV max ), was also measured. Spearman's correlations were calculated between the MRI pharmacokinetic parameters and the SUV max of each SPN. These parameters were statistically compared between the malignant and benign nodules. Receiver operating characteristic (ROC) analyses were used to compare the diagnostic capability between the DCE-MRI and 18 F-FDG PET/CT indexes. Positive correlations were found between K trans and SUV max , and between K ep and SUV max (P<0.05). There were significant differences between the malignant and benign nodules in terms of the K trans , K ep and SUV max values (P<0.05). The areas under the ROC curve (AUC) of K trans , K ep and SUV max between the malignant and benign nodules were 0.909, 0.838 and 0.759, respectively. The sensitivity and specificity in differentiating malignant from benign SPNs were 90.6% and 82.4% for K trans ; 87.5% and 76.5% for K ep ; and 75.0% and 70.6% for SUV max , respectively. The sensitivity and specificity of K trans and K ep were higher than those of SUV max , but there was no significant difference between them (P>0.05). DCE-MRI can be used to differentiate between benign and malignant SPNs and has the advantage of being radiation free.

Dynamic contrast-enhanced MRI versus 18F-FDG PET/CT: Which is better in differentiation between malignant and benign solitary pulmonary nodules?

PubMed Central

Feng, Feng; Qiang, Fulin; Shen, Aijun; Shi, Donghui; Fu, Aiyan; Li, Haiming; Zhang, Mingzhu; Xia, Ganlin; Cao, Peng

2018-01-01

Objective To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) with that of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the differentiation of malignant and benign solitary pulmonary nodules (SPNs). Methods Forty-nine patients with SPNs were included in this prospective study. Thirty-two of the patients had malignant SPNs, while the other 17 had benign SPNs. All these patients underwent DCE-MRI and 18F-FDG PET/CT examinations. The quantitative MRI pharmacokinetic parameters, including the trans-endothelial transfer constant (Ktrans), redistribution rate constant (Kep), and fractional volume (Ve), were calculated using the Extended-Tofts Linear two-compartment model. The 18F-FDG PET/CT parameter, maximum standardized uptake value (SUVmax), was also measured. Spearman’s correlations were calculated between the MRI pharmacokinetic parameters and the SUVmax of each SPN. These parameters were statistically compared between the malignant and benign nodules. Receiver operating characteristic (ROC) analyses were used to compare the diagnostic capability between the DCE-MRI and 18F-FDG PET/CT indexes. Results Positive correlations were found between Ktrans and SUVmax, and between Kep and SUVmax (P<0.05). There were significant differences between the malignant and benign nodules in terms of the Ktrans, Kep and SUVmax values (P<0.05). The areas under the ROC curve (AUC) of Ktrans, Kep and SUVmax between the malignant and benign nodules were 0.909, 0.838 and 0.759, respectively. The sensitivity and specificity in differentiating malignant from benign SPNs were 90.6% and 82.4% for Ktrans; 87.5% and 76.5% for Kep; and 75.0% and 70.6% for SUVmax, respectively. The sensitivity and specificity of Ktrans and Kep were higher than those of SUVmax, but there was no significant difference between them (P>0.05). Conclusions DCE-MRI can be used to differentiate between benign and malignant SPNs and has the advantage of being radiation free. PMID:29545716

WE-H-207A-06: Hypoxia Quantification in Static PET Images: The Signal in the Noise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, H; Yeung, I; Milosevic, M

2016-06-15

Purpose: Quantification of hypoxia from PET images is of considerable clinical interest. In the absence of dynamic PET imaging the hypoxic fraction (HF) of a tumor has to be estimated from voxel values of activity concentration of a radioactive hypoxia tracer. This work is part of an effort to standardize quantification of tumor hypoxic fraction from PET images. Methods: A simple hypoxia imaging model in the tumor was developed. The distribution of the tracer activity was described as the sum of two different probability distributions, one for the normoxic (and necrotic), the other for the hypoxic voxels. The widths ofmore » the distributions arise due to variability of the transport, tumor tissue inhomogeneity, tracer binding kinetics, and due to PET image noise. Quantification of HF was performed for various levels of variability using two different methodologies: a) classification thresholds between normoxic and hypoxic voxels based on a non-hypoxic surrogate (muscle), and b) estimation of the (posterior) probability distributions based on maximizing likelihood optimization that does not require a surrogate. Data from the hypoxia imaging model and from 27 cervical cancer patients enrolled in a FAZA PET study were analyzed. Results: In the model, where the true value of HF is known, thresholds usually underestimate the value for large variability. For the patients, a significant uncertainty of the HF values (an average intra-patient range of 17%) was caused by spatial non-uniformity of image noise which is a hallmark of all PET images. Maximum likelihood estimation (MLE) is able to directly optimize for the weights of both distributions, however, may suffer from poor optimization convergence. For some patients, MLE-based HF values showed significant differences to threshold-based HF-values. Conclusion: HF-values depend critically on the magnitude of the different sources of tracer uptake variability. A measure of confidence should also be reported.« less

Covalent dye attachment influences the dynamics and conformational properties of flexible peptides

PubMed Central

Crevenna, Alvaro H.; Bomblies, Rainer; Lamb, Don C.

2017-01-01

Fluorescence spectroscopy techniques like Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS) have become important tools for the in vitro and in vivo investigation of conformational dynamics in biomolecules. These methods rely on the distance-dependent quenching of the fluorescence signal of a donor fluorophore either by a fluorescent acceptor fluorophore (FRET) or a non-fluorescent quencher, as used in FCS with photoinduced electron transfer (PET). The attachment of fluorophores to the molecule of interest can potentially alter the molecular properties and may affect the relevant conformational states and dynamics especially of flexible biomolecules like intrinsically disordered proteins (IDP). Using the intrinsically disordered S-peptide as a model system, we investigate the impact of terminal fluorescence labeling on the molecular properties. We perform extensive molecular dynamics simulations on the labeled and unlabeled peptide and compare the results with in vitro PET-FCS measurements. Experimental and simulated timescales of end-to-end fluctuations were found in excellent agreement. Comparison between simulations with and without labels reveal that the π-stacking interaction between the fluorophore labels traps the conformation of S-peptide in a single dominant state, while the unlabeled peptide undergoes continuous conformational rearrangements. Furthermore, we find that the open to closed transition rate of S-peptide is decreased by at least one order of magnitude by the fluorophore attachment. Our approach combining experimental and in silico methods provides a benchmark for the simulations and reveals the significant effect that fluorescence labeling can have on the conformational dynamics of small biomolecules, at least for inherently flexible short peptides. The presented protocol is not only useful for comparing PET-FCS experiments with simulation results but provides a strategy to minimize the influence on molecular properties when chosing labeling positions for fluorescence experiments. PMID:28542243

Long-term potential and actual evapotranspiration of two different forests on the Atlantic Coastal Plain

Treesearch

Devendra Amatya; S. Tian; Z. Dai; Ge Sun

2016-01-01

A reliable estimate of potential evapotranspiration (PET) for a forest ecosystem is critical in ecohydrologic modeling related with water supply, vegetation dynamics, and climate change and yet is a challenging task due to its complexity. Based on long-term on-site measured hydro-climatic data and predictions from earlier validated hydrologic modeling studies...

Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study.

PubMed

Brendel, Matthias; Probst, Federico; Jaworska, Anna; Overhoff, Felix; Korzhova, Viktoria; Albert, Nathalie L; Beck, Roswitha; Lindner, Simon; Gildehaus, Franz-Josef; Baumann, Karlheinz; Bartenstein, Peter; Kleinberger, Gernot; Haass, Christian; Herms, Jochen; Rominger, Axel

2016-06-01

Amyloid imaging by small-animal PET in models of Alzheimer disease (AD) offers the possibility to track amyloidogenesis and brain energy metabolism. Because microglial activation is thought to contribute to AD pathology, we undertook a triple-tracer small-animal PET study to assess microglial activation and glucose metabolism in association with amyloid plaque load in a transgenic AD mouse model. Groups of PS2APP and C57BL/6 wild-type mice of various ages were examined by small-animal PET. We acquired 90-min dynamic emission data with (18)F-GE180 for imaging activated microglia (18-kD translocator protein ligand [TSPO]) and static 30- to 60-min recordings with (18)F-FDG for energy metabolism and (18)F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic nonlinear spatial normalization, and SUVRs were calculated. For the novel TSPO tracer (18)F-GE180, we then calculated distribution volume ratios after establishing a suitable reference region. Immunohistochemical analyses with TSPO antisera, methoxy-X04 staining for fibrillary β-amyloid, and ex vivo autoradiography served as terminal gold standard assessments. SUVR at 60-90 min after injection gave robust quantitation of (18)F-GE180, which correlated well with distribution volume ratios calculated from the entire recording and using a white matter reference region. Relative to age-matched wild-type, (18)F-GE180 SUVR was slightly elevated in PS2APP mice at 5 mo (+9%; P < 0.01) and distinctly increased at 16 mo (+25%; P < 0.001). Over this age range, there was a high positive correlation between small-animal PET findings of microglial activation with amyloid load (R = 0.85; P < 0.001) and likewise with metabolism (R = 0.61; P < 0.005). Immunohistochemical and autoradiographic findings confirmed the in vivo small-animal PET data. In this first triple-tracer small-animal PET in a well-established AD mouse model, we found evidence for age-dependent microglial activation. This activation, correlating positively with the amyloid load, implies a relationship between amyloidosis and inflammation in the PS2APP AD mouse model. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules—the SPUtNIk study

PubMed Central

Qureshi, N R; Rintoul, R C; Miles, K A; George, S; Harris, S; Madden, J; Cozens, K; Little, L A; Eichhorst, K; Jones, J; Moate, P; McClement, C; Pike, L; Sinclair, D; Wong, W L; Shekhdar, J; Eaton, R; Shah, A; Brindle, L; Peebles, C; Banerjee, A; Dizdarevic, S; Han, S; Poon, F W; Groves, A M; Kurban, L; Frew, A J; Callister, M E; Crosbie, P; Gleeson, F V; Karunasaagarar, K; Kankam, O; Gilbert, F J

2016-01-01

Introduction Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. Methods and analysis The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. Ethics and dissemination Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. Trial registration number ISRCTN30784948; Pre-results. PMID:27843550

Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment.

PubMed

Tateishi, Ukihide; Miyake, Mototaka; Nagaoka, Tomoaki; Terauchi, Takashi; Kubota, Kazunori; Kinoshita, Takayuki; Daisaki, Hiromitsu; Macapinlac, Homer A

2012-04-01

To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P < .0001), percentage rate constant (%k(ep)) (OR, 1.07; CI: 1.03, 1.12; P = .002), and percentage area under the time-intensity curve over 90 seconds (%AUC(90)) (OR, 1.04; CI: 1.01, 1.07; P = .048). When diagnostic accuracies are compared, PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ(ep) [83.8%] or %AUC(90) [76.8%]; P < .05). The sensitivities of %SUV(max) (66.7%), %k(ep) (51.7%), and %AUC(90) (50.0%) at (18)F-FDG PET/CT and DCE MR after two cycles of NAC are not acceptable, but the specificities (96.4%, 92.0%, and 95.2%, respectively) are high for stratification of pCR cases in breast cancer. © RSNA, 2012.

Estimation of arterial input by a noninvasive image derived method in brain H2 15O PET study: confirmation of arterial location using MR angiography

NASA Astrophysics Data System (ADS)

Muinul Islam, Muhammad; Tsujikawa, Tetsuya; Mori, Tetsuya; Kiyono, Yasushi; Okazawa, Hidehiko

2017-06-01

A noninvasive method to estimate input function directly from H2 15O brain PET data for measurement of cerebral blood flow (CBF) was proposed in this study. The image derived input function (IDIF) method extracted the time-activity curves (TAC) of the major cerebral arteries at the skull base from the dynamic PET data. The extracted primordial IDIF showed almost the same radioactivity as the arterial input function (AIF) from sampled blood at the plateau part in the later phase, but significantly lower radioactivity in the initial arterial phase compared with that of AIF-TAC. To correct the initial part of the IDIF, a dispersion function was applied and two constants for the correction were determined by fitting with the individual AIF in 15 patients with unilateral arterial stenoocclusive lesions. The area under the curves (AUC) from the two input functions showed good agreement with the mean AUCIDIF/AUCAIF ratio of 0.92  ±  0.09. The final products of CBF and arterial-to-capillary vascular volume (V 0) obtained from the IDIF and AIF showed no difference, and had with high correlation coefficients.

Motion compensation for fully 4D PET reconstruction using PET superset data

NASA Astrophysics Data System (ADS)

Verhaeghe, J.; Gravel, P.; Mio, R.; Fukasawa, R.; Rosa-Neto, P.; Soucy, J.-P.; Thompson, C. J.; Reader, A. J.

2010-07-01

Fully 4D PET image reconstruction is receiving increasing research interest due to its ability to significantly reduce spatiotemporal noise in dynamic PET imaging. However, thus far in the literature, the important issue of correcting for subject head motion has not been considered. Specifically, as a direct consequence of using temporally extensive basis functions, a single instance of movement propagates to impair the reconstruction of multiple time frames, even if no further movement occurs in those frames. Existing 3D motion compensation strategies have not yet been adapted to 4D reconstruction, and as such the benefits of 4D algorithms have not yet been reaped in a clinical setting where head movement undoubtedly occurs. This work addresses this need, developing a motion compensation method suitable for fully 4D reconstruction methods which exploits an optical tracking system to measure the head motion along with PET superset data to store the motion compensated data. List-mode events are histogrammed as PET superset data according to the measured motion, and a specially devised normalization scheme for motion compensated reconstruction from the superset data is required. This work proceeds to propose the corresponding time-dependent normalization modifications which are required for a major class of fully 4D image reconstruction algorithms (those which use linear combinations of temporal basis functions). Using realistically simulated as well as real high-resolution PET data from the HRRT, we demonstrate both the detrimental impact of subject head motion in fully 4D PET reconstruction and the efficacy of our proposed modifications to 4D algorithms. Benefits are shown both for the individual PET image frames as well as for parametric images of tracer uptake and volume of distribution for 18F-FDG obtained from Patlak analysis.

Toughening modification of poly(butylene terephthalate)/poly(ethylene terephthalate) blends by an epoxy-functionalized elastomer

NASA Astrophysics Data System (ADS)

Zhang, Weizhou; Wang, Kai; Yan, Wei; Guo, Weihong

2017-10-01

New toughened poly(butylene terephthalate) (PBT)/poly(ethylene terephthalate) (PET) (40/60 wt%) blends were obtained by melting with Glycidyl methacrylate grafted poly(ethylene octane) copolymer (POE-g-GMA), varying the POE-g-GMA content up to 20 wt%, in a twin-screw extruder, followed by injection molding. The influence of POE-g-GMA on the properties of the PBT/PET blends was investigated by mechanical testing, Fourier transform infrared (FT-IR) analysis, gel fractions analysis, dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC) and scanning electronic microscopy (SEM). The mechanical testing results indicated that the incorporation of POE-g-GMA led to increases in the notched impact strength and decreases in the tensile strength, flexural strength, and flexural modulus. When POE-g-GMA content reached 20 wt%, the notched impact strength (8.0 kJ m-2) was achieved for the PBT/PET/POE-g-GMA blends. FT-IR results proved that some PBT/PET/POE-g-GMA copolymers were produced, which improved the compatibility between POE-g-GMA and the PBT/PET matrix. The extent of crosslinking was observed by gel fraction measurements. DMA results further testified chain-extending and micro-crosslink reactions occurred between POE-g-GMA and PBT/PET blends. In addition, the reactions induced by POE-g-GMA affected the crystallization behavior of PBT/PET blends obviously, as observed from DSC results. By means of SEM observation of the impact fracture surface morphology, and the discussion of the micro-crosslink reaction process between the epoxide-containing elastomers and PBT/PET matrix, the toughening mechanism was proposed to be taken into account the shear yielding of PBT/PET matrix and cavitation of elastomer particles.

Motion compensation for fully 4D PET reconstruction using PET superset data.

PubMed

Verhaeghe, J; Gravel, P; Mio, R; Fukasawa, R; Rosa-Neto, P; Soucy, J-P; Thompson, C J; Reader, A J

2010-07-21

Fully 4D PET image reconstruction is receiving increasing research interest due to its ability to significantly reduce spatiotemporal noise in dynamic PET imaging. However, thus far in the literature, the important issue of correcting for subject head motion has not been considered. Specifically, as a direct consequence of using temporally extensive basis functions, a single instance of movement propagates to impair the reconstruction of multiple time frames, even if no further movement occurs in those frames. Existing 3D motion compensation strategies have not yet been adapted to 4D reconstruction, and as such the benefits of 4D algorithms have not yet been reaped in a clinical setting where head movement undoubtedly occurs. This work addresses this need, developing a motion compensation method suitable for fully 4D reconstruction methods which exploits an optical tracking system to measure the head motion along with PET superset data to store the motion compensated data. List-mode events are histogrammed as PET superset data according to the measured motion, and a specially devised normalization scheme for motion compensated reconstruction from the superset data is required. This work proceeds to propose the corresponding time-dependent normalization modifications which are required for a major class of fully 4D image reconstruction algorithms (those which use linear combinations of temporal basis functions). Using realistically simulated as well as real high-resolution PET data from the HRRT, we demonstrate both the detrimental impact of subject head motion in fully 4D PET reconstruction and the efficacy of our proposed modifications to 4D algorithms. Benefits are shown both for the individual PET image frames as well as for parametric images of tracer uptake and volume of distribution for (18)F-FDG obtained from Patlak analysis.

Rapid Multi-Tracer PET Tumor Imaging With F-FDG and Secondary Shorter-Lived Tracers.

PubMed

Black, Noel F; McJames, Scott; Kadrmas, Dan J

2009-10-01

Rapid multi-tracer PET, where two to three PET tracers are rapidly scanned with staggered injections, can recover certain imaging measures for each tracer based on differences in tracer kinetics and decay. We previously showed that single-tracer imaging measures can be recovered to a certain extent from rapid dual-tracer (62)Cu - PTSM (blood flow) + (62)Cu - ATSM (hypoxia) tumor imaging. In this work, the feasibility of rapidly imaging (18)F-FDG plus one or two of these shorter-lived secondary tracers was evaluated in the same tumor model. Dynamic PET imaging was performed in four dogs with pre-existing tumors, and the raw scan data was combined to emulate 60 minute long dual- and triple-tracer scans, using the single-tracer scans as gold standards. The multi-tracer data were processed for static (SUV) and kinetic (K(1), K(net)) endpoints for each tracer, followed by linear regression analysis of multi-tracer versus single-tracer results. Static and quantitative dynamic imaging measures of FDG were both accurately recovered from the multi-tracer scans, closely matching the single-tracer FDG standards (R > 0.99). Quantitative blood flow information, as measured by PTSM K(1) and SUV, was also accurately recovered from the multi-tracer scans (R = 0.97). Recovery of ATSM kinetic parameters proved more difficult, though the ATSM SUV was reasonably well recovered (R = 0.92). We conclude that certain additional information from one to two shorter-lived PET tracers may be measured in a rapid multi-tracer scan alongside FDG without compromising the assessment of glucose metabolism. Such additional and complementary information has the potential to improve tumor characterization in vivo, warranting further investigation of rapid multi-tracer techniques.

Rapid Multi-Tracer PET Tumor Imaging With 18F-FDG and Secondary Shorter-Lived Tracers

PubMed Central

Black, Noel F.; McJames, Scott; Kadrmas, Dan J.

2009-01-01

Rapid multi-tracer PET, where two to three PET tracers are rapidly scanned with staggered injections, can recover certain imaging measures for each tracer based on differences in tracer kinetics and decay. We previously showed that single-tracer imaging measures can be recovered to a certain extent from rapid dual-tracer 62Cu – PTSM (blood flow) + 62Cu — ATSM (hypoxia) tumor imaging. In this work, the feasibility of rapidly imaging 18F-FDG plus one or two of these shorter-lived secondary tracers was evaluated in the same tumor model. Dynamic PET imaging was performed in four dogs with pre-existing tumors, and the raw scan data was combined to emulate 60 minute long dual- and triple-tracer scans, using the single-tracer scans as gold standards. The multi-tracer data were processed for static (SUV) and kinetic (K1, Knet) endpoints for each tracer, followed by linear regression analysis of multi-tracer versus single-tracer results. Static and quantitative dynamic imaging measures of FDG were both accurately recovered from the multi-tracer scans, closely matching the single-tracer FDG standards (R > 0.99). Quantitative blood flow information, as measured by PTSM K1 and SUV, was also accurately recovered from the multi-tracer scans (R = 0.97). Recovery of ATSM kinetic parameters proved more difficult, though the ATSM SUV was reasonably well recovered (R = 0.92). We conclude that certain additional information from one to two shorter-lived PET tracers may be measured in a rapid multi-tracer scan alongside FDG without compromising the assessment of glucose metabolism. Such additional and complementary information has the potential to improve tumor characterization in vivo, warranting further investigation of rapid multi-tracer techniques. PMID:20046800

A Registration Method Based on Contour Point Cloud for 3D Whole-Body PET and CT Images

PubMed Central

Yang, Qiyao; Wang, Zhiguo; Zhang, Guoxu

2017-01-01

The PET and CT fusion image, combining the anatomical and functional information, has important clinical meaning. An effective registration of PET and CT images is the basis of image fusion. This paper presents a multithread registration method based on contour point cloud for 3D whole-body PET and CT images. Firstly, a geometric feature-based segmentation (GFS) method and a dynamic threshold denoising (DTD) method are creatively proposed to preprocess CT and PET images, respectively. Next, a new automated trunk slices extraction method is presented for extracting feature point clouds. Finally, the multithread Iterative Closet Point is adopted to drive an affine transform. We compare our method with a multiresolution registration method based on Mattes Mutual Information on 13 pairs (246~286 slices per pair) of 3D whole-body PET and CT data. Experimental results demonstrate the registration effectiveness of our method with lower negative normalization correlation (NC = −0.933) on feature images and less Euclidean distance error (ED = 2.826) on landmark points, outperforming the source data (NC = −0.496, ED = 25.847) and the compared method (NC = −0.614, ED = 16.085). Moreover, our method is about ten times faster than the compared one. PMID:28316979

Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

PubMed

Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P; Popota, Foteini; Fernández-Soriano, Francisco J; Planas, Anna M; Gispert, Juan D

2011-06-01

[¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹⁸F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. Elevated uptake of ¹⁸F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹⁸F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Y.; Hawkins, R.A.; Huang, S.C.

The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. Twenty studies were performed on 10 normal volunteers (ages 24 {+-} 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph.more » A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K{sub 1}, increased significantly (p < 0.05) from 0.864 {+-} 0.136 ml/min/g in fasting studies to 1.058 {+-} 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k{sub 3}, from 0.005 {+-} 0.003 min{sup -1} in fasting studies to 0.013 {+-} 0.007 min{sup -1} in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k{sub 3}/(k{sub 2} + k{sub 3})) and the influx constant (K{sub 1}k{sub 3}/(k{sub 2} + k{sub 3})). No significant differences in the liver-to-plasma transport rate constant, k{sub 2}, dephosphorylation constant, k{sub 4}, or distribution volume of FDG (K{sub 1}/(k{sub 2} + k{sub 3})) were observed. Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast. 22 refs., 2 figs., 3 tabs.« less

Kinetic quantitation of cerebral PET-FDG studies without concurrent blood sampling: statistical recovery of the arterial input function.

PubMed

O'Sullivan, F; Kirrane, J; Muzi, M; O'Sullivan, J N; Spence, A M; Mankoff, D A; Krohn, K A

2010-03-01

Kinetic quantitation of dynamic positron emission tomography (PET) studies via compartmental modeling usually requires the time-course of the radio-tracer concentration in the arterial blood as an arterial input function (AIF). For human and animal imaging applications, significant practical difficulties are associated with direct arterial sampling and as a result there is substantial interest in alternative methods that require no blood sampling at the time of the study. A fixed population template input function derived from prior experience with directly sampled arterial curves is one possibility. Image-based extraction, including requisite adjustment for spillover and recovery, is another approach. The present work considers a hybrid statistical approach based on a penalty formulation in which the information derived from a priori studies is combined in a Bayesian manner with information contained in the sampled image data in order to obtain an input function estimate. The absolute scaling of the input is achieved by an empirical calibration equation involving the injected dose together with the subject's weight, height and gender. The technique is illustrated in the context of (18)F -Fluorodeoxyglucose (FDG) PET studies in humans. A collection of 79 arterially sampled FDG blood curves are used as a basis for a priori characterization of input function variability, including scaling characteristics. Data from a series of 12 dynamic cerebral FDG PET studies in normal subjects are used to evaluate the performance of the penalty-based AIF estimation technique. The focus of evaluations is on quantitation of FDG kinetics over a set of 10 regional brain structures. As well as the new method, a fixed population template AIF and a direct AIF estimate based on segmentation are also considered. Kinetics analyses resulting from these three AIFs are compared with those resulting from radially sampled AIFs. The proposed penalty-based AIF extraction method is found to achieve significant improvements over the fixed template and the segmentation methods. As well as achieving acceptable kinetic parameter accuracy, the quality of fit of the region of interest (ROI) time-course data based on the extracted AIF, matches results based on arterially sampled AIFs. In comparison, significant deviation in the estimation of FDG flux and degradation in ROI data fit are found with the template and segmentation methods. The proposed AIF extraction method is recommended for practical use.

An algorithm for longitudinal registration of PET/CT images acquired during neoadjuvant chemotherapy in breast cancer: preliminary results.

PubMed

Li, Xia; Abramson, Richard G; Arlinghaus, Lori R; Chakravarthy, Anuradha Bapsi; Abramson, Vandana; Mayer, Ingrid; Farley, Jaime; Delbeke, Dominique; Yankeelov, Thomas E

2012-11-16

By providing estimates of tumor glucose metabolism, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can potentially characterize the response of breast tumors to treatment. To assess therapy response, serial measurements of FDG-PET parameters (derived from static and/or dynamic images) can be obtained at different time points during the course of treatment. However, most studies track the changes in average parameter values obtained from the whole tumor, thereby discarding all spatial information manifested in tumor heterogeneity. Here, we propose a method whereby serially acquired FDG-PET breast data sets can be spatially co-registered to enable the spatial comparison of parameter maps at the voxel level. The goal is to optimally register normal tissues while simultaneously preventing tumor distortion. In order to accomplish this, we constructed a PET support device to enable PET/CT imaging of the breasts of ten patients in the prone position and applied a mutual information-based rigid body registration followed by a non-rigid registration. The non-rigid registration algorithm extended the adaptive bases algorithm (ABA) by incorporating a tumor volume-preserving constraint, which computed the Jacobian determinant over the tumor regions as outlined on the PET/CT images, into the cost function. We tested this approach on ten breast cancer patients undergoing neoadjuvant chemotherapy. By both qualitative and quantitative evaluation, our constrained algorithm yielded significantly less tumor distortion than the unconstrained algorithm: considering the tumor volume determined from standard uptake value maps, the post-registration median tumor volume changes, and the 25th and 75th quantiles were 3.42% (0%, 13.39%) and 16.93% (9.21%, 49.93%) for the constrained and unconstrained algorithms, respectively (p = 0.002), while the bending energy (a measure of the smoothness of the deformation) was 0.0015 (0.0005, 0.012) and 0.017 (0.005, 0.044), respectively (p = 0.005). The results indicate that the constrained ABA algorithm can accurately align prone breast FDG-PET images acquired at different time points while keeping the tumor from being substantially compressed or distorted. NCT00474604.

Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein.

PubMed

Fan, Zhen; Calsolaro, Valeria; Atkinson, Rebecca A; Femminella, Grazia D; Waldman, Adam; Buckley, Christopher; Trigg, William; Brooks, David J; Hinz, Rainer; Edison, Paul

2016-11-01

Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ( 18 F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18 F-GE180 PET in (older) healthy controls. Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18 F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. 18 F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (V T ) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18 F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a V T highly consistent with V T in the kinetic model, which could be used for voxelwise analysis. We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18 F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low V T , the methodology presented here forms the basis for quantification for future PET studies using 18 F-GE180 in different pathologies. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

PubMed

Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

2013-10-01

Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

PubMed

Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

2016-01-01

Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

COMPANION ANIMALS SYMPOSIUM: Future aspects and perceptions of companion animal nutrition and sustainability.

PubMed

Deng, P; Swanson, K S

2015-03-01

Companion animals play an important role in our lives and are now considered to be and treated as family members in a majority of households in the United States. Because of the high number of pets that now exist, an increasingly stronger pet-human bond, and the importance placed on health and longevity, the pet food industry has realized steady growth over the last few decades. Despite past successes and opportunities that exist in the future, there are also challenges that must be considered. This review will present a brief overview of the current pet food industry and address some of the key issues moving forward. In regards to companion animal research, recent advances and future needs in the areas of canine and feline metabolism, aging, clinical disease, and the gut microbiome using molecular and high-throughput assays; chemical, in vitro, and in vivo testing of feed ingredients; and innovative pet food processing methods is discussed. Training the future workforce for the pet food industry is also of great importance. Recent trends on student demographics and their species and careers of interest, changing animal science department curricula, and technology's impact on instruction are provided. Finally, the sustainability of the pet food industry is discussed. Focus was primarily placed on the disconnect that exists between opinions and trends of consumers and the nutrient recommendations for dogs and cats, the desire for increasing use of animal-based and human-grade products, the overfeeding of pets and the pet obesity crisis, and the issues that involve the evaluation of primary vs. secondary products in terms of sustainability. Moving forward, the pet food industry will need to anticipate and address challenges that arise, especially those pertaining to consumer expectations, the regulatory environment, and sustainability. Given the already strong and increasingly dynamic market for pet foods and supplies, an academic environment primed to supply a skilled workforce, and continued industry support for basic and applied research initiatives, the future of the pet food industry looks very bright.

Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

PubMed

Mehta, Nehal N; Torigian, Drew A; Gelfand, Joel M; Saboury, Babak; Alavi, Abass

2012-05-02

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is calculated by dividing the arterial SUV by the venous blood pool SUV. This method has shown to represent a stable, reproducible phenotype over time, has a high sensitivity for detection of vascular inflammation, and also has high inter-and intra-reader reliability. Here we present our methodology for patient preparation, image acquisition, and quantification of atherosclerotic plaque activity and vascular inflammation using SUV, TBR, and a global parameter called the metabolic volumetric product (MVP). These approaches may be applied to assess vascular inflammation in various study samples of interest in a consistent fashion as we have shown in several prior publications.

Usefulness of whole-body fluorine-18-fluorodeoxyglucose positron emission tomography in patients with large-vessel vasculitis: a systematic review.

PubMed

Treglia, Giorgio; Mattoli, Maria Vittoria; Leccisotti, Lucia; Ferraccioli, Gianfranco; Giordano, Alessandro

2011-10-01

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with fluorine-18-fluorodeoxyglucose (FDG) in patients with large-vessel vasculitis (LVV). A comprehensive literature search of published studies through April 2011 in PubMed/MEDLINE and Scopus databases regarding whole-body FDG-PET and PET/CT in patients with LVV was performed. We identified 32 studies including 604 LVV patients. The main findings of these studies are presented. The conclusions are the following: (1) FDG-PET and PET/CT are useful imaging methods in the initial diagnosis and in the assessment of activity and extent of disease in patients with LVV; (2) the correlation between FDG-PET findings and serological levels of inflammatory markers, as well as the usefulness of FDG-PET and PET/CT in evaluating treatment response, remains unclear; (3) it appears that there is a superiority of FDG-PET and PET/CT over conventional imaging methods in the diagnosis of LVV, but not in assessing disease activity under immunosuppressive treatment, in predicting relapse or in evaluating vascular complications; and (4) given the heterogeneity between studies with regard to PET analysis and diagnostic criteria, a standardization of the technique is needed.

Diagnostic performance of FDG PET or PET/CT in prosthetic infection after arthroplasty: a meta-analysis.

PubMed

Jin, H; Yuan, L; Li, C; Kan, Y; Hao, R; Yang, J

2014-03-01

The purpose of this study was to systematically review and perform a meta-analysis of published data regarding the diagnostic performance of positron emission tomography (PET) or PET/computed tomography (PET/CT) in prosthetic infection after arthroplasty. A comprehensive computer literature search of studies published through May 31, 2012 regarding PET or PET/CT in patients suspicious of prosthetic infection was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of PET or PET/CT in patients suspicious of prosthetic infection on a per prosthesis-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of PET or PET/CT in patients with suspicious of prosthetic infection. Fourteen studies comprising 838 prosthesis with suspicious of prosthetic infection after arthroplasty were included in this meta-analysis. The pooled sensitivity of PET or PET/CT in detecting prosthetic infection was 86% (95% confidence interval [CI] 82-90%) on a per prosthesis-based analysis. The pooled specificity of PET or PET/CT in detecting prosthetic infection was 86% (95% CI 83-89%) on a per prosthesis-based analysis. The area under the ROC curve was 0.93 on a per prosthesis-based analysis. In patients suspicious of prosthetic infection, FDG PET or PET/CT demonstrated high sensitivity and specificity. FDG PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false positive results and influcing factors should kept in mind.

New cardiac cameras: single-photon emission CT and PET.

PubMed

Slomka, Piotr J; Berman, Daniel S; Germano, Guido

2014-07-01

Nuclear cardiology instrumentation has evolved significantly in the recent years. Concerns about radiation dose and long acquisition times have propelled developments of dedicated high-efficiency cardiac SPECT scanners. Novel collimator designs, such as multipinhole or locally focusing collimators arranged in geometries that are optimized for cardiac imaging, have been implemented to enhance photon-detection sensitivity. Some of these new SPECT scanners use solid-state photon detectors instead of photomultipliers to improve image quality and to reduce the scanner footprint. These new SPECT devices allow dramatic up to 7-fold reduction in acquisition times or similar reduction in radiation dose. In addition, new hardware for photon attenuation correction allowing ultralow radiation doses has been offered by some vendors. To mitigate photon attenuation artifacts for the new SPECT scanners not equipped with attenuation correction hardware, 2-position (upright-supine or prone-supine) imaging has been proposed. PET hardware developments have been primarily driven by the requirements of oncologic imaging, but cardiac imaging can benefit from improved PET image quality and improved sensitivity of 3D systems. The time-of-flight reconstruction combined with resolution recovery techniques is now implemented by all major PET vendors. These new methods improve image contrast and image resolution and reduce image noise. High-sensitivity 3D PET without interplane septa allows reduced radiation dose for cardiac perfusion imaging. Simultaneous PET/MR hybrid system has been developed. Solid-state PET detectors with avalanche photodiodes or digital silicon photomultipliers have been introduced, and they offer improved imaging characteristics and reduced sensitivity to electromagnetic MR fields. Higher maximum count rate of the new PET detectors allows routine first-pass Rb-82 imaging, with 3D PET acquisition enabling clinical utilization of dynamic imaging with myocardial flow measurements for this tracer. The availability of high-end CT component in most PET/CT configurations enables hybrid multimodality cardiac imaging protocols with calcium scoring or CT angiography or both. Copyright © 2014. Published by Elsevier Inc.

Combining MRI With PET for Partial Volume Correction Improves Image-Derived Input Functions in Mice

NASA Astrophysics Data System (ADS)

Evans, Eleanor; Buonincontri, Guido; Izquierdo, David; Methner, Carmen; Hawkes, Rob C.; Ansorge, Richard E.; Krieg, Thomas; Carpenter, T. Adrian; Sawiak, Stephen J.

2015-06-01

Accurate kinetic modelling using dynamic PET requires knowledge of the tracer concentration in plasma, known as the arterial input function (AIF). AIFs are usually determined by invasive blood sampling, but this is prohibitive in murine studies due to low total blood volumes. As a result of the low spatial resolution of PET, image-derived input functions (IDIFs) must be extracted from left ventricular blood pool (LVBP) ROIs of the mouse heart. This is challenging because of partial volume and spillover effects between the LVBP and myocardium, contaminating IDIFs with tissue signal. We have applied the geometric transfer matrix (GTM) method of partial volume correction (PVC) to 12 mice injected with 18F - FDG affected by a Myocardial Infarction (MI), of which 6 were treated with a drug which reduced infarction size [1]. We utilised high resolution MRI to assist in segmenting mouse hearts into 5 classes: LVBP, infarcted myocardium, healthy myocardium, lungs/body and background. The signal contribution from these 5 classes was convolved with the point spread function (PSF) of the Cambridge split magnet PET scanner and a non-linear fit was performed on the 5 measured signal components. The corrected IDIF was taken as the fitted LVBP component. It was found that the GTM PVC method could recover an IDIF with less contamination from spillover than an IDIF extracted from PET data alone. More realistic values of Ki were achieved using GTM IDIFs, which were shown to be significantly different (p <; 0.05) between the treated and untreated groups.

Bubble column and CFD simulation for chemical recycling of polyethylene terephthalate

NASA Astrophysics Data System (ADS)

Alzuhairi, Mohammed

2018-05-01

Computational Fluid Dynamics (CFD) is an important simulation tool, which uses powerful computer to get optimal design in industrial processes. New approach technique of bubble column for three phases has been used with respect to chemical recycling of Polyethylene Terephthalate (PET). The porous ceramic has been used in thin plate (5 mm) with a narrow pore size distribution. Excellent agreement between CFD has been predicted and experimental profiles of hold-up and velocity close to wall have been observed for a column diameter 0.08 m, column height 0.15 m (HD), and superficial gas velocity (VG) 0.05 m/s. The main purpose of the current study is to highlight depolymerization of PET chemically by using the close system of Ethylene Glycol, PET-Catalyzed, and Nitrogen glycolysis process in bubble column of three phases technique by using Nano catalyst, SiO2 with various weight percent (0.01, 0.02, 0.05, 0.1, 0.2, and 0.5) based on PET weight and preheated Nitrogen up to 100° C by extra heater in bubble column reactor. The depolymerization time could be reduced in order to improve heat and mass transfer in comparison with the traditional methods. Little amount not exceeding 0.01% of Nano SiO2 is enough for completing depolymerization. The final product of PET depolymerization has full characterization by FTIR, AFM, CHN tests and has been used as a vital additive for Bitumen, it has been investigated as a moisture-proof, water seepage-proof material, and as a tough resistant to environmental conditions.

Colorectal cancer staging: comparison of whole-body PET/CT and PET/MR.

PubMed

Catalano, Onofrio A; Coutinho, Artur M; Sahani, Dushyant V; Vangel, Mark G; Gee, Michael S; Hahn, Peter F; Witzel, Thomas; Soricelli, Andrea; Salvatore, Marco; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce R; Gervais, Debra

2017-04-01

Correct staging is imperative for colorectal cancer (CRC) since it influences both prognosis and management. Several imaging methods are used for this purpose, with variable performance. Positron emission tomography-magnetic resonance (PET/MR) is an innovative imaging technique recently employed for clinical application. The present study was undertaken to compare the staging accuracy of whole-body positron emission tomography-computed tomography (PET/CT) with whole-body PET/MR in patients with both newly diagnosed and treated colorectal cancer. Twenty-six patients, who underwent same day whole-body (WB) PET/CT and WB-PET/MR, were evaluated. PET/CT and PET/MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Correct staging was compared between methods using McNemar's Chi square test. The two methods were in agreement and correct for 18/26 (69%) patients, and in agreement and incorrect for one patient (3.8%). PET/MR and PET/CT stages for the remaining 7/26 patients (27%) were discordant, with PET/MR staging being correct in all seven cases. PET/MR significantly outperformed PET/CT overall for accurate staging (P = 0.02). PET/MR outperformed PET/CT in CRC staging. PET/MR might allow accurate local and distant staging of CRC patients during both at the time of diagnosis and during follow-up.

SAMPEX/PET model of the low altitude trapped proton environment

NASA Astrophysics Data System (ADS)

Heynderickx, D.; Looper, M. D.; Blake, J. B.

The low-altitude trapped proton population exhibits strong time variations related to geomagnetic secular variation and neutral atmosphere conditions. The flux measurements of the Proton Electron Telescope (PET) onboard the polar satellite SAMPEX constitute an adequate data set to distinguish different time scales and to characterise the respective variations. As a first step towards building a dynamic model of the low altitude proton environment we binned the 1995-1996 PET data into a model map with functional dependencies of the proton fluxes on the F10.7 solar radio flux and on the time of year to represent variations on the time scale of the solar cycle and seasonal variations. Now, a full solar cycle of SAMPEX/PET data is available, so that the preliminary model could be extended. The secular variation of the geomagnetic field is included in the model, as it is constructed using Kaufmann's K=I √{B} instead of McIlwain's L as a map coordinate.

Healable Antifouling Films Composed of Partially Hydrolyzed Poly(2-ethyl-2-oxazoline) and Poly(acrylic acid).

PubMed

Li, Yixuan; Pan, Tiezheng; Ma, Benhua; Liu, Junqiu; Sun, Junqi

2017-04-26

Antifouling polymeric films can prevent undesirable adhesion of bacteria but are prone to accidental scratches, leading to a loss of their antifouling functions. To solve this problem, we report the fabrication of healable antifouling polymeric films by layer-by-layer assembly of partially hydrolyzed poly(2-ethyl-2-oxazoline) (PEtOx-EI-7%) and poly(acrylic acid) (PAA) based on hydrogen-bonding interaction as the driving force. The thermally cross-linked (PAA/PEtOx-EI-7%)*100 films show strong resistance to adhesion of both Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria due to the high surface and bulk concentration of the antifouling polymer PEtOx-EI-7%. Meanwhile, the dynamic nature of the hydrogen-bonding interactions and the high mobility of the polymers in the presence of water enable repeated healing of cuts of several tens of micrometers wide in cross-linked (PAA/PEtOx-EI-7%)*100 films to fully restore their antifouling function.

Can human allergy drug fexofenadine, an antagonist of histamine (H1) receptor, be used to treat dog and cat? Homology modeling, docking and molecular dynamic Simulation of three H1 receptors in complex with fexofenadine.

PubMed

Sader, Safaa; Cai, Jun; Muller, Anna C G; Wu, Chun

2017-08-01

Fexofenadine, a potent antagonist to human histamine 1 (H 1 ) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H 1 receptor, the similar studies on non-human pet H 1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H 1 receptors were built based on the crystal structure of human H 1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H 1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H 1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H 1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship Between Ktrans and K1 with Simultaneous Versus Separate MR/PET in Rabbits with VX2 Tumors.

PubMed

Lee, Kyung Hee; Kang, Seung Kwan; Goo, Jin Mo; Lee, Jae Sung; Cheon, Gi Jeong; Seo, Seongho; Hwang, Eui Jin

2017-03-01

To compare the relationship between K trans from DCE-MRI and K 1 from dynamic 13 N-NH 3 -PET, with simultaneous and separate MR/PET in the VX-2 rabbit carcinoma model. MR/PET was performed simultaneously and separately, 14 and 15 days after VX-2 tumor implantation at the paravertebral muscle. The K trans and K 1 values were estimated using an in-house software program. The relationships between K trans and K 1 were analyzed using Pearson's correlation coefficients and linear/non-linear regression function. Assuming a linear relationship, K trans and K 1 exhibited a moderate positive correlations with both simultaneous (r=0.54-0.57) and separate (r=0.53-0.69) imaging. However, while the K trans and K 1 from separate imaging were linearly correlated, those from simultaneous imaging exhibited a non-linear relationship. The amount of change in K 1 associated with a unit increase in K trans varied depending on K trans values. The relationship between K trans and K 1 may be mis-interpreted with separate MR and PET acquisition. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) Pharmacokinetics in FaDu Xenograft Tumors and Correlation With Microscopic Markers of Hypoxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCall, Keisha C.; Humm, John L.; Bartlett, Rachel

Purpose: The behavior of copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) ({sup 64}Cu-ATSM) in hypoxic tumors was examined through a combination of in vivo dynamic positron emission tomography (PET) and ex vivo autoradiographic and histologic evaluation using a xenograft model of head-and-neck squamous cell carcinoma. Methods and Materials: {sup 64}Cu-ATSM was administered during dynamic PET imaging, and temporal changes in {sup 64}Cu-ATSM distribution within tumors were evaluated for at least 1 hour and up to 18 hours. Animals were sacrificed at either 1 hour (cohort A) or after 18 hours (cohort B) postinjection of radiotracer and autoradiography performed. Ex vivo analysis of microenvironment subregions was conductedmore » by immunohistochemical staining for markers of hypoxia (pimonidazole hydrochloride) and blood flow (Hoechst-33342). Results: Kinetic analysis revealed rapid uptake of radiotracer by tumors. The net influx (K{sub i}) constant was 12-fold that of muscle, whereas the distribution volume (V{sub d}) was 5-fold. PET images showed large tumor-to-muscle ratios, which continually increased over the entire 18-hour course of imaging. However, no spatial changes in {sup 64}Cu-ATSM distribution occurred in PET imaging at 20 minutes postinjection. Microscopic intratumoral distribution of {sup 64}Cu-ATSM and pimonidazole were not correlated at 1 hour or after 18 hours postinjection, nor was {sup 64}Cu-ATSM and Hoechst-33342. Conclusions: The oxygen partial pressures at which {sup 64}Cu-ATSM and pimonidazole are reduced and bound in cells are theorized to be distinct and separable. However, this study demonstrated that microscopic distributions of these tracers within tumors are independent. Researchers have shown {sup 64}Cu-ATSM uptake to be specific to malignant expression, and this work has also demonstrated clear tumor targeting by the radiotracer.« less

Malignant pleural disease: diagnosis by using diffusion-weighted and dynamic contrast-enhanced MR imaging--initial experience.

PubMed

Coolen, Johan; De Keyzer, Frederik; Nafteux, Philippe; De Wever, Walter; Dooms, Christophe; Vansteenkiste, Johan; Roebben, Ilse; Verbeken, Eric; De Leyn, Paul; Van Raemdonck, Dirk; Nackaerts, Kristiaan; Dymarkowski, Steven; Verschakelen, Johny

2012-06-01

To investigate the use of diffusion-weighted (DW) imaging for differentiating benign lesions from malignant pleural disease (MPD) and to retrospectively assess dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging acquisitions to find out whether combining these measurements with DW imaging could improve the diagnostic value of DW imaging. This study was approved by the local ethics committee, and all patients provided written informed consent. Thirty-one consecutive patients with pleural abnormalities suspicious for MPD underwent whole-body positron emission tomography (PET)/computed tomography (CT) and thorax MR examinations. Diagnostic thoracoscopy with histopathologic analysis of pleural biopsies served as the reference standard. First-line evaluation of each suspicious lesion was performed by using the apparent diffusion coefficient (ADC) calculated from the DW image, and the optimal cutoff value was found by using receiver operating characteristic curve analysis. Afterward, DCE MR imaging data were used to improve the diagnosis in the range of ADCs where DW imaging results were equivocal. Sensitivity, specificity, and accuracy of PET/CT for diagnosis of MPD were 100%, 35.3%, and 64.5%. The optimal ADC threshold to differentiate benign lesions from MPD with DW MR imaging was 1.52 × 10(-3) mm(2)/sec, with sensitivity, specificity, and accuracy of 71.4%, 100%, and 87.1%, respectively. This result could be improved to 92.8%, 94.1%, and 93.5%, respectively, when DCE MR imaging data were included in those cases where ADC was between 1.52 and 2.00 × 10(-3) mm(2)/sec. A total of 20 patients had disease diagnosed correctly, nine had disease diagnosed incorrectly, and two cases were undetermined with PET/CT. DW imaging helped stage disease correctly in 27 patients and incorrectly in four. The undetermined cases at PET/CT were correctly diagnosed at MR imaging. DW imaging is a promising tool for differentiating MPD from benign lesions, with high accuracy, and supplementation with DCE MR imaging seems to further improve sensitivity.

Image-derived input function with factor analysis and a-priori information.

PubMed

Simončič, Urban; Zanotti-Fregonara, Paolo

2015-02-01

Quantitative PET studies often require the cumbersome and invasive procedure of arterial cannulation to measure the input function. This study sought to minimize the number of necessary blood samples by developing a factor-analysis-based image-derived input function (IDIF) methodology for dynamic PET brain studies. IDIF estimation was performed as follows: (a) carotid and background regions were segmented manually on an early PET time frame; (b) blood-weighted and tissue-weighted time-activity curves (TACs) were extracted with factor analysis; (c) factor analysis results were denoised and scaled using the voxels with the highest blood signal; (d) using population data and one blood sample at 40 min, whole-blood TAC was estimated from postprocessed factor analysis results; and (e) the parent concentration was finally estimated by correcting the whole-blood curve with measured radiometabolite concentrations. The methodology was tested using data from 10 healthy individuals imaged with [(11)C](R)-rolipram. The accuracy of IDIFs was assessed against full arterial sampling by comparing the area under the curve of the input functions and by calculating the total distribution volume (VT). The shape of the image-derived whole-blood TAC matched the reference arterial curves well, and the whole-blood area under the curves were accurately estimated (mean error 1.0±4.3%). The relative Logan-V(T) error was -4.1±6.4%. Compartmental modeling and spectral analysis gave less accurate V(T) results compared with Logan. A factor-analysis-based IDIF for [(11)C](R)-rolipram brain PET studies that relies on a single blood sample and population data can be used for accurate quantification of Logan-V(T) values.

Washout of ⁸²Rb as a marker of impaired tissue integrity, obtained by list-mode cardiac PET/CT: relationship with perfusion/metabolism patterns of myocardial viability.

PubMed

Chien, David T; Bravo, Paco; Higuchi, Takahiro; Merrill, Jennifer; Bengel, Frank M

2011-08-01

Myocardial washout of the potassium analogue (82)Rb may indicate tissue impairment. Few studies have evaluated its usefulness for viability assessment, and controversial results were reported. We revisited this topic using list-mode positron emission tomography (PET)/CT. A total of 22 patients with chronic ischemic cardiomyopathy (ICM) and 11 control subjects with normal CT coronary angiogram were studied. Rest (82)Rb PET/CT studies were acquired in list mode and resampled to static, gated, and dynamic images. Using a 17-segment model, (82)Rb washout was determined by monoexponential fitting of myocardial time-activity curves. In ICM patients, (18)F-fluorodeoxyglucose (FDG) studies were obtained in the same session and segments were classified as normally perfused, mismatch, or matched defect. (82)Rb washout was minimal and homogeneous in control subjects. Normally perfused segments of ICM did not differ (p = 0.33). ICM patients had a left ventricular ejection fraction (LVEF) of 25 ± 12%, 25/353 mismatched, and 46/353 matched defect segments. (82)Rb washout was higher in hypoperfused vs normal segments (p < 0.05), but not different between mismatch and matched defect (p = 0.18). Intraindividual analysis in nine patients showing both FDG mismatch and matched defect confirmed absence of differences. Overall, segmental (82)Rb washout correlated inversely with (82)Rb uptake (r = -0.70; p < 0.05) and less well with FDG uptake (r = -0.31; p < 0.05). Using state-of-the-art PET/CT technology for myocardial viability assessment, (82)Rb washout does not distinguish between perfusion/metabolism patterns of hibernating myocardium and scar. Tissue integrity may be at least partially impaired in hibernation.

Human Brown Adipose Tissue Temperature and Fat Fraction Are Related to Its Metabolic Activity.

PubMed

Koskensalo, Kalle; Raiko, Juho; Saari, Teemu; Saunavaara, Virva; Eskola, Olli; Nuutila, Pirjo; Saunavaara, Jani; Parkkola, Riitta; Virtanen, Kirsi A

2017-04-01

The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron emission tomography (PET). The aim of this study was to use proton magnetic resonance spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of BAT and white adipose tissue (WAT) are associated with BAT metabolic activity determined by deoxy-2-18F-fluoro-d-glucose (18F-FDG)-PET. Ten healthy subjects (four women, six men; 25 to 45 years of age) were studied using PET-magnetic resonance imaging during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on eight subjects. The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid-burning capacity of BAT associated with whole-body insulin sensitivity. During cold exposure, the FF of BAT was lower than at room temperature, and cold-induced FF of BAT associated inversely with high-density lipoprotein and directly with low-density lipoprotein cholesterol. Both 1H MRS-derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid-burning capacity of BAT and whole-body insulin sensitivity emphasizes the role of BAT in glucose handling. Furthermore, the relation of FF to high-density lipoprotein and low-density lipoprotein cholesterol suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load. Copyright © 2017 Endocrine Society

Pet Ownership among Homeless Youth: Associations with Mental Health, Service Utilization and Housing Status

PubMed Central

Rhoades, Harmony; Winetrobe, Hailey; Rice, Eric

2014-01-01

As many as 25% of homeless persons have pets. To our knowledge, pet ownership has not been studied quantitatively with homeless youth. This study examined pet ownership among 398 homeless youth utilizing two Los Angeles drop-in centers. Twenty-three percent of homeless youth had a pet. The majority of pet owners reported that their pets kept them company and made them feel loved; nearly half reported that their pets made it more difficult to stay in a shelter. Pet owners reported fewer symptoms of depression and loneliness than their non-pet owning peers. Pet ownership was associated with decreased utilization of housing and job-finding services, and decreased likelihood of currently staying in a shelter. These findings elucidate many of the positive benefits of pet ownership for homeless youth, but importantly highlight that pet ownership may negatively impact housing options. Housing and other services must be sensitive to the needs of homeless youth with pets. PMID:24728815

Pet ownership among homeless youth: associations with mental health, service utilization and housing status.

PubMed

Rhoades, Harmony; Winetrobe, Hailey; Rice, Eric

2015-04-01

As many as 25 % of homeless persons have pets. To our knowledge, pet ownership has not been studied quantitatively with homeless youth. This study examined pet ownership among 398 homeless youth utilizing two Los Angeles drop-in centers. Twenty-three percent of homeless youth had a pet. The majority of pet owners reported that their pets kept them company and made them feel loved; nearly half reported that their pets made it more difficult to stay in a shelter. Pet owners reported fewer symptoms of depression and loneliness than their non-pet owning peers. Pet ownership was associated with decreased utilization of housing and job-finding services, and decreased likelihood of currently staying in a shelter. These findings elucidate many of the positive benefits of pet ownership for homeless youth, but importantly highlight that pet ownership may negatively impact housing options. Housing and other services must be sensitive to the needs of homeless youth with pets.

Childhood Attachment to Pets: Associations between Pet Attachment, Attitudes to Animals, Compassion, and Humane Behaviour

PubMed Central

Hawkins, Roxanne D.; Williams, Joanne M.

2017-01-01

Attachment to pets has an important role in children’s social, emotional, and cognitive development, mental health, well-being, and quality of life. This study examined associations between childhood attachment to pets and caring and friendship behaviour, compassion, and attitudes towards animals. This study also examined socio-demographic differences, particularly pet ownership and pet type. A self-report survey of over one thousand 7 to 12 year-olds in Scotland, UK, revealed that the majority of children are strongly attached to their pets, but attachment scores differ depending on pet type and child gender. Analysis revealed that attachment to pets is facilitated by compassion and caring and pet-directed friendship behaviours and that attachment to pets significantly predicts positive attitudes towards animals. The findings have implications for the promotion of prosocial and humane behaviour. Encouraging children to participate in pet care behaviour may promote attachment between children and their pet, which in turn may have a range of positive outcomes for both children (such as reduced aggression, better well-being, and quality of life) and pets (such as humane treatment). This study enhances our understanding of childhood pet attachment and has implications for humane education and promoting secure emotional attachments in childhood. PMID:28481256

Childhood Attachment to Pets: Associations between Pet Attachment, Attitudes to Animals, Compassion, and Humane Behaviour.

PubMed

Hawkins, Roxanne D; Williams, Joanne M; Scottish Society For The Prevention Of Cruelty To Animals Scottish Spca

2017-05-06

Attachment to pets has an important role in children's social, emotional, and cognitive development, mental health, well-being, and quality of life. This study examined associations between childhood attachment to pets and caring and friendship behaviour, compassion, and attitudes towards animals. This study also examined socio-demographic differences, particularly pet ownership and pet type. A self-report survey of over one thousand 7 to 12 year-olds in Scotland, UK, revealed that the majority of children are strongly attached to their pets, but attachment scores differ depending on pet type and child gender. Analysis revealed that attachment to pets is facilitated by compassion and caring and pet-directed friendship behaviours and that attachment to pets significantly predicts positive attitudes towards animals. The findings have implications for the promotion of prosocial and humane behaviour. Encouraging children to participate in pet care behaviour may promote attachment between children and their pet, which in turn may have a range of positive outcomes for both children (such as reduced aggression, better well-being, and quality of life) and pets (such as humane treatment). This study enhances our understanding of childhood pet attachment and has implications for humane education and promoting secure emotional attachments in childhood.

Double Jeopardy: Insurance, Animal Harm, and Domestic Violence.

PubMed

Signal, Tania; Taylor, Nik; Burke, Karena J; Brownlow, Luke

2018-05-01

Although the role of companion animals within the dynamic of domestic violence (DV) is increasingly recognized, the overlap of animal harm and insurance discrimination for victims/survivors of DV has not been considered. Prompted by a case study presented in a National Link Coalition LINK-Letter, this research note examines "Pet Insurance" policies available in Australia and whether nonaccidental injury caused by an intimate partner would be covered. We discuss the implications of exclusion criteria for victims/survivors of DV, shelters providing places for animals within a DV dynamic, and, more broadly, for cross- or mandatory-reporting (of animal harm) initiatives.

Family pet ownership during childhood: findings from a UK birth cohort and implications for public health research.

PubMed

Westgarth, Carri; Heron, Jon; Ness, Andy R; Bundred, Peter; Gaskell, Rosalind M; Coyne, Karen P; German, Alexander J; McCune, Sandra; Dawson, Susan

2010-10-01

In developed nations, approximately half of household environments contain pets. Studies of Human-Animal Interaction (HAI) have proposed that there are health benefits and risks associated with pet ownership. However, accurately demonstrating and understanding these relationships first requires a better knowledge of factors associated with ownership of different pet types. A UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were used to collect pet ownership data from the mothers, from gestation to child age 10 years old. 14,663 children were included in the study, of which mothers of 13,557 reported pet information at gestation, and 7,800 by age 10. Pet types recorded include cat, dog, rabbit, rodent, bird, fish and tortoise/turtle. The dataset also contains a number of demographic, socioeconomic and behavioural variables relevant to human health behaviour. Logistic regression was used to build multivariable models for ownership of each pet type at age 7 years. Family pet ownership increased during childhood, in particular rabbits, rodents and fish. A number of socioeconomic and demographic factors were associated with ownership of different pet types and the effects differed depending on the pet type studied. Variables which require consideration by researchers include gender, presence of older siblings, ethnicity, maternal and paternal education, maternal and paternal social class, maternal age, number of people in the household, house type, and concurrent ownership of other pets. Whether the mother had pets during her childhood was a strong predictor of pet ownership in all models. In HAI studies, care should be taken to control for confounding factors, and to treat each pet type individually. ALSPAC and other similar birth cohorts can be considered a potential resource for research into the effects of pet ownership during childhood.

Family Pet Ownership during Childhood: Findings from a UK Birth Cohort and Implications for Public Health Research

PubMed Central

Westgarth, Carri; Heron, Jon; Ness, Andy R.; Bundred, Peter; Gaskell, Rosalind M.; Coyne, Karen P.; German, Alexander J.; McCune, Sandra; Dawson, Susan

2010-01-01

In developed nations, approximately half of household environments contain pets. Studies of Human-Animal Interaction (HAI) have proposed that there are health benefits and risks associated with pet ownership. However, accurately demonstrating and understanding these relationships first requires a better knowledge of factors associated with ownership of different pet types. A UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were used to collect pet ownership data from the mothers, from gestation to child age 10 years old. 14,663 children were included in the study, of which mothers of 13,557 reported pet information at gestation, and 7,800 by age 10. Pet types recorded include cat, dog, rabbit, rodent, bird, fish and tortoise/turtle. The dataset also contains a number of demographic, socioeconomic and behavioural variables relevant to human health behaviour. Logistic regression was used to build multivariable models for ownership of each pet type at age 7 years. Family pet ownership increased during childhood, in particular rabbits, rodents and fish. A number of socioeconomic and demographic factors were associated with ownership of different pet types and the effects differed depending on the pet type studied. Variables which require consideration by researchers include gender, presence of older siblings, ethnicity, maternal and paternal education, maternal and paternal social class, maternal age, number of people in the household, house type, and concurrent ownership of other pets. Whether the mother had pets during her childhood was a strong predictor of pet ownership in all models. In HAI studies, care should be taken to control for confounding factors, and to treat each pet type individually. ALSPAC and other similar birth cohorts can be considered a potential resource for research into the effects of pet ownership during childhood. PMID:21139856

Novel imaging strategies for the detection of prosthetic heart valve obstruction and endocarditis.

PubMed

Tanis, W; Budde, R P J; van der Bilt, I A C; Delemarre, B; Hoohenkerk, G; van Rooden, J-K; Scholtens, A M; Habets, J; Chamuleau, S

2016-02-01

Prosthetic heart valve (PHV) dysfunction remains difficult to recognise correctly by two-dimensional (2D) transthoracic and transoesophageal echocardiography (TTE/TEE). ECG-triggered multidetector-row computed tomography (MDCT), 18-fluorine-fluorodesoxyglucose positron emission tomography including low-dose CT (FDG-PET) and three-dimensional transoesophageal echocardiography (3D-TEE) may have additional value. This paper reviews the role of these novel imaging tools in the field of PHV obstruction and endocarditis.For acquired PHV obstruction, MDCT is of additional value in mechanical PHVs to differentiate pannus from thrombus as well as to dynamically study leaflet motion and opening/closing angles. For biological PHV obstruction, additional imaging is not beneficial as it does not change patient management. When performed on top of 2D-TTE/TEE, MDCT has additional value for the detection of both vegetations and pseudoaneurysms/abscesses in PHV endocarditis. FDG-PET has no complementary value for the detection of vegetations; however, it appears more sensitive in the early detection of pseudoaneurysms/abscesses. Furthermore, FDG-PET enables the detection of metastatic and primary extra-cardiac infections. Evidence for the additional value of 3D-TEE is scarce.As clinical implications are major, clinicians should have a low threshold to perform additional MDCT in acquired mechanical PHV obstruction. For suspected PHV endocarditis, both FDG-PET and MDCT have complementary value.

Real-Time Imaging System for the OpenPET

NASA Astrophysics Data System (ADS)

Tashima, Hideaki; Yoshida, Eiji; Kinouchi, Shoko; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo; Suga, Mikio; Haneishi, Hideaki; Yamaya, Taiga

2012-02-01

The OpenPET and its real-time imaging capability have great potential for real-time tumor tracking in medical procedures such as biopsy and radiation therapy. For the real-time imaging system, we intend to use the one-pass list-mode dynamic row-action maximum likelihood algorithm (DRAMA) and implement it using general-purpose computing on graphics processing units (GPGPU) techniques. However, it is difficult to make consistent reconstructions in real-time because the amount of list-mode data acquired in PET scans may be large depending on the level of radioactivity, and the reconstruction speed depends on the amount of the list-mode data. In this study, we developed a system to control the data used in the reconstruction step while retaining quantitative performance. In the proposed system, the data transfer control system limits the event counts to be used in the reconstruction step according to the reconstruction speed, and the reconstructed images are properly intensified by using the ratio of the used counts to the total counts. We implemented the system on a small OpenPET prototype system and evaluated the performance in terms of the real-time tracking ability by displaying reconstructed images in which the intensity was compensated. The intensity of the displayed images correlated properly with the original count rate and a frame rate of 2 frames per second was achieved with average delay time of 2.1 s.

Treatment for Animal Bites

MedlinePlus

... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... by animals the child knows, including the family pet. Although the injury often is minor, biting does ...

Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT: 5D-PET.

PubMed

Nordström, Jonny; Kero, Tanja; Harms, Hendrik Johannes; Widström, Charles; Flachskampf, Frank A; Sörensen, Jens; Lubberink, Mark

2017-11-14

Quantitative measurement of myocardial blood flow (MBF) is of increasing interest in the clinical assessment of patients with suspected coronary artery disease (CAD). 15 O-water positron emission tomography (PET) is considered the gold standard for non-invasive MBF measurements. However, calculation of left ventricular (LV) volumes and ejection fraction (EF) is not possible from standard 15 O-water uptake images. The purpose of the present work was to investigate the possibility of calculating LV volumes and LVEF from cardiac-gated parametric blood volume (V B ) 15 O-water images and from first pass (FP) images. Sixteen patients with mitral or aortic regurgitation underwent an eight-gate dynamic cardiac-gated 15 O-water PET/CT scan and cardiac MRI. V B and FP images were generated for each gate. Calculations of end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV) and LVEF were performed with automatic segmentation of V B and FP images, using commercially available software. LV volumes and LVEF were calculated with surface-, count-, and volume-based methods, and the results were compared with gold standard MRI. Using V B images, high correlations between PET and MRI ESV (r = 0.89, p < 0.001), EDV (r = 0.85, p < 0.001), SV (r = 0.74, p = 0.006) and LVEF (r = 0.72, p = 0.008) were found for the volume-based method. Correlations for FP images were slightly, but not significantly, lower than those for V B images when compared to MRI. Surface- and count-based methods showed no significant difference compared with the volume-based correlations with MRI. The volume-based method showed the best agreement with MRI with no significant difference on average for EDV and LVEF but with an overestimation of values for ESV (14%, p = 0.005) and SV (18%, p = 0.004) when using V B images. Using FP images, none of the parameters showed a significant difference from MRI. Inter-operator repeatability was excellent for all parameters (ICC > 0.86, p < 0.001). Calculation of LV volumes and LVEF from dynamic 15 O-water PET is feasible and shows good correlation with MRI. However, the analysis method is laborious, and future work is needed for more automation to make the method more easily applicable in a clinical setting.

New fluorescent perylene bisimide indicators--a platform for broadband pH optodes.

PubMed

Aigner, Daniel; Borisov, Sergey M; Klimant, Ingo

2011-06-01

Asymmetric perylene bisimide (PBI) dyes are prepared and are shown to be suitable for the preparation of fluorescence chemosensors for pH. They carry one amino-functional substituent which introduces pH sensitivity via photoinduced electron transfer (PET) while the other one increases solubility. The luminescence quantum yields for the new indicators exceed 75% in the protonated form. The new indicators are non-covalently entrapped in polyurethane hydrogel D4 and poly(hydroxyalkylmethacrylates). Several PET functions including aliphatic and aromatic amino groups were successfully used to tune the dynamic range of the sensor. Because of their virtually identical spectral properties, various PBIs with selected PET functions can easily be integrated into a single sensor with enlarged dynamic range (over 4 pH units). PBIs with two different substitution patterns in the bay position are investigated and possess variable spectral properties. Compared with their tetrachloro analogues, tetra-tert-butyl-substituted PBIs yield more long-wave excitable sensors which feature excellent photostability. Cross-sensitivity to ionic strength was found to be negligible. The practical applicability of the sensors may be compromised by the long response times (especially in case of tetra-tert-butyl-substituted PBIs).

Understanding the context for pet cat and dog feeding and exercising behaviour among pet owners in Ireland: a qualitative study.

PubMed

Downes, Martin J; Devitt, Catherine; Downes, Marie T; More, Simon J

2017-01-01

Pet cat and dog obesity contributes to increased risk of several diseases, including cancer and diabetes mellitus as well as a worsening of orthopaedic problems, and a reduction in survival rate. This study aims to develop a better understanding of cat and dog owners' self-reported beliefs and factors that influence owner behaviour around feeding and exercising their pet cat or dog, as there is a lack of in-depth understanding in this area. Seven focus group discussions, with 43 pet owners in total, were conducted. Pet owners often reported a perceived a low level of control over feeding; often undermined by other people feeding of their pet, their pets begging for food, and their pets attitude towards food. Treats were used in the absence of owner control over pet begging and emotional attachment, and to influence pet behaviour. The majority of participants had positive attitudes to pet exercise, which could be related to pet specific requirements, especially differences in cats and dogs. There were some negative experiences of stress associated with dog walking and fears over aggressive confrontations with other dogs. Feeding one's pet is influenced by beliefs about pet specific needs, pet food and pet health, pet owners' perceived control over feeding, and the implications for the pet owner. Pet exercise is influenced by beliefs about pet specific exercise needs, and the implications of exercising one's pet for the pet owner. Understanding owner behaviours on feeding and exercise allows for a more targeted approach to preventing and treating pet obesity.

Evaluation of PET Scanner Performance in PET/MR and PET/CT Systems: NEMA Tests.

PubMed

Demir, Mustafa; Toklu, Türkay; Abuqbeitah, Mohammad; Çetin, Hüseyin; Sezgin, H Sezer; Yeyin, Nami; Sönmezoğlu, Kerim

2018-02-01

The aim of the present study was to compare the performance of positron emission tomography (PET) component of PET/computed tomography (CT) with new emerging PET/magnetic resonance (MR) of the same vendor. According to National Electrical Manufacturers Association NU2-07, five separate experimental tests were performed to evaluate the performance of PET scanner of General Electric GE company; SIGNATM model PET/MR and GE Discovery 710 model PET/CT. The main investigated aspects were spatial resolution, sensitivity, scatter fraction, count rate performance, image quality, count loss and random events correction accuracy. The findings of this study demonstrated superior sensitivity (~ 4 folds) of PET scanner in PET/MR compared to PET/CT system. Image quality test exhibited higher contrast in PET/MR (~ 9%) compared with PET/CT. The scatter fraction of PET/MR was 43.4% at noise equivalent count rate (NECR) peak of 218 kcps and the corresponding activity concentration was 17.7 kBq/cc. Whereas the scatter fraction of PET/CT was found as 39.2% at NECR peak of 72 kcps and activity concentration of 24.3 kBq/cc. The percentage error of the random event correction accuracy was 3.4% and 3.1% in PET/MR and PET/CT, respectively. It was concluded that PET/MR system is about 4 times more sensitive than PET/CT, and the contrast of hot lesions in PET/MR was ~ 9% higher than PET/CT. These outcomes also emphasize the possibility to achieve excellent clinical PET images with low administered dose and/or a short acquisition time in PET/MR.

Preclinical Evaluation of 18F-JNJ64349311, a Novel PET Tracer for Tau Imaging.

PubMed

Declercq, Lieven; Rombouts, Frederik; Koole, Michel; Fierens, Katleen; Mariën, Jonas; Langlois, Xavier; Andrés, José Ignacio; Schmidt, Mark; Macdonald, Gregor; Moechars, Diederik; Vanduffel, Wim; Tousseyn, Thomas; Vandenberghe, Rik; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

2017-06-01

In this study, we have synthesized and evaluated 18 F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500×) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18 F-AV1451 ( 18 F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18 F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ∼1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time-activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18 F-JNJ64349311 is a promising tau PET tracer candidate, with a favorable pharmacokinetic profile, as compared with 18 F-AV1451. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Comparison of 18F-FDG PET/CT and PET/MRI in patients with multiple myeloma

PubMed Central

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Mosebach, Jennifer; Pan, Leyun; Schlemmer, Heinz-Peter; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

PET/MRI represents a promising hybrid imaging modality with several potential clinical applications. Although PET/MRI seems highly attractive in the diagnostic approach of multiple myeloma (MM), its role has not yet been evaluated. The aims of this prospective study are to evaluate the feasibility of 18F-FDG PET/MRI in detection of MM lesions, and to investigate the reproducibility of bone marrow lesions detection and quantitative data of 18F-FDG uptake between the functional (PET) component of PET/CT and PET/MRI in MM patients. The study includes 30 MM patients. All patients initially underwent 18F-FDG PET/CT (60 min p.i.), followed by PET/MRI (120 min p.i.). PET/CT and PET/MRI data were assessed and compared based on qualitative (lesion detection) and quantitative (SUV) evaluation. The hybrid PET/MRI system provided good image quality in all cases without artefacts. PET/MRI identified 65 of the 69 lesions, which were detectable with PET/CT (94.2%). Quantitative PET evaluations showed the following mean values in MM lesions: SUVaverage=5.5 and SUVmax=7.9 for PET/CT; SUVaverage=3.9 and SUVmax=5.8 for PET/MRI. Both SUVaverage and SUVmax were significantly higher on PET/CT than on PET/MRI. Spearman correlation analysis demonstrated a strong correlation between both lesional SUVaverage (r=0.744) and lesional SUVmax (r=0.855) values derived from PET/CT and PET/MRI. Regarding detection of myeloma skeletal lesions, PET/MRI exhibited equivalent performance to PET/CT. In terms of tracer uptake quantitation, a significant correlation between the two techniques was demonstrated, despite the statistically significant differences in lesional SUVs between PET/CT and PET/MRI. PMID:26550538

Monitoring early response to chemoradiotherapy with 18F-FMISO dynamic PET in head and neck cancer.

PubMed

Grkovski, Milan; Lee, Nancy Y; Schöder, Heiko; Carlin, Sean D; Beattie, Bradley J; Riaz, Nadeem; Leeman, Jonathan E; O'Donoghue, Joseph A; Humm, John L

2017-09-01

There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of 18 F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC. Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy. Voxelwise pharmacokinetic modeling was conducted using an irreversible one-plasma two-tissue compartment model to calculate surrogate biomarkers of tumor hypoxia (k 3 and Tumor-to-Blood Ratio (TBR)), perfusion (K 1 ) and FMISO distribution volume (DV). Additionally, Tumor-to-Muscle Ratios (TMR) were derived by visual inspection by an experienced nuclear medicine physician, with TMR > 1.2 defining hypoxia. One hundred and thirty-five lesions in total were analyzed. TBR, k 3 and DV decreased on early response scans, while no significant change was observed for K 1 . The k 3 -TBR correlation decreased substantially from baseline scans (Pearson's r = 0.72 and 0.76 for mean intratumor and pooled voxelwise values, respectively) to early response scans (Pearson's r = 0.39 and 0.40, respectively). Both concordant and discordant examples of changes in intratumor k 3 and TBR were identified; the latter partially mediated by the change in DV. In 13 normoxic patients according to visual analysis (all having lesions with TMR = 1.2), subvolumes were identified where k 3 indicated the presence of hypoxia. Pharmacokinetic modeling of FMISO dynamic PET reveals a more detailed characterization of the tumor microenvironment and assessment of response to chemoradiotherapy in HNC patients than a single static image does. In a clinical trial where absence of hypoxia in primary tumor and lymph nodes would lead to de-escalation of therapy, the observed disagreement between visual analysis and pharmacokinetic modeling results would have affected patient management in <20% cases. While simple static PET imaging is easily implemented for clinical trials, the clinical applicability of pharmacokinetic modeling remains to be investigated.

The role of PET quantification in cardiovascular imaging.

PubMed

Slomka, Piotr; Berman, Daniel S; Alexanderson, Erick; Germano, Guido

2014-08-01

Positron Emission Tomography (PET) has several clinical and research applications in cardiovascular imaging. Myocardial perfusion imaging with PET allows accurate global and regional measurements of myocardial perfusion, myocardial blood flow and function at stress and rest in one exam. Simultaneous assessment of function and perfusion by PET with quantitative software is currently the routine practice. Combination of ejection fraction reserve with perfusion information may improve the identification of severe disease. The myocardial viability can be estimated by quantitative comparison of fluorodeoxyglucose ( 18 FDG) and rest perfusion imaging. The myocardial blood flow and coronary flow reserve measurements are becoming routinely included in the clinical assessment due to enhanced dynamic imaging capabilities of the latest PET/CT scanners. Absolute flow measurements allow evaluation of the coronary microvascular dysfunction and provide additional prognostic and diagnostic information for coronary disease. Standard quantitative approaches to compute myocardial blood flow from kinetic PET data in automated and rapid fashion have been developed for 13 N-ammonia, 15 O-water and 82 Rb radiotracers. The agreement between software methods available for such analysis is excellent. Relative quantification of 82 Rb PET myocardial perfusion, based on comparisons to normal databases, demonstrates high performance for the detection of obstructive coronary disease. New tracers, such as 18 F-flurpiridaz may allow further improvements in the disease detection. Computerized analysis of perfusion at stress and rest reduces the variability of the assessment as compared to visual analysis. PET quantification can be enhanced by precise coregistration with CT angiography. In emerging clinical applications, the potential to identify vulnerable plaques by quantification of atherosclerotic plaque uptake of 18 FDG and 18 F-sodium fluoride tracers in carotids, aorta and coronary arteries has been demonstrated.

A Conway-Maxwell-Poisson (CMP) model to address data dispersion on positron emission tomography.

PubMed

Santarelli, Maria Filomena; Della Latta, Daniele; Scipioni, Michele; Positano, Vincenzo; Landini, Luigi

2016-10-01

Positron emission tomography (PET) in medicine exploits the properties of positron-emitting unstable nuclei. The pairs of γ- rays emitted after annihilation are revealed by coincidence detectors and stored as projections in a sinogram. It is well known that radioactive decay follows a Poisson distribution; however, deviation from Poisson statistics occurs on PET projection data prior to reconstruction due to physical effects, measurement errors, correction of deadtime, scatter, and random coincidences. A model that describes the statistical behavior of measured and corrected PET data can aid in understanding the statistical nature of the data: it is a prerequisite to develop efficient reconstruction and processing methods and to reduce noise. The deviation from Poisson statistics in PET data could be described by the Conway-Maxwell-Poisson (CMP) distribution model, which is characterized by the centring parameter λ and the dispersion parameter ν, the latter quantifying the deviation from a Poisson distribution model. In particular, the parameter ν allows quantifying over-dispersion (ν<1) or under-dispersion (ν>1) of data. A simple and efficient method for λ and ν parameters estimation is introduced and assessed using Monte Carlo simulation for a wide range of activity values. The application of the method to simulated and experimental PET phantom data demonstrated that the CMP distribution parameters could detect deviation from the Poisson distribution both in raw and corrected PET data. It may be usefully implemented in image reconstruction algorithms and quantitative PET data analysis, especially in low counting emission data, as in dynamic PET data, where the method demonstrated the best accuracy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma.

PubMed

Quartuccio, Natale; Treglia, Giorgio; Salsano, Marco; Mattoli, Maria Vittoria; Muoio, Barbara; Piccardo, Arnoldo; Lopci, Egesta; Cistaro, Angelina

2013-06-01

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS). A comprehensive literature search of published studies through October 10(th), 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed. We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS. Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning.

[Microeconomics of introduction of a PET system based on the revised Japanese National Insurance reimbursement system].

PubMed

Abe, Katsumi; Kosuda, Shigeru; Kusano, Shoichi; Nagata, Masayoshi

2003-11-01

It is crucial to evaluate an annual balance before-hand when an institution installs a PET system because the revised Japanese national insurance reimbursement system set the cost of a FDG PET study as 75,000 yen. A break-even point was calculated in an 8-hour or a 24-hour operation of a PET system, based on the total costs reported. The break-even points were as follows: 13.4, 17.7, 22.1 studies per day for the 1 cyclotron-1 PET camera, 1 cyclotron-2 PET cameras, 1 cyclotron-3 PET cameras system, respectively, in an ordinary PET system operation of 8 hours. The break-even points were 19.9, 25.5, 31.2 studies per day for the 1 cyclotron-1 PET camera, 1 cyclotron-2 PET cameras, 1 cyclotron-3 PET cameras system, respectively, in a full PET system operation of 24 hours. The results indicate no profit would accrue in an ordinary PET system operation of 8 hours. The annual profit and break-even point for the total cost including the initial investment would be respectively 530 million yen and 2.8 years in a 24-hour operation with 1 cyclotron-3 PET cameras system.

Cardiac-gated parametric images from 82 Rb PET from dynamic frames and direct 4D reconstruction.

PubMed

Germino, Mary; Carson, Richard E

2018-02-01

Cardiac perfusion PET data can be reconstructed as a dynamic sequence and kinetic modeling performed to quantify myocardial blood flow, or reconstructed as static gated images to quantify function. Parametric images from dynamic PET are conventionally not gated, to allow use of all events with lower noise. An alternative method for dynamic PET is to incorporate the kinetic model into the reconstruction algorithm itself, bypassing the generation of a time series of emission images and directly producing parametric images. So-called "direct reconstruction" can produce parametric images with lower noise than the conventional method because the noise distribution is more easily modeled in projection space than in image space. In this work, we develop direct reconstruction of cardiac-gated parametric images for 82 Rb PET with an extension of the Parametric Motion compensation OSEM List mode Algorithm for Resolution-recovery reconstruction for the one tissue model (PMOLAR-1T). PMOLAR-1T was extended to accommodate model terms to account for spillover from the left and right ventricles into the myocardium. The algorithm was evaluated on a 4D simulated 82 Rb dataset, including a perfusion defect, as well as a human 82 Rb list mode acquisition. The simulated list mode was subsampled into replicates, each with counts comparable to one gate of a gated acquisition. Parametric images were produced by the indirect (separate reconstructions and modeling) and direct methods for each of eight low-count and eight normal-count replicates of the simulated data, and each of eight cardiac gates for the human data. For the direct method, two initialization schemes were tested: uniform initialization, and initialization with the filtered iteration 1 result of the indirect method. For the human dataset, event-by-event respiratory motion compensation was included. The indirect and direct methods were compared for the simulated dataset in terms of bias and coefficient of variation as a function of iteration. Convergence of direct reconstruction was slow with uniform initialization; lower bias was achieved in fewer iterations by initializing with the filtered indirect iteration 1 images. For most parameters and regions evaluated, the direct method achieved the same or lower absolute bias at matched iteration as the indirect method, with 23%-65% lower noise. Additionally, the direct method gave better contrast between the perfusion defect and surrounding normal tissue than the indirect method. Gated parametric images from the human dataset had comparable relative performance of indirect and direct, in terms of mean parameter values per iteration. Changes in myocardial wall thickness and blood pool size across gates were readily visible in the gated parametric images, with higher contrast between myocardium and left ventricle blood pool in parametric images than gated SUV images. Direct reconstruction can produce parametric images with less noise than the indirect method, opening the potential utility of gated parametric imaging for perfusion PET. © 2017 American Association of Physicists in Medicine.

A PET Tracer for Renal Organic Cation Transporters, ¹¹C-Metformin: Radiosynthesis and Preclinical Proof-of-Concept Studies.

PubMed

Jakobsen, Steen; Busk, Morten; Jensen, Jonas Brorson; Munk, Ole Lajord; Zois, Nora Elisabeth; Alstrup, Aage K O; Jessen, Niels; Frøkiær, Jørgen

2016-04-01

Organic cation transporters (OCTs) in the kidney proximal tubule (PT) participate in renal excretion of drugs and endogenous compounds. PT function is commonly impaired in kidney diseases, and consequently quantitative measurement of OCT function may provide an important estimate of kidney function. Metformin is a widely used drug and targets OCT type 2 located in the PT. Thus, we hypothesized that (11)C-labeled metformin would be a suitable PET tracer for quantification of renal function. (11)C-metformin was prepared by (11)C-methylation of 1-methylbiguanide. In vitro cell uptake of (11)C-metformin was studied in LLC-PK1 cells in the presence of increasing doses of unlabeled metformin. In vivo small-animal PET studies in Sprague-Dawley rats were performed at baseline and after treatment with OCT inhibitors to evaluate renal uptake of (11)C-metformin. Kidney and liver pharmacokinetics of (11)C-metformin was investigated in vivo by dynamic (11)C-metformin PET/CT in 6 anesthetized pigs, and renal clearance of (11)C-metformin was compared with renal clearance of (51)Cr-ethylenediaminetetraacetic acid (EDTA). Formation of (11)C metabolites was investigated by analysis of blood and urine samples. The radiochemical yield of (11)C-metformin was 15% ± 3% (n= 40, decay-corrected), and up to 1.5 GBq of tracer were produced with a radiochemical purity greater than 95% in less than 30 min. Dose-dependent uptake of (11)C-metformin in LLC-PK1 cells was rapid. Rat small-animal PET images showed (11)C-metformin uptake in the kidney and liver, the kinetics of which were changed after challenging animals with OCT inhibitors. In pigs, 80% of the injected metformin dose was rapidly present in the kidney, and a high dose of metformin caused a delayed renal uptake and clearance compared with baseline consistent with transporter-mediated competition. Renal clearance of (11)C-metformin was approximately 3 times the renal clearance of (51)Cr-EDTA. We successfully synthesized an (11)C-metformin tracer, and PET studies in rats and pigs showed a rapid kidney uptake from the blood and excretion into the bladder similar to other radiopharmaceuticals developed for γ-camera renography. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Quantification of myocardial blood flow with dynamic perfusion 3.0 Tesla MRI: Validation with (15) O-water PET.

PubMed

Tomiyama, Yuuki; Manabe, Osamu; Oyama-Manabe, Noriko; Naya, Masanao; Sugimori, Hiroyuki; Hirata, Kenji; Mori, Yuki; Tsutsui, Hiroyuki; Kudo, Kohsuke; Tamaki, Nagara; Katoh, Chietsugu

2015-09-01

To develop and validate a method for quantifying myocardial blood flow (MBF) using dynamic perfusion magnetic resonance imaging (MBFMRI ) at 3.0 Tesla (T) and compare the findings with those of (15) O-water positron emission tomography (MBFPET ). Twenty healthy male volunteers underwent magnetic resonance imaging (MRI) and (15) O-water positron emission tomography (PET) at rest and during adenosine triphosphate infusion. The single-tissue compartment model was used to estimate the inflow rate constant (K1). We estimated the extraction fraction of Gd-DTPA using K1 and MBF values obtained from (15) O-water PET for the first 10 subjects. For validation, we calculated MBFMRI values for the remaining 10 subjects and compared them with the MBFPET values. In addition, we compared MBFMRI values of 10 patients with coronary artery disease with those of healthy subjects. The mean resting and stress MBFMRI values were 0.76 ± 0.10 and 3.04 ± 0.82 mL/min/g, respectively, and showed excellent correlation with the mean MBFPET values (r = 0.96, P < 0.01). The mean stress MBFMRI value was significantly lower for the patients (1.92 ± 0.37) than for the healthy subjects (P < 0.001). The use of dynamic perfusion MRI at 3T is useful for estimating MBF and can be applied for patients with coronary artery disease. © 2014 Wiley Periodicals, Inc.

Prevalence and malignancy risk of focal colorectal incidental uptake detected by (18)F-FDG-PET or PET/CT: a meta-analysis.

PubMed

Treglia, Giorgio; Taralli, Silvia; Salsano, Marco; Muoio, Barbara; Sadeghi, Ramin; Giovanella, Luca

2014-06-01

The aim of the study was to meta-analyze published data about prevalence and malignancy risk of focal colorectal incidentalomas (FCIs) detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography ((18)F-FDG-PET or PET/CT). A comprehensive computer literature search of studies published through July 31(st) 2012 regarding FCIs detected by (18)F-FDG-PET or PET/CT was performed. Pooled prevalence of patients with FCIs and risk of malignant or premalignant FCIs after colonoscopy or histopathology verification were calculated. Furthermore, separate calculations for geographic areas were performed. Finally, average standardized uptake values (SUV) in malignant, premalignant and benign FCIs were reported. Thirty-two studies comprising 89,061 patients evaluated by (18)F-FDG-PET or PET/CT were included. The pooled prevalence of FCIs detected by (18)F-FDG-PET or PET/CT was 3.6% (95% confidence interval [95% CI]: 2.6-4.7%). Overall, 1,044 FCIs detected by (18)F-FDG-PET or PET/CT underwent colonoscopy or histopathology evaluation. Pooled risk of malignant or premalignant lesions was 68% (95% CI: 60-75%). Risk of malignant and premalignant FCIs in Asia-Oceania was lower compared to that of Europe and America. A significant overlap in average SUV was found between malignant, premalignant and benign FCIs. FCIs are observed in a not negligible number of patients who undergo (18)F-FDG-PET or PET/CT studies with a high risk of malignant or premalignant lesions. SUV is not reliable as a tool to differentiate between malignant, premalignant and benign FCIs. Further investigation is warranted whenever FCIs are detected by (18)F-FDG-PET or PET/CT.

Prevalence and malignancy risk of focal colorectal incidental uptake detected by 18F-FDG-PET or PET/CT: a meta-analysis

PubMed Central

Treglia, Giorgio; Taralli, Silvia; Salsano, Marco; Muoio, Barbara; Sadeghi, Ramin; Giovanella, Luca

2014-01-01

Background The aim of the study was to meta-analyze published data about prevalence and malignancy risk of focal colorectal incidentalomas (FCIs) detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (18F-FDG-PET or PET/CT). Methods A comprehensive computer literature search of studies published through July 31st 2012 regarding FCIs detected by 18F-FDG-PET or PET/CT was performed. Pooled prevalence of patients with FCIs and risk of malignant or premalignant FCIs after colonoscopy or histopathology verification were calculated. Furthermore, separate calculations for geographic areas were performed. Finally, average standardized uptake values (SUV) in malignant, premalignant and benign FCIs were reported. Results Thirty-two studies comprising 89,061 patients evaluated by 18F-FDG-PET or PET/CT were included. The pooled prevalence of FCIs detected by 18F-FDG-PET or PET/CT was 3.6% (95% confidence interval [95% CI]: 2.6–4.7%). Overall, 1,044 FCIs detected by 18F-FDG-PET or PET/CT underwent colonoscopy or histopathology evaluation. Pooled risk of malignant or premalignant lesions was 68% (95% CI: 60–75%). Risk of malignant and premalignant FCIs in Asia-Oceania was lower compared to that of Europe and America. A significant overlap in average SUV was found between malignant, premalignant and benign FCIs. Conclusions FCIs are observed in a not negligible number of patients who undergo 18F-FDG-PET or PET/CT studies with a high risk of malignant or premalignant lesions. SUV is not reliable as a tool to differentiate between malignant, premalignant and benign FCIs. Further investigation is warranted whenever FCIs are detected by 18F-FDG-PET or PET/CT. PMID:24991198

Tumor Metabolism and Perfusion in Head and Neck Squamous Cell Carcinoma: Pretreatment Multimodality Imaging With {sup 1}H Magnetic Resonance Spectroscopy, Dynamic Contrast-Enhanced MRI, and [{sup 18}F]FDG-PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jansen, Jacobus F.A.; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Radiology, Maastricht University Medical Center, Maastricht

2012-01-01

Purpose: To correlate proton magnetic resonance spectroscopy ({sup 1}H-MRS), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and {sup 18}F-labeled fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG PET) of nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging was evaluated for its efficacy in predicting short-term response to treatment. Methods and Materials: Metastatic neck nodes were imaged with {sup 1}H-MRS, DCE-MRI, and [{sup 18}F]FDG PET in 16 patients with newly diagnosed HNSCC, before treatment. Short-term patient radiological response was evaluated at 3 to 4 months. Correlations among {sup 1}H-MRS (choline concentrationmore » relative to water [Cho/W]), DCE-MRI (volume transfer constant [K{sup trans}]; volume fraction of the extravascular extracellular space [v{sub e}]; and redistribution rate constant [k{sub ep}]), and [{sup 18}F]FDG PET (standard uptake value [SUV] and total lesion glycolysis [TLG]) were calculated using nonparametric Spearman rank correlation. To predict short-term responses, logistic regression analysis was performed. Results: A significant positive correlation was found between Cho/W and TLG ({rho} = 0.599; p = 0.031). Cho/W correlated negatively with heterogeneity measures of standard deviation std(v{sub e}) ({rho} = -0.691; p = 0.004) and std(k{sub ep}) ({rho} = -0.704; p = 0.003). Maximum SUV (SUVmax) values correlated strongly with MRI tumor volume ({rho} = 0.643; p = 0.007). Logistic regression indicated that std(K{sup trans}) and SUVmean were significant predictors of short-term response (p < 0.07). Conclusion: Pretreatment multimodality imaging using {sup 1}H-MRS, DCE-MRI, and [{sup 18}F]FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and [{sup 18}F]FDG PET parameters were predictive of short-term response to treatment.« less

Pet ownership and adolescent health: cross-sectional population study.

PubMed

Mathers, Megan; Canterford, Louise; Olds, Tim; Waters, Elizabeth; Wake, Melissa

2010-12-01

To determine whether adolescent health and well-being are associated with having a pet in the household (any pet, or specifically dogs, cats or horses/ponies) or average daily time spent caring for/playing with pet(s). Design, setting and participants--Cross-sectional data from the third wave of the Health of Young Victorians Study (HOYVS), a school-based population study in Victoria, Australia. Predictors--Adolescent-reported pet ownership and average daily time spent caring for/playing with pet(s). Outcomes--Self-reported quality of life (KIDSCREEN); average 4-day daily physical activity level from a computerised diary; parent-proxy and self-reported physical and psychosocial health status (PedsQL); measured BMI status (not overweight, overweight, obese) and blood pressure. Statistical Analysis--Regression methods, adjusted for socio-demographic factors, and non-parametric methods. Household pet data were available for 928 adolescents (466 boys; mean age of 15.9 (SD 1.2) years). Most adolescents (88.7%) reported having a pet in their household. Of these, 75.1% reported no activity involving pets over the surveyed days. It appeared that neither owning a pet nor time spent caring for/playing with a pet was related, positively or negatively, to adolescent health or well-being. Despite high rates of pet ownership, adolescents had little interaction with pets. It appears that owning a pet and time spent caring for/playing with a pet was not clearly associated with adolescents' health or well-being. © 2010 The Authors. Journal of Paediatrics and Child Health © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Simulation of tissue activity curves of 64Cu-ATSM for sub-target volume delineation in radiotherapy

NASA Astrophysics Data System (ADS)

Dalah, E.; Bradley, D.; Nisbet, A.

2010-02-01

There is much interest in positron emission tomography (PET) for measurements of regional tracer concentration in hypoxic tumour-bearing tissue, focusing on the need for accurate radiotherapy treatment planning. Generally, relevant data are taken over multiple time frames in the form of tissue activity curves (TACs), thus providing an indication of vasculature structure and geometry. This is a potential key in providing information on cellular perfusion and limited diffusion. A number of theoretical studies have attempted to describe tracer uptake in tissue cells in an effort to understand such complicated behaviour of cellular uptake and the mechanism of washout. More recently, a novel computerized reaction diffusion equation method was developed by Kelly and Brady (2006 A model to simulate tumour oxygenation and dynamic [18F]-FMISO PET data Phys. Med. Biol. 51 5859-73), where they managed to simulate the realistic dynamic TACs of 18F-FMISO. The model was developed over a multi-step process. Here we present a refinement to the work of Kelly and Brady, such that the model allows simulation of a realistic tissue activity curve (TAC) of any hypoxia selective PET tracer, in a single step process. In this work we show particular interest in simulating the TAC of perhaps the most promising hypoxia selective tracer, 64Cu-ATSM. In addition, we demonstrate its potential role in tumour sub-volume delineation for radiotherapy treatment planning. Simulation results have demonstrated the significant high contrast of imaging using ATSM, with a tumour to blood ratio ranging from 2.24 to 4.1.

Multimodal correlation of dynamic [18F]-AV-1451 perfusion PET and neuronal hypometabolism in [18F]-FDG PET.

PubMed

Hammes, Jochen; Leuwer, Isabel; Bischof, Gérard N; Drzezga, Alexander; van Eimeren, Thilo

2017-12-01

Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury. Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls. Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar. Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

Technical requirements for Na¹⁸F PET bone imaging of patients being treated using a Taylor spatial frame.

PubMed

Hatherly, Robert; Brolin, Fredrik; Oldner, Åsa; Sundin, Anders; Lundblad, Henrik; Maguire, Gerald Q; Jonsson, Cathrine; Jacobsson, Hans; Noz, Marilyn E

2014-03-01

Diagnosis of new bone growth in patients with compound tibia fractures or deformities treated using a Taylor spatial frame is difficult with conventional radiography because the frame obstructs the images and creates artifacts. The use of Na(18)F PET studies may help to eliminate this difficulty. Patients were positioned on the pallet of a clinical PET/CT scanner and made as comfortable as possible with their legs immobilized. One bed position covering the site of the fracture, including the Taylor spatial frame, was chosen for the study. A topogram was performed, as well as diagnostic and attenuation correction CT. The patients were given 2 MBq of Na(18)F per kilogram of body weight. A 45-min list-mode acquisition was performed starting at the time of injection, followed by a 5-min static acquisition 60 min after injection. The patients were examined 6 wk after the Taylor spatial frame had been applied and again at 3 mo to assess new bone growth. A list-mode reconstruction sequence of 1 × 1,800 and 1 × 2,700 s, as well as the 5-min static scan, allowed visualization of regional bone turnover. With Na(18)F PET/CT, it was possible to confirm regional bone turnover as a means of visualizing bone remodeling without the interference of artifacts from the Taylor spatial frame. Furthermore, dynamic list-mode acquisition allowed different sequences to be performed, enabling, for example, visualization of tracer transport from blood to the fracture site.

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeGrado, Timothy R.; Kemp, Bradley J.; Pandey, Mukesh K.

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. A dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (~330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B ( 11C-PiB) andmore » 18F-fluorodeoxyglucose ( 18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.« less

Myocardial blood flow quantification by Rb-82 cardiac PET/CT: A detailed reproducibility study between two semi-automatic analysis programs.

PubMed

Dunet, Vincent; Klein, Ran; Allenbach, Gilles; Renaud, Jennifer; deKemp, Robert A; Prior, John O

2016-06-01

Several analysis software packages for myocardial blood flow (MBF) quantification from cardiac PET studies exist, but they have not been compared using concordance analysis, which can characterize precision and bias separately. Reproducible measurements are needed for quantification to fully develop its clinical potential. Fifty-one patients underwent dynamic Rb-82 PET at rest and during adenosine stress. Data were processed with PMOD and FlowQuant (Lortie model). MBF and myocardial flow reserve (MFR) polar maps were quantified and analyzed using a 17-segment model. Comparisons used Pearson's correlation ρ (measuring precision), Bland and Altman limit-of-agreement and Lin's concordance correlation ρc = ρ·C b (C b measuring systematic bias). Lin's concordance and Pearson's correlation values were very similar, suggesting no systematic bias between software packages with an excellent precision ρ for MBF (ρ = 0.97, ρc = 0.96, C b = 0.99) and good precision for MFR (ρ = 0.83, ρc = 0.76, C b = 0.92). On a per-segment basis, no mean bias was observed on Bland-Altman plots, although PMOD provided slightly higher values than FlowQuant at higher MBF and MFR values (P < .0001). Concordance between software packages was excellent for MBF and MFR, despite higher values by PMOD at higher MBF values. Both software packages can be used interchangeably for quantification in daily practice of Rb-82 cardiac PET.

Approaches using molecular imaging technology - use of PET in clinical microdose studies§

PubMed Central

Wagner, Claudia C; Langer, Oliver

2013-01-01

Positron emission tomography (PET) imaging uses minute amounts of radiolabeled drug tracers and thereby meets the criteria for clinical microdose studies. The advantage of PET, when compared to other analytical methods used in microdose studies, is that the pharmacokinetics (PK) of a drug can be determined in the tissue targeted for drug treatment. PET microdosing already offers interesting applications in clinical oncology and in the development of central nervous system pharmaceuticals and is extending its range of application to many other fields of pharmaceutical medicine. Although requirements for preclinical safety testing for microdose studies have been cut down by regulatory authorities, radiopharmaceuticals increasingly need to be produced under good manufacturing practice (GMP) conditions, which increases the costs of PET microdosing studies. Further challenges in PET microdosing include combining PET with other ultrasensitive analytical methods, such as accelerator mass spectrometry (AMS), to gain plasma PK data of drugs, beyond the short PET examination periods. Finally, conducting clinical PET studies with radiolabeled drugs both at micro- and therapeutic doses is encouraged to answer the question of dose linearity in clinical microdosing. PMID:20887762

Quantitative analysis of binding sites for 9-fluoropropyl-(+)-dihydrotetrabenazine ([¹⁸F]AV-133) in a MPTP-lesioned PD mouse model.

PubMed

Chao, Ko-Ting; Tsao, Hsin-Hsin; Weng, Yi-Hsin; Hsiao, Ing-Tsung; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Kung, Mei-Ping; Lin, Kun-Ju

2012-09-01

[¹⁸F]AV-133 is a novel PET tracer for targeting the vesicular monoamine transporter 2 (VMAT2). The aim of this study is to characterize and quantify the loss of monoamine neurons with [¹⁸F]AV-133 in the MPTP-lesioned PD mouse model using animal PET imaging and ex vivo quantitative autoradiography (QARG). Optimal imaging time window of [¹⁸F]AV-133 was first determined in normal C57BL/6 mice (n = 3) with a 90-min dynamic scan. The reproducibility of [¹⁸F]AV-133 PET imaging was evaluated by performing a test-retest study within 1 week for the normal group (n = 6). For MPTP-lesioned studies, normal, and MPTP-treated [25 mg mg/kg once (Group A) and twice (Group B), respectively, daily for 5 days, i.p., groups of four normal and MPTP-treated] mice were used. PET imaging studies at baseline and at Day 4 post-MPTP injections were performed at the optimal time window after injection of 11.1 MBq [¹⁸F]AV-133. Specific uptake ratio (SUr) of [¹⁸F]AV-133 was calculated by [(target uptake-cerebellar uptake)/cerebellar uptake] with cerebellum as the reference region. Ex vitro QARG and immunohistochemistry (IHC) studies with tyrosine hydroxylase antibody were carried out to confirm the abundance of dopaminergic neurons. The variability between [¹⁸F]AV-133 test-retest striatal SUr was 6.60 ± 3.61% with less than 5% standard deviation between animals (intervariability). The percentages of MPTP lesions were Group A 0.94 ± 0.29, -42.1% and Group B 0.65 ± 0.09, -60.4%. By QARG, specific binding of [¹⁸F]AV-133 was reduced relative to the control groups by 50.6% and 60.7% in striatum and by 30.6% and 46.4% in substantia nigra (Groups A and B, respectively). Relatively small [¹⁸F]AV-133 SUr decline was noted in the serotonin and norepinephrine-enriched regions (7.9% and 9.4% in mid-brain). Results obtained from IHC consistently confirmed the sensitivity and selectivity of dopaminergic neuron loss after MPTP treatment. [¹⁸F]AV-133 PET SUr displayed a high test-retest stability. The SUr significantly declined in the caudate putamen but not in the hypothalamus and midbrain regions after MPTP treatment in the mouse brain. The results obtained for QARG and IHC were consistent and correlated well with the PET imaging studies. On the basis of these concordant results, we find that [¹⁸F]AV-133 should serve as a useful and reliable PET tracer for evaluating nigrostriatal degeneration. Copyright © 2012 Wiley Periodicals, Inc.

Development of a Body Shield for Small Animal PET System to Reduce Random and Scatter Coincidences

NASA Astrophysics Data System (ADS)

Wada, Yasuhiro; Yamamoto, Seiichi; Watanabe, Yasuyoshi

2015-02-01

For small animal positron emission tomography (PET) research using high radioactivity, such as dynamic studies, the resulting high random coincidence rate of the system degrades image quality. The random coincidence rate is increased not only by the gamma photons from inside the axial-field-of-view (axial-FOV) of the PET system but also by those from outside the axial-FOV. For brain imaging in small animal studies, significant interference is observed from gamma photons emitted from the body. Single gamma photons from the body enter the axial-FOV and increase the random and scatter coincidences. Shielding against the gamma photons from outside the axial-FOV would improve the image quality. For this purpose, we developed a body shield for a small animal PET system, the microPET Primate 4-ring system, and evaluated its performance. The body shield is made of 9-mm-thick lead and it surrounds most of a rat's body. We evaluated the effectiveness of the body shield using a head phantom and a body phantom with a radioactivity concentration ratio of 1:2 and a maximum total activity of approximately 250 MBq. The random coincidence rate was dramatically decreased to 1/10, and the noise equivalent count rate (NECR) was increased 6 times with an activity of 7 MBq in the head phantom. The true count rate was increased to 35% due to the decrease in system deadtime. The average scatter fraction was decreased to 1/2.5 with the body shield. Count rate measurements of rat were also conducted with an injection activity of approximately 25 MBq of [C-11]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([C-11]DASB) and approximately 70 and 310 MBq of 2-deoxy-2-(F-18)fluoro-D-glucose ([F-18]FDG). Using the body shield, [F-18]FDG images of rats were improved by increasing the amount of radioactivity injected. The body shield designed for small animal PET systems is a promising tool for improving image quality and quantitation accuracy in small animal molecular imaging research.

Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies.

PubMed

Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Nariai, Tadashi; Ishiwata, Kiichi

2013-04-01

We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.

Melt rheological properties of nucleated PET/MWCNT nanocomposites

NASA Astrophysics Data System (ADS)

Gaonkar, Amita; Murudkar, Vrishali; Deshpande, V. D.

2018-05-01

This work investigates the effect of precipitated Polyethylene Terephthalate (p-PET) and loading of Multiwalled carbon nanotubes (MWCNT) on morphology and rheology of Polyethylene Terephthalate (PET)/MWCNT nanocomposites. As received PET and Self-Nucleated PET (Nuc-PET) nanocomposites with different loadings of multi-walled carbon nanotubes (MWCNT) were prepared by melt mixing technique. Synthesized reorganized PET crystallizes rapidly from the melt and it is used in small quantities as a self-nucleating agent to make Nuc-PET. In the present study, Rheological properties of nanocomposites are obtained and results show with increase in MWCNT loading complex viscosity of nanocomposites increases. Nonterminal solid like rheological behavior of PET nanocomposites were observed at low frequencies, which indicates the formation of the network like structures of MWCNT in nanocomposites. Morphological and rheological properties of self-nucleated PET nanocomposites improved significantly may be due to self-nucleating agent p-PET. Morphological properties were studied by Scanning Electron Microscopy (SEM). SEM shows better dispersion of MWCNT in Nuc-PET nanocomposites.

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma

PubMed Central

Quartuccio, Natale; Treglia, Giorgio; Salsano, Marco; Mattoli, Maria Vittoria; Muoio, Barbara; Piccardo, Arnoldo; Lopci, Egesta; Cistaro, Angelina

2013-01-01

Background The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS). Methods A comprehensive literature search of published studies through October 10th, 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed. Results We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS Conclusions Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning. PMID:23801904

Initial in vivo PET imaging of 5-HT1A receptors with 3-[18F]mefway

PubMed Central

Wooten, Dustin W; Hillmer, Ansel T; Murali, Dhanabalan; Barnhart, Todd E; Thio, Joanne P; Bajwa, Alisha K; Bonab, Ali A; Normandin, Marc D; Schneider, Mary L; Mukherjee, Jogeshwar; Christian, Bradley T

2014-01-01

4-trans-[18F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[18F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[18F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[18F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[18F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[18F]mefway to 4-trans-[18F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[18F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[18F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[18F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[18F]mefway suggests the lower BPND of 3-[18F]mefway is due to a lower affinity. The lower affinity of 3-[18F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained. PMID:25143866

Comparison of lesion detection and quantitation of tracer uptake between PET from a simultaneously acquiring whole-body PET/MR hybrid scanner and PET from PET/CT.

PubMed

Wiesmüller, Marco; Quick, Harald H; Navalpakkam, Bharath; Lell, Michael M; Uder, Michael; Ritt, Philipp; Schmidt, Daniela; Beck, Michael; Kuwert, Torsten; von Gall, Carl C

2013-01-01

PET/MR hybrid scanners have recently been introduced, but not yet validated. The aim of this study was to compare the PET components of a PET/CT hybrid system and of a simultaneous whole-body PET/MR hybrid system with regard to reproducibility of lesion detection and quantitation of tracer uptake. A total of 46 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 88 min later a second scan using a hybrid PET/MR system. The radioactive tracers used were (18)F-deoxyglucose (FDG), (18)F-ethylcholine (FEC) and (68)Ga-DOTATATE (Ga-DOTATATE). The PET images from PET/CT (PET(CT)) and from PET/MR (PET(MR)) were analysed for tracer-positive lesions. Regional tracer uptake in these foci was quantified using volumes of interest, and maximal and average standardized uptake values (SUV(max) and SUV(avg), respectively) were calculated. Of the 46 patients, 43 were eligible for comparison and statistical analysis. All lesions except one identified by PET(CT) were identified by PET(MR) (99.2 %). In 38 patients (88.4 %), the same number of foci were identified by PET(CT) and by PET(MR). In four patients, more lesions were identified by PET(MR) than by PET(CT), in one patient PET(CT) revealed an additional focus compared to PET(MR). The mean SUV(max) and SUV(avg) of all lesions determined by PET(MR) were by 21 % and 11 % lower, respectively, than the values determined by PET(CT) (p < 0.05), and a strong correlation between these variables was identified (Spearman rho 0.835; p < 0.01). PET/MR showed equivalent performance in terms of qualitative lesion detection to PET/CT. The differences demonstrated in quantitation of tracer uptake between PET(CT) and PET(MR) were minor, but statistically significant. Nevertheless, a more detailed study of the quantitative accuracy of PET(MR) and the factors governing it is needed to ultimately assess its accuracy in measuring tissue tracer concentrations.

Radiosynthesis and initial characterization of a PDE10A specific PET tracer [18F]AMG 580 in non-human primates.

PubMed

Hwang, Dah-Ren; Hu, Essa; Allen, Jennifer R; Davis, Carl; Treanor, James; Miller, Silke; Chen, Hang; Shi, Bingzhi; Narayanan, Tanjorie K; Barret, Olivier; Alagille, David; Yu, Zhigang; Slifstein, Mark

2015-08-01

Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important second messengers for neurotransmission. Inhibition of PDE10A has been identified as a potential target for treatment of various neuropsychiatric disorders. To assist drug development, we have identified a selective PDE10A positron emission tomography (PET) tracer, AMG 580. We describe here the radiosynthesis of [(18)F]AMG 580 and in vitro and in vivo characterization results. The potency and selectivity were determined by in vitro assay using [(3)H]AMG 580 and baboon brain tissues. [(18)F]AMG 580 was prepared by a 1-step [(18)F]fluorination procedure. Dynamic brain PET scans were performed in non-human primates. Regions-of-interest were defined on individuals' MRIs and transferred to the co-registered PET images. Data were analyzed using two tissue compartment analysis (2TC), Logan graphical (Logan) analysis with metabolite-corrected input function and the simplified reference tissue model (SRTM) method. A PDE10A inhibitor and unlabeled AMG 580 were used to demonstrate the PDE10A specificity. KD was estimated by Scatchard analysis of high and low affinity PET scans. AMG 580 has an in vitro KD of 71.9 pM. Autoradiography showed specific uptake in striatum. Mean activity of 121 ± 18 MBq was used in PET studies. In Rhesus, the baseline BPND for putamen and caudate was 3.38 and 2.34, respectively, via 2TC, and 3.16, 2.34 via Logan, and 2.92, and 2.01 via SRTM. A dose dependent decrease of BPND was observed by the pre-treatment with a PDE10A inhibitor. In baboons, 0.24 mg/kg dose of AMG 580 resulted in about 70% decrease of BPND. The in vivo KD of [(18)F]AMG 580 was estimated to be around 0.44 nM in baboons. [(18)F]AMG 580 is a selective and potent PDE10A PET tracer with excellent specific striatal binding in non-human primates. It warrants further evaluation in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

TH-EF-207A-02: Imaging Pancreatic Î{sup 2}-Cell Function with 51/52Mn-PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graves, S; Hernandez, R; England, C

Purpose: To image β-cells noninvasively using radio-manganese PET and to develop efficient small cyclotron production of {sup 51}Mn (t1/2=46m, β{sup +}=97%) and {sup 52}Mn (t1/2=5.6d, β{sup +}=29%). Methods: {sup 51}Mn and {sup 52}Mn were produced by 16 MeV proton irradiation (GE PETtrace) of electrodeposited {sup 54}Fe on silver and Cr metal pressed into a silver disc, respectively. {sup 51}Mn was radiochemically isolated from target material by anion exchange chromatography and {sup 52}Mn was isolated by ethanolic anion exchange trap-and-release. A final injectable product of {sup 51}Mn{sup 2+} or {sup 52}Mn{sup 2+} was obtained in 0.01M pH 6.0 NaOAc. To assessmore » pancreatic uptake, fasted ICR mice were administered and intravenous bolus or infusion of {sup 52}Mn{sup 2+}. Additionally, to demonstrate the correlation between β-cell function and {sup 52}Mn{sup 2+} pancreatic uptake, prior to tracer administration groups of ICR mice were administered glibenclamide (5mg/kg) and diazoxide (20 mg/kg) as an insulin release stimulator and blocker, respectively. To validate PET ROI quantification, ex vivo biodistribtution studies were conducted on each subject after the final imaging time-point. Results: Dynamic PET data using a left atrium ROI revealed that {sup 52}Mn{sup 2+} cleared from the blood with a 10 second half-life. Significant uptake was seen in the pancreas (approximately 20% ID/g, SUVmean= 5.5), liver, kidneys, intestine, heart, and thyroid. Pancreatic uptake was found to be highly sensitive to volatile anesthesia administration (p=0.0002), insulin release stimulation by glibenclamide (p=0.017), and by insulin release inhibition by diazoxide (p=0.046). Excellent agreement was found between in vivo PET ROI quantification and ex vivo biodistribution measurements. Conclusion: This work demonstrates the feasibility of using radiomanganese-PET for measuring functional β-cell mass in vivo. The decay characteristics and dosimetric properties of {sup 51}Mn are well suited for clinical PET, which will allow for rapid translation and application.« less

Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nyflot, Matthew J., E-mail: nyflot@uw.edu; Kruser, Tim J.; Traynor, Anne M.

2015-04-01

Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curativemore » intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable changes in tumor proliferation, hypoxia, and perfusion after bevacizumab monotherapy and during chemoradiation therapy. These findings suggest opportunities to preview the clinical outcomes for individual patients and thereby design personalized therapy approaches in future trials.« less

[¹⁸F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.

PubMed

Marti-Climent, J M; Dominguez-Prado, I; Garcia-Velloso, M J; Boni, V; Peñuelas, I; Toledo, I; Richter, J A

2014-01-01

To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index. Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively). [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Does pet arrival trigger prosocial behaviors in individuals with autism?

PubMed

Grandgeorge, Marine; Tordjman, Sylvie; Lazartigues, Alain; Lemonnier, Eric; Deleau, Michel; Hausberger, Martine

2012-01-01

Alteration of social interactions especially prosocial behaviors--an important aspect of development--is one of the characteristics of autistic disorders. Numerous strategies or therapies are used to improve communication skills or at least to reduce social impairments. Animal-assisted therapies are used widely but their relevant benefits have never been scientifically evaluated. In the present study, we evaluated the association between the presence or the arrival of pets in families with an individual with autism and the changes in his or her prosocial behaviors. Of 260 individuals with autism--on the basis of presence or absence of pets--two groups of 12 individuals and two groups of 8 individuals were assigned to: study 1 (pet arrival after age of 5 versus no pet) and study 2 (pet versus no pet), respectively. Evaluation of social impairment was assessed at two time periods using the 36-items ADI-R algorithm and a parental questionnaire about their child-pet relationships. The results showed that 2 of the 36 items changed positively between the age of 4 to 5 (t(0)) and time of assessment (t(1)) in the pet arrival group (study 1): "offering to share" and "offering comfort". Interestingly, these two items reflect prosocial behaviors. There seemed to be no significant changes in any item for the three other groups. The interactions between individuals with autism and their pets were more--qualitatively and quantitatively--reported in the situation of pet arrival than pet presence since birth. These findings open further lines of research on the impact of pet's presence or arrival in families with an individual with autism. Given the potential ability of individuals with autism to develop prosocial behaviors, related studies are needed to better understand the mechanisms involved in the development of such child-pet relationship.

Dosimetric verification for primary focal hypermetabolism of nasopharyngeal carcinoma patients treated with dynamic intensity-modulated radiation therapy.

PubMed

Xin, Yong; Wang, Jia-Yang; Li, Liang; Tang, Tian-You; Liu, Gui-Hong; Wang, Jian-She; Xu, Yu-Mei; Chen, Yong; Zhang, Long-Zhen

2012-01-01

To make sure the feasibility with (18F)FDG PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and (18F)FDG PET/CT). The dose distributions of the various regional were realized by SMART. The absolute mean errors of interest area were 2.39%±0.66 using 0.6 cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

Assessment of blood flow with 68Ga-DOTA PET in experimental inflammation: a validation study using 15O-water

PubMed Central

Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

2014-01-01

Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N‘,N‘‘,N‘‘‘-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog (68Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 15O) and 30-min 68Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 15O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of 68Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the 68Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 15O-based blood flow and 68Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that 68Ga-DOTA PET imaging is useful for the quantification of increased blood flow induced by inflammation. PMID:25250206

Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: a validation study using (15)O-water.

PubMed

Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

2014-01-01

Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog ((68)Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 (15)O) and 30-min (68)Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 (15)O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of (68)Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the (68)Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 (15)O-based blood flow and (68)Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that (68)Ga-DOTA PET imaging is useful for the quantification of increased blood flow induced by inflammation.

Accurate 3D reconstruction by a new PDS-OSEM algorithm for HRRT

NASA Astrophysics Data System (ADS)

Chen, Tai-Been; Horng-Shing Lu, Henry; Kim, Hang-Keun; Son, Young-Don; Cho, Zang-Hee

2014-03-01

State-of-the-art high resolution research tomography (HRRT) provides high resolution PET images with full 3D human brain scanning. But, a short time frame in dynamic study causes many problems related to the low counts in the acquired data. The PDS-OSEM algorithm was proposed to reconstruct the HRRT image with a high signal-to-noise ratio that provides accurate information for dynamic data. The new algorithm was evaluated by simulated image, empirical phantoms, and real human brain data. Meanwhile, the time activity curve was adopted to validate a reconstructed performance of dynamic data between PDS-OSEM and OP-OSEM algorithms. According to simulated and empirical studies, the PDS-OSEM algorithm reconstructs images with higher quality, higher accuracy, less noise, and less average sum of square error than those of OP-OSEM. The presented algorithm is useful to provide quality images under the condition of low count rates in dynamic studies with a short scan time.

Human (13)N-ammonia PET studies: the importance of measuring (13)N-ammonia metabolites in blood.

PubMed

Keiding, Susanne; Sørensen, Michael; Munk, Ole Lajord; Bender, Dirk

2010-03-01

Dynamic (13)N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood (13)N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of (13)N-content in blood into (13)N-ammonia, (13)N-urea, (13)N-glutamine and (13)N-glutamate. Due to a radioactive half-life for (13)N of 10 min, the procedure is not suitable for blood samples taken beyond 5-7 min after tracer injection. By modifying Rosenspire's method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate (13)N-ammonia injections with a 60-min interval. Blood data from a (13)N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of (13)N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of (13)N-ammonia to (13)N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total (13)N-concentration in blood as input function, whereas assessment of metabolic processes requires (13)N-ammonia measurements.

Can Imaging Parameters Provide Information Regarding Histopathology in Head and Neck Squamous Cell Carcinoma? A Meta-Analysis.

PubMed

Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

2018-04-01

Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation coefficients between different imaging parameters and histopathological findings were acquired for the analysis. Associations between 18 F-FDG positron emission tomography (PET) and KI 67 were reported in 8 studies (236 patients). The pooled correlation coefficient was 0.20 (95% CI = [-0.04; 0.44]). Furthermore, in 4 studies (64 patients), associations between 18 F-fluorothymidine PET and KI 67 were analyzed. The pooled correlation coefficient between SUV max and KI 67 was 0.28 (95% CI = [-0.06; 0.94]). In 2 studies (23 patients), relationships between KI 67 and dynamic contrast-enhanced magnetic resonance imaging were reported. The pooled correlation coefficient between K trans and KI 67 was -0.68 (95% CI = [-0.91; -0.44]). Two studies (31 patients) investigated correlation between apparent diffusion coefficient (ADC) and KI 67. The pooled correlation coefficient was -0.61 (95% CI = [-0.84; -0.38]). In 2 studies (117 patients), relationships between 18 F-FDG PET and p53 were analyzed. The pooled correlation coefficient was 0.0 (95% CI = [-0.87; 0.88]). There were 3 studies (48 patients) that investigated associations between ADC and tumor cell count in HNSCC. The pooled correlation coefficient was -0.53 (95% CI = [-0.74; -0.32]). Associations between 18 F-FDG PET and HIF-1α were investigated in 3 studies (72 patients). The pooled correlation coefficient was 0.44 (95% CI = [-0.20; 1.08]). ADC may predict cell count and proliferation activity, and SUV max may predict expression of HIF-1α in HNSCC. SUV max cannot be used as surrogate marker for expression of KI 67 and p53. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of the partial volume correction method on 18F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM

PubMed Central

Bowen, Spencer L.; Byars, Larry G.; Michel, Christian J.; Chonde, Daniel B.; Catana, Ciprian

2014-01-01

Kinetic parameters estimated from dynamic 18F-fluorodeoxyglucose PET acquisitions have been used frequently to assess brain function in humans. Neglecting partial volume correction (PVC) for a dynamic series has been shown to produce significant bias in model estimates. Accurate PVC requires a space-variant model describing the reconstructed image spatial point spread function (PSF) that accounts for resolution limitations, including non-uniformities across the field of view due to the parallax effect. For OSEM, image resolution convergence is local and influenced significantly by the number of iterations, the count density, and background-to-target ratio. As both count density and background-to-target values for a brain structure can change during a dynamic scan, the local image resolution may also concurrently vary. When PVC is applied post-reconstruction the kinetic parameter estimates may be biased when neglecting the frame-dependent resolution. We explored the influence of the PVC method and implementation on kinetic parameters estimated by fitting 18F-fluorodeoxyglucose dynamic data acquired on a dedicated brain PET scanner and reconstructed with and without PSF modelling in the OSEM algorithm. The performance of several PVC algorithms was quantified with a phantom experiment, an anthropomorphic Monte Carlo simulation, and a patient scan. Using the last frame reconstructed image only for regional spread function (RSF) generation, as opposed to computing RSFs for each frame independently, and applying perturbation GTM PVC with PSF based OSEM produced the lowest magnitude bias kinetic parameter estimates in most instances, although at the cost of increased noise compared to the PVC methods utilizing conventional OSEM. Use of the last frame RSFs for PVC with no PSF modelling in the OSEM algorithm produced the lowest bias in CMRGlc estimates, although by less than 5% in most cases compared to the other PVC methods. The results indicate that the PVC implementation and choice of PSF modelling in the reconstruction can significantly impact model parameters. PMID:24052021

Combined striatal binding and cerebral influx analysis of dynamic 11C-raclopride PET improves early differentiation between multiple-system atrophy and Parkinson disease.

PubMed

Van Laere, Koen; Clerinx, Kristien; D'Hondt, Eduard; de Groot, Tjibbe; Vandenberghe, Wim

2010-04-01

Striatal dopamine D(2) receptor (D2R) PET has been proposed to differentiate between Parkinson disease (PD) and multiple-system atrophy with predominant parkinsonism (MSA-P). However, considerable overlap in striatal D(2) binding may exist between PD and MSA-P. It has been shown that imaging of neuronal activity, as determined by metabolism or perfusion, can also help distinguish PD from MSA-P. We investigated whether the differential diagnostic value of (11)C-raclopride PET could be improved by dynamic scan analysis combining D2R binding and regional tracer influx. (11)C-raclopride PET was performed in 9 MSA-P patients (mean age +/- SD, 56.2 +/- 10.2 y; disease duration, 2.9 +/- 0.8 y; median Hoehn-Yahr score, 3), 10 PD patients (mean age +/- SD, 65.7 +/- 8.1 y; disease duration, 3.3 +/- 1.5 y; median Hoehn-Yahr score, 1.5), and 10 healthy controls (mean age +/- SD, 61.6 +/- 6.5 y). Diagnosis was obtained after prolonged follow-up (MSA-P, 5.5 +/- 2.0 y; PD, 6.0 +/- 2.3 y) using validated clinical criteria. Spatially normalized parametric images of binding potential (BP) and local influx ratio (R(1) = K(1)/K'(1)) of (11)C-raclopride were obtained using a voxelwise reference tissue model with occipital cortex as reference region. Stepwise forward discriminant analysis with cross-validation, with and without the inclusion of regional R(1) values, was performed using a predefined volume-of-interest template. Using conventional BP values, we correctly classified 65.5% (all values given with cross-validation) of 29 cases only. The combination of BP and R(1) information increased discrimination accuracy to 79.3%. When healthy controls were not included and patients only were considered, BP information alone discriminated PD and MSA-P in 84.2% of cases, but the combination with R(1) data increased accuracy to 100%. Discriminant analysis using combined striatal D2R BP and cerebral influx ratio information of a single dynamic (11)C-raclopride PET scan distinguishes MSA-P and PD patients with high accuracy and is superior to conventional methods of striatal D2R binding analysis.

Quantitative Assessment of Heterogeneity in Tumor Metabolism Using FDG-PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vriens, Dennis, E-mail: d.vriens@nucmed.umcn.nl; Disselhorst, Jonathan A.; Oyen, Wim J.G.

2012-04-01

Purpose: [{sup 18}F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) images are usually quantitatively analyzed in 'whole-tumor' volumes of interest. Also parameters determined with dynamic PET acquisitions, such as the Patlak glucose metabolic rate (MR{sub glc}) and pharmacokinetic rate constants of two-tissue compartment modeling, are most often derived per lesion. We propose segmentation of tumors to determine tumor heterogeneity, potentially useful for dose-painting in radiotherapy and elucidating mechanisms of FDG uptake. Methods and Materials: In 41 patients with 104 lesions, dynamic FDG-PET was performed. On MR{sub glc} images, tumors were segmented in quartiles of background subtracted maximum MR{sub glc} (0%-25%, 25%-50%, 50%-75%, and 75%-100%).more » Pharmacokinetic analysis was performed using an irreversible two-tissue compartment model in the three segments with highest MR{sub glc} to determine the rate constants of FDG metabolism. Results: From the highest to the lowest quartile, significant decreases of uptake (K{sub 1}), washout (k{sub 2}), and phosphorylation (k{sub 3}) rate constants were seen with significant increases in tissue blood volume fraction (V{sub b}). Conclusions: Tumor regions with highest MR{sub glc} are characterized by high cellular uptake and phosphorylation rate constants with relatively low blood volume fractions. In regions with less metabolic activity, the blood volume fraction increases and cellular uptake, washout, and phosphorylation rate constants decrease. These results support the hypothesis that regional tumor glucose phosphorylation rate is not dependent on the transport of nutrients (i.e., FDG) to the tumor.« less

Modeling and predicting tumor response in radioligand therapy.

PubMed

Kletting, Peter; Thieme, Anne; Eberhardt, Nina; Rinscheid, Andreas; D'Alessandria, Calogero; Allmann, Jakob; Wester, Hans-Jürgen; Tauber, Robert; Beer, Ambros J; Glatting, Gerhard; Eiber, Matthias

2018-05-10

The aim of this work was to develop a theranostic method that allows predicting PSMA-positive tumor volume after radioligand therapy (RLT) based on a pre-therapeutic PET/CT measurement and physiologically based pharmacokinetic/dynamic (PBPK/PD) modeling at the example of RLT using 177 Lu-labeled PSMA for imaging and therapy (PSMA I&T). Methods: A recently developed PBPK model for 177 Lu PSMA I&T RLT was extended to account for tumor (exponential) growth and reduction due to irradiation (linear quadratic model). Data of 13 patients with metastatic castration-resistant prostate cancer (mCRPC) were retrospectively analyzed. Pharmacokinetic/dynamic parameters were simultaneously fitted in a Bayesian framework to PET/CT activity concentrations, planar scintigraphy data and tumor volumes prior and post (6 weeks) therapy. The method was validated using the leave-one-out Jackknife method. The tumor volume post therapy was predicted based on pre-therapy PET/CT imaging and PBPK/PD modeling. Results: The relative deviation of the predicted and measured tumor volume for PSMA-positive tumor cells (6 weeks post therapy) was 1±40% excluding one patient (PSA negative) from the population. The radiosensitivity for the PSA positive patients was determined to be 0.0172±0.0084 Gy-1. Conclusion: The proposed method is the first attempt to solely use PET/CT and modeling methods to predict the PSMA-positive tumor volume after radioligand therapy. Internal validation shows that this is feasible with an acceptable accuracy. Improvement of the method and external validation of the model is ongoing. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Molecular dynamics simulation of three plastic additives' diffusion in polyethylene terephthalate.

PubMed

Li, Bo; Wang, Zhi-Wei; Lin, Qin-Bao; Hu, Chang-Ying

2017-06-01

Accurate diffusion coefficient data of additives in a polymer are of paramount importance for estimating the migration of the additives over time. This paper shows how this diffusion coefficient can be estimated for three plastic additives [2-(2'-hydroxy-5'-methylphenyl) (UV-P), 2,6-di-tert-butyl-4-methylphenol (BHT) and di-(2-ethylhexyl) phthalate (DEHP)] in polyethylene terephthalate (PET) using the molecular dynamics (MD) simulation method. MD simulations were performed at temperatures of 293-433 K. The diffusion coefficient was calculated through the Einstein relationship connecting the data of mean-square displacement at different times. Comparison of the diffusion coefficients simulated by the MD simulation technique, predicted by the Piringer model and experiments, showed that, except for a few samples, the MD-simulated values were in agreement with the experimental values within one order of magnitude. Furthermore, the diffusion process for additives is discussed in detail, and four factors - the interaction energy between additive molecules and PET, fractional free volume, molecular shape and size, and self-diffusion of the polymer - are proposed to illustrate the microscopic diffusion mechanism. The movement trajectories of additives in PET cell models suggested that the additive molecules oscillate slowly rather than hopping for a long time. Occasionally, when a sufficiently large hole was created adjacently, the molecule could undergo spatial motion by jumping into the free-volume hole and consequently start a continuous oscillation and hop. The results indicate that MD simulation is a useful approach for predicting the microstructure and diffusion coefficient of plastic additives, and help to estimate the migration level of additives from PET packaging.

Human biodistribution and radiation dosimetry of 82Rb.

PubMed

Senthamizhchelvan, Srinivasan; Bravo, Paco E; Esaias, Caroline; Lodge, Martin A; Merrill, Jennifer; Hobbs, Robert F; Sgouros, George; Bengel, Frank M

2010-10-01

Prior estimates of radiation-absorbed doses from (82)Rb, a frequently used PET perfusion tracer, yielded discrepant results. We reevaluated (82)Rb dosimetry using human in vivo biokinetic measurements. Ten healthy volunteers underwent dynamic PET/CT (6 contiguous table positions, each with separate (82)Rb infusion). Source organ volumes of interest were delineated on the CT images and transferred to the PET images to obtain time-integrated activity coefficients. Radiation doses were estimated using OLINDA/EXM 1.0. The highest mean absorbed organ doses (μGy/MBq) were observed for the kidneys (5.81), heart wall (3.86), and lungs (2.96). Mean effective doses were 1.11 ± 0.22 and 1.26 ± 0.20 μSv/MBq using the tissue-weighting factors of the International Commission on Radiological Protection (ICRP), publications 60 and 103, respectively. Our current (82)Rb dosimetry suggests reasonably low radiation exposure. On the basis of this study, a clinical (82)Rb injection of 2 × 1,480 MBq (80 mCi) would result in a mean effective dose of 3.7 mSv using the weighting factors of the ICRP 103-only slightly above the average annual natural background exposure in the United States (3.1 mSv).

Wettability modification of porous PET by atmospheric femtosecond PLD

NASA Astrophysics Data System (ADS)

Assaf, Youssef; Forstmann, Guillaume; Kietzig, Anne-Marie

2018-04-01

In this study, porous structures were created on poly(ethylene terephthalate) (PET) by femtosecond (fs) laser micromachining. While such structures offer a texture that is desirable for several applications, their wettability does not always match the application in question. The aim of this investigation is to tune the wettability of such surfaces by incorporating a controlled amount of nanoparticles into the structure. The machined PET samples were thus used as substrates for fs pulsed laser deposition (PLD) of titanium under ambient conditions. The nanoparticles were deposited as nanochain clusters due to the formation of an oxide layer between individual nanoparticles. The stability of nanoparticle incorporation was tested by placing the samples in an ultrasonic ethanol bath. Results indicated that nanoparticles were still successfully incorporated into the microstructure after sonication. Nanoparticle surface coverage was observed to be controllable through the operating fluence. The dynamic contact angles of the resulting composite surface were observed to decrease with increasing titanium incorporation. Therefore, this work highlights atmospheric fs PLD as a method for wettability modification of high surface area microstructures without undermining their topology. In addition, this technique uses almost the same equipment as the machining process by which the microstructures are initially created, further highlighting its practicality.

Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients.

PubMed

Huang, Yu-Sen; Chen, Jenny Ling-Yu; Hsu, Feng-Ming; Huang, Jei-Yie; Ko, Wei-Chun; Chen, Yi-Chang; Jaw, Fu-Shan; Yen, Ruoh-Fang; Chang, Yeun-Chung

2018-01-01

To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, K trans , k ep , v e , v p , and iAUC 60 . Chest computed tomography (CT) was performed at 3 months after SBRT. SBRT treatment led to tumor changes including significant decreases in the SUV max (-61%, P < 0.001), K trans mean (-72%, P = 0.005), K trans standard deviation (SD; -85%, P = 0.046), k ep mean (-53%, P = 0.014), k ep SD (-63%, P = 0.001), and v p SD (-58%, P = 0.002). The PET SUV max was correlated with the MR k ep mean (P = 0.002) and k ep SD (P < 0.001). The percentage reduction in K trans mean (P < 0.001) and k ep mean (P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUV max > 10 (P = 0.083). In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199. © 2017 International Society for Magnetic Resonance in Medicine.

Feasibility of Rapid Multitracer PET Tumor Imaging

NASA Astrophysics Data System (ADS)

Kadrmas, D. J.; Rust, T. C.

2005-10-01

Positron emission tomography (PET) can characterize different aspects of tumor physiology using various tracers. PET scans are usually performed using only one tracer since there is no explicit signal for distinguishing multiple tracers. We tested the feasibility of rapidly imaging multiple PET tracers using dynamic imaging techniques, where the signals from each tracer are separated based upon differences in tracer half-life, kinetics, and distribution. Time-activity curve populations for FDG, acetate, ATSM, and PTSM were simulated using appropriate compartment models, and noisy dual-tracer curves were computed by shifting and adding the single-tracer curves. Single-tracer components were then estimated from dual-tracer data using two methods: principal component analysis (PCA)-based fits of single-tracer components to multitracer data, and parallel multitracer compartment models estimating single-tracer rate parameters from multitracer time-activity curves. The PCA analysis found that there is information content present for separating multitracer data, and that tracer separability depends upon tracer kinetics, injection order and timing. Multitracer compartment modeling recovered rate parameters for individual tracers with good accuracy but somewhat higher statistical uncertainty than single-tracer results when the injection delay was >10 min. These approaches to processing rapid multitracer PET data may potentially provide a new tool for characterizing multiple aspects of tumor physiology in vivo.

Control of end-tidal PCO2 reduces middle cerebral artery blood velocity variability: implications for physiological neuroimaging.

PubMed

Harris, Ashley D; Ide, Kojiro; Poulin, Marc J; Frayne, Richard

2006-02-15

Breath-by-breath variability of the end-tidal partial pressure of CO2 (Pet(CO2)) has been shown to be associated with cerebral blood flow (CBF) fluctuations. These fluctuations can impact neuroimaging techniques that depend on cerebrovascular blood flow. We hypothesized that controlling Pet(CO2) would reduce CBF variability. Dynamic end-tidal forcing was used to control Pet(CO2) at 1.5 mm Hg above the resting level and to hold the end-tidal partial pressure of oxygen (Pet(O2)) at the resting level. Peak blood velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler ultrasound (TCD) as an index of CBF. Blood velocity parameters and timing features were determined on each waveform and the variance of these parameters was compared between Normal (air breathing) and Forcing (end-tidal gas control) sessions. The variability of all velocity parameters was significantly reduced in the Forcing session. In particular, the variability of the average velocity over the cardiac cycle was decreased by 18.2% (P < 0.001). For the most part, the variability of the timing parameters was unchanged. Thus, we conclude that controlling Pet(CO2) is effective in reducing CBF variability, which would have important implications for physiologic neuroimaging.

Role of New Functional MRI Techniques in the Diagnosis, Staging, and Followup of Gynecological Cancer: Comparison with PET-CT

PubMed Central

Alvarez Moreno, Elena; Jimenez de la Peña, Mar; Cano Alonso, Raquel

2012-01-01

Recent developments in diagnostic imaging techniques have magnified the role and potential of both MRI and PET-CT in female pelvic imaging. This article reviews the techniques and clinical applications of new functional MRI (fMRI) including diffusion-weighted MRI (DWI), dynamic contrast-enhanced (DCE)-MRI, comparing with PET-CT. These new emerging provide not only anatomic but also functional imaging, allowing detection of small volumes of active tumor at diagnosis and early disease relapse, which may not result in detectable morphological changes at conventional imaging. This information is useful in distinguishing between recurrent/residual tumor and post-treatment changes and assessing treatment response, with a clear impact on patient management. Both PET-CT and now fMRI have proved to be very valuable tools for evaluation of gynecologic tumors. Most papers try to compare these techniques, but in our experience both are complementary in management of these patients. Meanwhile PET-CT is superior in diagnosis of ganglionar disease; fMRI presents higher accuracy in local preoperative staging. Both techniques can be used as biomarkers of tumor response and present high accuracy in diagnosis of local recurrence and peritoneal dissemination, with complementary roles depending on histological type, anatomic location and tumoral volume. PMID:22315683

PET image reconstruction: a robust state space approach.

PubMed

Liu, Huafeng; Tian, Yi; Shi, Pengcheng

2005-01-01

Statistical iterative reconstruction algorithms have shown improved image quality over conventional nonstatistical methods in PET by using accurate system response models and measurement noise models. Strictly speaking, however, PET measurements, pre-corrected for accidental coincidences, are neither Poisson nor Gaussian distributed and thus do not meet basic assumptions of these algorithms. In addition, the difficulty in determining the proper system response model also greatly affects the quality of the reconstructed images. In this paper, we explore the usage of state space principles for the estimation of activity map in tomographic PET imaging. The proposed strategy formulates the organ activity distribution through tracer kinetics models, and the photon-counting measurements through observation equations, thus makes it possible to unify the dynamic reconstruction problem and static reconstruction problem into a general framework. Further, it coherently treats the uncertainties of the statistical model of the imaging system and the noisy nature of measurement data. Since H(infinity) filter seeks minimummaximum-error estimates without any assumptions on the system and data noise statistics, it is particular suited for PET image reconstruction where the statistical properties of measurement data and the system model are very complicated. The performance of the proposed framework is evaluated using Shepp-Logan simulated phantom data and real phantom data with favorable results.

Approaches using molecular imaging technology -- use of PET in clinical microdose studies.

PubMed

Wagner, Claudia C; Langer, Oliver

2011-06-19

Positron emission tomography (PET) imaging uses minute amounts of radiolabeled drug tracers and thereby meets the criteria for clinical microdose studies. The advantage of PET, when compared to other analytical methods used in microdose studies, is that the pharmacokinetics (PK) of a drug can be determined in the tissue targeted for drug treatment. PET microdosing already offers interesting applications in clinical oncology and in the development of central nervous system pharmaceuticals and is extending its range of application to many other fields of pharmaceutical medicine. Although requirements for preclinical safety testing for microdose studies have been cut down by regulatory authorities, radiopharmaceuticals increasingly need to be produced under good manufacturing practice (GMP) conditions, which increases the costs of PET microdosing studies. Further challenges in PET microdosing include combining PET with other ultrasensitive analytical methods, such as accelerator mass spectrometry (AMS), to gain plasma PK data of drugs, beyond the short PET examination periods. Finally, conducting clinical PET studies with radiolabeled drugs both at micro- and therapeutic doses is encouraged to answer the question of dose linearity in clinical microdosing. Copyright © 2010 Elsevier B.V. All rights reserved.

Estimation of potential evapotranspiration from extraterrestrial radiation, air temperature and humidity to assess future climate change effects on the vegetation of the Northern Great Plains, USA

USGS Publications Warehouse

King, David A.; Bachelet, Dominique M.; Symstad, Amy J.; Ferschweiler, Ken; Hobbins, Michael

2014-01-01

The potential evapotranspiration (PET) that would occur with unlimited plant access to water is a central driver of simulated plant growth in many ecological models. PET is influenced by solar and longwave radiation, temperature, wind speed, and humidity, but it is often modeled as a function of temperature alone. This approach can cause biases in projections of future climate impacts in part because it confounds the effects of warming due to increased greenhouse gases with that which would be caused by increased radiation from the sun. We developed an algorithm for linking PET to extraterrestrial solar radiation (incoming top-of atmosphere solar radiation), as well as temperature and atmospheric water vapor pressure, and incorporated this algorithm into the dynamic global vegetation model MC1. We tested the new algorithm for the Northern Great Plains, USA, whose remaining grasslands are threatened by continuing woody encroachment. Both the new and the standard temperature-dependent MC1 algorithm adequately simulated current PET, as compared to the more rigorous PenPan model of Rotstayn et al. (2006). However, compared to the standard algorithm, the new algorithm projected a much more gradual increase in PET over the 21st century for three contrasting future climates. This difference led to lower simulated drought effects and hence greater woody encroachment with the new algorithm, illustrating the importance of more rigorous calculations of PET in ecological models dealing with climate change.