[(18)F]-fluorodeoxyglucose positron emission tomography of the cat brain: A feasibility study to investigate osteoarthritis-associated pain.

PubMed

Guillot, Martin; Chartrand, Gabriel; Chav, Ramnada; Rousseau, Jacques; Beaudoin, Jean-François; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lecomte, Roger; de Guise, Jacques A; Troncy, Eric

2015-06-01

The objective of this pilot study was to investigate central nervous system (CNS) changes related to osteoarthritis (OA)-associated chronic pain in cats using [(18)F]-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) imaging. The brains of five normal, healthy (non-OA) cats and seven cats with pain associated with naturally occurring OA were imaged using (18)FDG-PET during a standardized mild anesthesia protocol. The PET images were co-registered over a magnetic resonance image of a cat brain segmented into several regions of interest. Brain metabolism was assessed in these regions using standardized uptake values. The brain metabolism in the secondary somatosensory cortex, thalamus and periaqueductal gray matter was increased significantly (P ≤ 0.005) in OA cats compared with non-OA cats. This study indicates that (18)FDG-PET brain imaging in cats is feasible to investigate CNS changes related to chronic pain. The results also suggest that OA is associated with sustained nociceptive inputs and increased activity of the descending modulatory pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

(64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients.

PubMed

Kurihara, Hiroaki; Hamada, Akinobu; Yoshida, Masayuki; Shimma, Schuichi; Hashimoto, Jun; Yonemori, Kan; Tani, Hitomi; Miyakita, Yasuji; Kanayama, Yousuke; Wada, Yasuhiro; Kodaira, Makoto; Yunokawa, Mayu; Yamamoto, Harukaze; Shimizu, Chikako; Takahashi, Kazuhiro; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro; Tamura, Kenji

2015-01-01

The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. PET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity in metastatic brain tumors was evaluated based on PET images in five patients. Autoradiography, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab. Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in all of five cases, which might indicated that trastuzumab passes through the blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was demonstrated in one patient by autoradiography, immunohistochemistry, and LC-MS/MS. Cu-DOTA-trastuzumab PET could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer. UMIN000004170.

Coregistered whole body magnetic resonance imaging-positron emission tomography (MRI-PET) versus PET-computed tomography plus brain MRI in staging resectable lung cancer: comparisons of clinical effectiveness in a randomized trial.

PubMed

Yi, Chin A; Lee, Kyung Soo; Lee, Ho Yun; Kim, Seonwoo; Kwon, O Jung; Kim, Hojoong; Choi, Joon Young; Kim, Byung-Tae; Hwang, Hye Sun; Shim, Young Mog

2013-05-15

The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging-positron emission tomography (MRI-PET) would increase the number of correctly upstaged patients compared with WB PET-computed tomography (PET-CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC). From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI-PET or WB PET-CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging. Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI-PET group and in 26 of 120 patients (21.7%) in the PET-CT plus brain MRI group (4.2% difference; 95% confidence interval, -6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI-PET group and in 7 of 120 patients (5.8%) in the PET-CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%-20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (-10.7% difference; 95% confidence interval, -20.1% to -1.4%; P = .022). Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI-PET did not appear to help identify significantly more correctly upstaged patients than PET-CT plus brain MRI in patients with NSCLC. Copyright © 2013 American Cancer Society.

Simulation study comparing the helmet-chin PET with a cylindrical PET of the same number of detectors

NASA Astrophysics Data System (ADS)

Ahmed, Abdella M.; Tashima, Hideaki; Yoshida, Eiji; Nishikido, Fumihiko; Yamaya, Taiga

2017-06-01

There is a growing interest in developing brain PET scanners with high sensitivity and high spatial resolution for early diagnosis of neurodegenerative diseases and studies of brain functions. Sensitivity of the PET scanner can be improved by increasing the solid angle. However, conventional PET scanners are designed based on a cylindrical geometry, which may not be the most efficient design for brain imaging in terms of the balance between sensitivity and cost. We proposed a dedicated brain PET scanner based on a hemispheric shape detector and a chin detector (referred to as the helmet-chin PET), which is designed to maximize the solid angle by increasing the number of lines-of-response in the hemisphere. The parallax error, which PET scanners with a large solid angle tend to have, can be suppressed by the use of depth-of-interaction detectors. In this study, we carry out a realistic evaluation of the helmet-chin PET using Monte Carlo simulation based on the 4-layer GSO detector which consists of a 16  ×  16  ×  4 array of crystals with dimensions of 2.8  ×  2.8  ×  7.5 mm3. The purpose of this simulation is to show the gain in imaging performance of the helmet-chin PET compared with the cylindrical PET using the same number of detectors in each configuration. The sensitivity of the helmet-chin PET evaluated with a cylindrical phantom has a significant increase, especially at the top of the (field-of-view) FOV. The peak-NECR of the helmet-chin PET is 1.4 times higher compared to the cylindrical PET. The helmet-chin PET provides relatively low noise images throughout the FOV compared to the cylindrical PET which exhibits enhanced noise at the peripheral regions. The results show the helmet-chin PET can significantly improve the sensitivity and reduce the noise in the reconstructed images.

Design study of dedicated brain PET with polyhedron geometry.

PubMed

Shi, Han; Du, Dong; Xu, JianFeng; Su, Zhihong; Peng, Qiyu

2015-01-01

Despite being the conventional choice, whole body PET cameras with a 76 cm diameter ring are not the optimal means of human brain imaging. In fact, a dedicated brain PET with a better geometrical structure has the potential to achieve a higher sensitivity, a higher signal-to-noise ratio, and a better imaging performance. In this study, a polyhedron geometrical dedicated brain PET (a dodecahedron design) is compared to three other candidates via their geometrical efficiencies by calculating the Solid Angle Fractions (SAF); the three other candidates include a spherical cap design, a cylindrical design, and the conventional whole body PET. The spherical cap and the dodecahedron have an identical SAF that is 58.4% higher than that of a 30 cm diameter cylinder and 5.44 times higher than that of a 76 cm diameter cylinder. The conceptual polygon-shape detectors (including pentagon and hexagon detectors based on the PMT-light-sharing scheme instead of the conventional square-shaped block detector module) are presented for the polyhedron PET design. Monte Carlo simulations are performed in order to validate the detector decoding. The results show that crystals in a pentagon-shape detector can be successfully decoded by Anger Logic. The new detector designs support the polyhedron PET investigation.

The development, past achievements, and future directions of brain PET

PubMed Central

Jones, Terry; Rabiner, Eugenii A

2012-01-01

The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments. PMID:22434067

Radiosynthesis and in Vivo Evaluation of [11C]A1070722, a High Affinity GSK-3 PET Tracer in Primate Brain.

PubMed

Prabhakaran, Jaya; Zanderigo, Francesca; Sai, Kiran Kumar Solingapuram; Rubin-Falcone, Harry; Jorgensen, Matthew J; Kaplan, Jay R; Mintz, Akiva; Mann, J John; Kumar, J S Dileep

2017-08-16

Dysfunction of glycogen synthase kinase 3 (GSK-3) is implicated in the etiology of Alzheimer's disease, Parkinson's disease, diabetes, pain, and cancer. A radiotracer for functional positron emission tomography (PET) imaging could be used to study the kinase in brain disorders and to facilitate the development of small molecule inhibitors of GSK-3 for treatment. At present, there is no target-specific or validated PET tracer available for the in vivo monitoring of GSK-3. We radiolabeled the small molecule inhibitor [ 11 C]1-(7-methoxy- quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)urea ([ 11 C]A1070722) with high affinity to GSK-3 (K i = 0.6 nM) in excellent radiochemical yield. PET imaging experiments in anesthetized vervet/African green monkey exhibited that [ 11 C]A1070722 penetrated the blood-brain barrier (BBB) and accumulated in brain regions, with highest radioactivity binding in frontal cortex followed by parietal cortex and anterior cingulate, and with the lowest bindings found in caudate, putamen, and thalamus, similarly to the known distribution of GSK-3 in human brain. Our studies suggest that [ 11 C]A1070722 can be a potential PET radiotracer for the in vivo quantification of GSK-3 in brain.

[Factor structure of regional CBF and CMRglu values as a tool for the study of default mode of the brain].

PubMed

Kataev, G V; Korotkov, A D; Kireev, M V; Medvedev, S V

2013-01-01

In the present article it was shown that the functional connectivity of brain structures, revealed by factor analysis of resting PET CBF and rCMRglu data, is an adequate tool to study the default mode of the human brain. The identification of neuroanatomic systems of default mode (default mode network) during routine clinical PET investigations is important for further studying the functional organization of the normal brain and its reorganizations in pathological conditions.

Advances in PET Imaging of P-Glycoprotein Function at the Blood-Brain Barrier

PubMed Central

2012-01-01

Efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) restricts substrate compounds from entering the brain and may thus contribute to pharmacoresistance observed in patient groups with refractory epilepsy and HIV. Altered P-gp function has also been implicated in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Positron emission tomography (PET), a molecular imaging modality, has become a promising method to study the role of P-gp at the BBB. The first PET study of P-gp function was conducted in 1998, and during the past 15 years two main categories of P-gp PET tracers have been investigated: tracers that are substrates of P-gp efflux and tracers that are inhibitors of P-gp function. PET, as a noninvasive imaging technique, allows translational research. Examples of this are preclinical investigations of P-gp function before and after administering P-gp modulating drugs, investigations in various animal and disease models, and clinical investigations regarding disease and aging. The objective of the present review is to give an overview of available PET radiotracers for studies of P-gp and to discuss how such studies can be designed. Further, the review summarizes results from PET studies of P-gp function in different central nervous system disorders. PMID:23421673

Partial volume correction using cortical surfaces

NASA Astrophysics Data System (ADS)

Blaasvær, Kamille R.; Haubro, Camilla D.; Eskildsen, Simon F.; Borghammer, Per; Otzen, Daniel; Ostergaard, Lasse R.

2010-03-01

Partial volume effect (PVE) in positron emission tomography (PET) leads to inaccurate estimation of regional metabolic activities among neighbouring tissues with different tracer concentration. This may be one of the main limiting factors in the utilization of PET in clinical practice. Partial volume correction (PVC) methods have been widely studied to address this issue. MRI based PVC methods are well-established.1 Their performance depend on the quality of the co-registration of the MR and PET dataset, on the correctness of the estimated point-spread function (PSF) of the PET scanner and largely on the performance of the segmentation method that divide the brain into brain tissue compartments.1, 2 In the present study a method for PVC is suggested, that utilizes cortical surfaces, to obtain detailed anatomical information. The objectives are to improve the performance of PVC, facilitate a study of the relationship between metabolic activity in the cerebral cortex and cortical thicknesses, and to obtain an improved visualization of PET data. The gray matter metabolic activity after performing PVC was recovered by 99.7 - 99.8 % , in relation to the true activity when testing on simple simulated data with different PSFs and by 97.9 - 100 % when testing on simulated brain PET data at different cortical thicknesses. When studying the relationship between metabolic activities and anatomical structures it was shown on simulated brain PET data, that it is important to correct for PVE in order to get the true relationship.

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.

Evaluating [11C]PBR28 PET for Monitoring Gut and Brain Inflammation in a Rat Model of Chemically Induced Colitis.

PubMed

Kurtys, E; Doorduin, J; Eisel, U L M; Dierckx, R A J O; de Vries, E F J

2017-02-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects an increasing number of patients. High comorbidity is observed between UC and other diseases in which inflammation may be involved, including brain diseases such as cognitive impairment, mental disorders, anxiety, and depression. To investigate the increased occurrence of these brain diseases in patients with UC, non-invasive methods for monitoring peripheral and central inflammation could be applied. Therefore, the goal of this study is to assess the feasibility of monitoring gut and brain inflammation in a rat model of chemically induced colitis by positron emission tomography (PET) with [ 11 C]PBR28, a tracer targeting the translocator protein (TSPO), which is upregulated when microglia and macrophages are activated. Colitis was induced in rats by intra-rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Rats with colitis and healthy control animals were subjected to [ 11 C]PBR28 PET of the abdomen followed by ex vivo biodistribution in order to assess whether inflammation in the gut could be detected. Another group of rats with colitis underwent repetitive [ 11 C]PBR28 PET imaging of the brain to investigate the development of neuroinflammation. Eleven days after TNBS injection, ex vivo biodistribution studies demonstrated increased [ 11 C]PBR28 uptake in the inflamed cecum and colon of rats with colitis as compared to healthy controls, whereas PET imaging did not show any difference between groups at any time. Similarly, repetitive PET imaging of the brain did not reveal any neuroinflammation induced by the TNBS administration in the colon. In contrast, significantly increased [ 11 C]PBR28 uptake in cerebellum could be detected in ex vivo biodistribution studies on day 11. Inflammation in both the gut and the brain of rats with chemically induced colitis was observed by ex vivo biodistribution. However, these effects could not be detected by [ 11 C]PBR28 PET imaging in our colitis model, which is likely due to spill-over effects and insufficient resolution of the PET camera.

Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study.

ERIC Educational Resources Information Center

Muller, R-A.; Behen, M. E.; Rothermel, R. D.; Chugani, D. C.; Muzik, O.; Mangner, T. J.; Chugani, H. T.

1999-01-01

A study used positron emission tomography (PET) to study patterns of brain activation during auditory processing in five high-functioning adults with autism. Results found that participants showed reversed hemispheric dominance during the verbal auditory stimulation and reduced activation of the auditory cortex and cerebellum. (CR)

Nuclear emission-based imaging in the study of brain function

NASA Astrophysics Data System (ADS)

Sossi, Vesna

2016-09-01

Nuclear emission - based imaging has been used in medicine for decades either in the form of Single Photon Emission Computerized Tomography (SPECT) or Positron Emission Tomography (PET). Both techniques are based on radiolabelling molecules of biological interest (radiotracers) with either a gamma (SPECT) or a positron (PET) emitting radionuclide. By detecting radiation from the radiolabels and reconstructing the acquired data it is possible to form an image of the radiotracer distribution in the body and thus obtain information on the biological process that the radiotracer is tagging. While most of the clinical applications of PET are in oncology, where the glucose analogue 18F-flurodeoxyglocose (FDG) is the most commonly used radiotracer, the importance of PET imaging for brain applications is rapidly increasing. Numerous radiotracers exist that can tag different neurotransmitter systems as well as abnormal protein aggregations that are known to underlie several brain diseases: amyloid deposition, a characteristic of Alzheimer's, and, more recently, tau deposition, which is deemed abnormal not only in dementia, but also in Parkinson's syndrome and traumatic brain injury. Imaging has shown that may brain diseases start decades before clinical symptoms, in part explaining the difficulty of developing adequate treatments. This talk will briefly summarize the role of PET imaging in the study of neurodegeneration and discuss the upcoming hybrid PET/MRI imaging instrumentation. NSERC, CIHR, MJFF.

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

Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging

PubMed Central

Pike, Victor W.

2017-01-01

The development of reversibly binding radioligands for imaging brain proteins in vivo, such as enzymes, neurotransmitter transporters, receptors and ion channels, with positron emission tomography (PET) is keenly sought for biomedical studies of neuropsychiatric disorders and for drug discovery and development, but is recognized as being highly challenging at the medicinal chemistry level. This article aims to compile and discuss the main considerations to be taken into account by chemists embarking on programs of radioligand development for PET imaging of brain protein targets. PMID:27087244

Simultaneous 11C-Methionine Positron Emission Tomography/Magnetic Resonance Imaging of Suspected Primary Brain Tumors

PubMed Central

Deuschl, Cornelius; Goericke, Sophia; Grueneisen, Johannes; Sawicki, Lino Morris; Goebel, Juliane; El Hindy, Nicolai; Wrede, Karsten; Binse, Ina; Poeppel, Thorsten; Quick, Harald; Forsting, Michael; Hense, Joerg; Umutlu, Lale; Schlamann, Marc

2016-01-01

Introduction The objective of this study was to assess the diagnostic value of integrated 11C- methionine PET/MRI for suspected primary brain tumors, in comparison to MRI alone. Material and Methods Forty-eight consecutive patients with suspected primary brain tumor were prospectively enrolled for an integrated 11C-methionine PET/MRI. Two neuro-radiologists separately evaluated the MRI alone and the integrated PET/MRI data sets regarding most likely diagnosis and diagnostic confidence on a 5-point scale. Reference standard was histopathology or follow-up imaging. Results Fifty-one suspicious lesions were detected: 16 high-grade glioma and 25 low-grade glioma. Ten non-malignant cerebral lesions were described by the reference standard. MRI alone and integrated PET/MRI each correctly classified 42 of the 51 lesions (82.4%) as neoplastic lesions (WHO grade II, III and IV) or non-malignant lesions (infectious and neoplastic lesions). Diagnostic confidence for all lesions, low-grade astrocytoma and high-grade astrocytoma (3.7 vs. 4.2, 3,1 vs. 3.8, 4.0 vs. 4,7) were significantly (p < 0.05) better with integrated PET/MRI than in MRI alone. Conclusions The present study demonstrates the high potential of integrated 11C-methionine-PET/MRI for the assessment of suspected primary brain tumors. Although integrated methionine PET/MRI does not lead to an improvement of correct diagnoses, diagnostic confidence is significantly improved. PMID:27907162

Recent Developments of 18F-FET PET in Neuro-oncology.

PubMed

Muoio, Barbara; Giovanella, Luca; Treglia, Giorgio

2017-11-23

From the past decade to date several studies about O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) positron emission tomography (PET) in brain tumours have been published in the literature. Objective The aim of this narrative review is to summarize the recent developments and the current role of 18F-FET PET in brain tumours according to recent literature data. Methods Main findings from selected recently published and relevant articles on the role of 18F-FET PET in neuro-oncology were described. Results 18F-FET PET may be useful in the differential diagnosis between brain tumours and non-neoplastic lesions and between low-grade and high-grade gliomas. Integration of 18F-FET PET into surgical planning allows better delineation of the extent of resection beyond margins visible with standard MRI. For biopsy planning, 18F-FET PET is particularly useful in identifying malignant foci within non-contrast-enhancing gliomas. 18F-FET PET may improve the radiation therapy planning in patients with gliomas. This metabolic imaging method may be useful to evaluate treatment response in patients with gliomas and it improves the differential diagnosis between brain tumours recurrence and post-treatment changes. 18F-FET PET may provide useful prognostic information in high-grade gliomas. Conclusions Based on recent literature data 18F-FET PET may provide additional diagnostic information compared to standard MRI in neuro-oncology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Stereotaxic 18F-FDG PET and MRI templates with three-dimensional digital atlas for statistical parametric mapping analysis of tree shrew brain.

PubMed

Huang, Qi; Nie, Binbin; Ma, Chen; Wang, Jing; Zhang, Tianhao; Duan, Shaofeng; Wu, Shang; Liang, Shengxiang; Li, Panlong; Liu, Hua; Sun, Hua; Zhou, Jiangning; Xu, Lin; Shan, Baoci

2018-01-01

Tree shrews are proposed as an alternative animal model to nonhuman primates due to their close affinity to primates. Neuroimaging techniques are widely used to study brain functions and structures of humans and animals. However, tree shrews are rarely applied in neuroimaging field partly due to the lack of available species specific analysis methods. In this study, 10 PET/CT and 10 MRI images of tree shrew brain were used to construct PET and MRI templates; based on histological atlas we reconstructed a three-dimensional digital atlas with 628 structures delineated; then the digital atlas and templates were aligned into a stereotaxic space. Finally, we integrated the digital atlas and templates into a toolbox for tree shrew brain spatial normalization, statistical analysis and results localization. We validated the feasibility of the toolbox by simulated data with lesions in laterodorsal thalamic nucleus (LD). The lesion volumes of simulated PET and MRI images were (12.97±3.91)mm 3 and (7.04±0.84)mm 3 . Statistical results at p<0.005 showed the lesion volumes of PET and MRI were 13.18mm 3 and 8.06mm 3 in LD. To our knowledge, we report the first PET template and digital atlas of tree shrew brain. Compared to the existing MRI templates, our MRI template was aligned into stereotaxic space. And the toolbox is the first software dedicated for tree shrew brain analysis. The templates and digital atlas of tree shrew brain, as well as the toolbox, facilitate the use of tree shrews in neuroimaging field. Copyright © 2017 Elsevier B.V. All rights reserved.

A new brain positron emission tomography scanner with semiconductor detectors for target volume delineation and radiotherapy treatment planning in patients with nasopharyngeal carcinoma.

PubMed

Katoh, Norio; Yasuda, Koichi; Shiga, Tohru; Hasegawa, Masakazu; Onimaru, Rikiya; Shimizu, Shinichi; Bengua, Gerard; Ishikawa, Masayori; Tamaki, Nagara; Shirato, Hiroki

2012-03-15

We compared two treatment planning methods for stereotactic boost for treating nasopharyngeal carcinoma (NPC): the use of conventional whole-body bismuth germanate (BGO) scintillator positron emission tomography (PET(CONV)WB) versus the new brain (BR) PET system using semiconductor detectors (PET(NEW)BR). Twelve patients with NPC were enrolled in this study. [(18)F]Fluorodeoxyglucose-PET images were acquired using both the PET(NEW)BR and the PET(CONV)WB system on the same day. Computed tomography (CT) and two PET data sets were transferred to a treatment planning system, and the PET(CONV)WB and PET(NEW)BR images were coregistered with the same set of CT images. Window width and level values for all PET images were fixed at 3000 and 300, respectively. The gross tumor volume (GTV) was visually delineated on PET images by using either PET(CONV)WB (GTV(CONV)) images or PET(NEW)BR (GTV(NEW)) images. Assuming a stereotactic radiotherapy boost of 7 ports, the prescribed dose delivered to 95% of the planning target volume (PTV) was set to 2000 cGy in 4 fractions. The average absolute volume (±standard deviation [SD]) of GTV(NEW) was 15.7 ml (±9.9) ml, and that of GTV(CONV) was 34.0 (±20.5) ml. The average GTV(NEW) was significantly smaller than that of GTV(CONV) (p = 0.0006). There was no statistically significant difference between the maximum dose (p = 0.0585) and the mean dose (p = 0.2748) of PTV. The radiotherapy treatment plan based on the new gross tumor volume (PLAN(NEW)) significantly reduced maximum doses to the cerebrum and cerebellum (p = 0.0418) and to brain stem (p = 0.0041). Results of the present study suggest that the new brain PET system using semiconductor detectors can provide more accurate tumor delineation than the conventional whole-body BGO PET system and may be an important tool for functional and molecular radiotherapy treatment planning. Copyright © 2012 Elsevier Inc. All rights reserved.

Fatal mechanical asphyxia induces changes in energy utilization in the rat brain: An (18)F-FDG-PET study.

PubMed

Ma, Suhua; You, Shengzhong; Hao, Li; Zhang, Dongchuan; Quan, Li

2015-07-01

This study was designed to evaluate changes in brain glucose metabolism in rats following ligature strangulation. Thirteen male Wistar rats were used in the present study, divided into control (n=7) and asphyxia groups (n=6, ligature strangulation). Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was used to evaluate brain glucose metabolism. Rats were scanned for PET-CT, and image data co-registered with a T2WI MRI template using SPM8 software. Image J was employed to draw regions of interest (ROIs) from the MRI template and acquire ROI activity information from the PET images. In the asphyxia group vs. controls, (18)F-FDG uptake (FU) was decreased in the substantia nigra (25.26%, p<0.001), rhombencephalon (pons/medulla oblongata, 13.92%, p<0.01), hypothalamus (22.06%, p<0.01), ventral tegmentum (10.12%, p<0.05) and amygdala (12.74%, p<0.05); however, FU was increased in motor (18.21%, p<0.05) and visual cortices (19.2%, p<0.05). The glucose metabolism distribution map in the asphyxiated rat brains were substantially changed versus controls. PET with (18)F-FDG can demonstrate excitement and inhibition of different brain areas even in cases of ligature strangulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dual-modality brain PET-CT image segmentation based on adaptive use of functional and anatomical information.

PubMed

Xia, Yong; Eberl, Stefan; Wen, Lingfeng; Fulham, Michael; Feng, David Dagan

2012-01-01

Dual medical imaging modalities, such as PET-CT, are now a routine component of clinical practice. Medical image segmentation methods, however, have generally only been applied to single modality images. In this paper, we propose the dual-modality image segmentation model to segment brain PET-CT images into gray matter, white matter and cerebrospinal fluid. This model converts PET-CT image segmentation into an optimization process controlled simultaneously by PET and CT voxel values and spatial constraints. It is innovative in the creation and application of the modality discriminatory power (MDP) coefficient as a weighting scheme to adaptively combine the functional (PET) and anatomical (CT) information on a voxel-by-voxel basis. Our approach relies upon allowing the modality with higher discriminatory power to play a more important role in the segmentation process. We compared the proposed approach to three other image segmentation strategies, including PET-only based segmentation, combination of the results of independent PET image segmentation and CT image segmentation, and simultaneous segmentation of joint PET and CT images without an adaptive weighting scheme. Our results in 21 clinical studies showed that our approach provides the most accurate and reliable segmentation for brain PET-CT images. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain.

PubMed

Jung, Jin Ho; Choi, Yong; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun; Oh, Chang Hyun; Park, Hyun-wook; Kim, Kyung Min; Kim, Jong Guk

2015-05-01

The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.

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.

PET Mapping for Brain-Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes.

PubMed

Zhu, Yunqi; Xu, Kedi; Xu, Caiyun; Zhang, Jiacheng; Ji, Jianfeng; Zheng, Xiaoxiang; Zhang, Hong; Tian, Mei

2016-07-01

Brain-computer interface (BCI) technology has great potential for improving the quality of life for neurologic patients. This study aimed to use PET mapping for BCI-based stimulation in a rat model with electrodes implanted in the ventroposterior medial (VPM) nucleus of the thalamus. PET imaging studies were conducted before and after stimulation of the right VPM. Stimulation induced significant orienting performance. (18)F-FDG uptake increased significantly in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II of the ansiform lobule of the cerebellum, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex, but it decreased in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the somatosensory cortex. This study demonstrated that PET mapping after VPM stimulation can identify specific brain regions associated with orienting performance. PET molecular imaging may be an important approach for BCI-based research and its clinical applications. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

PubMed

Madsen, Karine; Hesby, Sara; Poulsen, Ingrid; Fuglsang, Stefan; Graff, Jesper; Larsen, Karen B; Kammersgaard, Lars P; Law, Ian; Siebner, Hartwig R

2017-11-01

Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [ 18 F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [ 18 F]FDG-PET scan and venous blood sampling. Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. Our study demonstrates that the analysis method of the [ 18 F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. We recommend supplementing a static [ 18 F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc. Copyright © 2017 Elsevier B.V. All rights reserved.

The metabolism of the human brain studied with positron emission tomography

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

Greitz, T.; Ingvar, D.H.; Widen, L.

1985-01-01

This volume presents coverage of the use of positron emission tomography (PET) to study the human brain. The contributors assess new developments in high-resolution positron emission tomography, cyclotrons, radiochemistry, and tracer kinetic models, and explore the use of PET in brain energy metabolism, blood flow, and protein synthesis measurements, receptor analysis, and pH determinations, In addition, they discuss the relevance and applications of positron emission tomography from the perspectives of physiology, neurology, and psychiatry.

Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

NASA Astrophysics Data System (ADS)

Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

2007-02-01

Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PET (μPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

PET evaluation of the dopamine system of the human brain

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

Volkow, N.D.; Fowler, J.S.; Gatley, S.

1996-07-01

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors,more » dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.« less

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

PubMed

Vas, Adám; Shchukin, Yevgeni; Karrenbauer, Virginija D; Cselényi, Zsolt; Kostulas, Kosta; Hillert, Jan; Savic, Ivanka; Takano, Akihiro; Halldin, Christer; Gulyás, Balázs

2008-01-15

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

Metabolic Imaging in Parkinson Disease.

PubMed

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

PET and Single-Photon Emission Computed Tomography in Brain Concussion.

PubMed

Raji, Cyrus A; Henderson, Theodore A

2018-02-01

This article offers an overview of the application of PET and single photon emission computed tomography brain imaging to concussion, a type of mild traumatic brain injury and traumatic brain injury, in general. The article reviews the application of these neuronuclear imaging modalities in cross-sectional and longitudinal studies. Additionally, this article frames the current literature with an overview of the basic physics and radiation exposure risks of each modality. Copyright © 2017 Elsevier Inc. All rights reserved.

I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury.

PubMed

Abiko, Kagari; Ikoma, Katsunori; Shiga, Tohru; Katoh, Chietsugu; Hirata, Kenji; Kuge, Yuji; Kobayashi, Kentaro; Tamaki, Nagara

2017-12-01

Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whether IMZ SPECT is as useful as FMZ PET for evaluating the loss of neuronal integrity in TBI patients. The subjects of this study were seven patients who suffered from neurobehavioral disability. They underwent IMZ SPECT and FMZ PET. Nondisplaceable binding potential (BP ND ) was calculated from FMZ PET images. The uptake of IMZ was evaluated on the basis of lesion-to-pons ratio (LPR). The locations of low uptake levels were visually evaluated both in IMZ SPECT and FMZ PET images. We compared FMZ BP ND and (LPR-1) of IMZ SPECT. In the visual assessment, FMZ BP ND decreased in 11 regions. In IMZ SPECT, low uptake levels were observed in eight of the 11 regions. The rate of concordance between FMZ PET and IMZ SPECT was 72.7%. The mean values IMZ (LPR-1) (1.95 ± 1.01) was significantly lower than that of FMZ BP ND (2.95 ± 0.80 mL/mL). There was good correlation between FMZ BP ND and IMZ (LPR-1) (r = 0.80). IMZ SPECT findings were almost the same as FMZ PET findings in TBI patients. The results indicated that IMZ SPECT is useful for evaluating the loss of neuronal integrity. Because IMZ SPECT can be performed in various facilities, IMZ SPECT may become widely adopted for evaluating the loss of neuronal integrity.

Cerebral glucose uptake in patients with chronic mental and cognitive sequelae following a single blunt mild TBI without visible brain lesions.

PubMed

Komura, Akifumi; Kawasaki, Tomohiro; Yamada, Yuichi; Uzuyama, Shiho; Asano, Yoshitaka; Shinoda, Jun

2018-06-19

The aim of this study is to investigate glucose uptake on FDG-PET in patients with chronic mental and cognitive symptoms following a single blunt mild traumatic brain injury (TBI) and without visible brain lesions on CT/MRI. Eighty-nine consecutive patients (mean age 43.8±10.75) who had a single blunt mild TBI from a traffic accident and suffering from chronic mental and cognitive symptoms without visible brain lesions on CT/MRI were enrolled in the study. Patients underwent FDG-PET imaging, and the mean interval between the TBI and FDG-PET was 50.0 months. The Wechsler Adult Intelligence Scale version III testing was performed within one month of the FDG-PET. A control group consisting of 93 healthy adult volunteers (mean age 42.2±14.3 years) also underwent FDG-PET. The glucose uptake pattern from FDG-PET in the patient group was compared to that from normal controls using statistical parametric mapping. Glucose uptake was significantly decreased in the bilateral prefrontal area and significantly increased around the limbic system in the patient group compared to normal controls. This topographical pattern of glucose uptake is different from that reported previously in patients with diffuse axonal injury (DAI), but may be similar to that seen in patients with major depression disorder. These results suggest that the pathological mechanism causing chronic mental and cognitive symptoms in patients with a single blunt mild TBI and without visible brain lesions might be different from that due to primary axonopathy in patients with DAI.

Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

PubMed

Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

2016-06-01

There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

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

Jung, Jin Ho; Choi, Yong, E-mail: ychoi.image@gmail.com; Jung, Jiwoong

2015-05-15

Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. Themore » PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired. Conclusions: Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.« less

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.

CHOLESTEROL-RELATED GENETIC RISK SCORES ARE ASSOCIATED WITH HYPOMETABOLISM IN ALZHEIMER’S-AFFECTED BRAIN REGIONS

PubMed Central

Reiman, Eric M.; Chen, Kewei; Caselli, Richard J.; Alexander, Gene E.; Bandy, Daniel; Adamson, Jennifer L.; Lee, Wendy; Cannon, Ashley; Stephan, Elizabeth A.; Stephan, Dietrich A.; Papassotiropoulos, Andreas

2008-01-01

We recently implicated a cluster of nine single nucleotide polymorphisms from seven cholesterol-related genes in the risk of Alzheimer’s disease (AD) in a European cohort, and we proposed calculating an aggregate cholesterol-related genetic score (CREGS) to characterize a person’s risk. In a separate study, we found that apolipoprotein E (APOE) ε4 gene dose, an established AD risk factor, was correlated with fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of hypometabolism in AD-affected brain regions in a cognitively normal American cohort, and we proposed using PET as a presymptomatic endophenotype to help assess putative modifiers of AD risk. Thus, the objective in the present study is to determine whether CREGS is related to PET measurements of hypometabolism in AD-affected brain regions. DNA and PET data from 141 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and non-carriers were analyzed to evaluate the relationship between CREGS and regional PET measurements. Cholesterol-related genetic risk scores were associated with hypometabolism in AD-affected brain regions, even when controlling for the effects of APOE ε4 gene dose. The results support the role of cholesterol-related genes in the predisposition to AD, and support the value of neuroimaging in the presymptomatic assessment of putative modifiers of AD risk. PMID:18280754

Estimation of usefulness of positron emission tomography (PET) in the diagnosis of post-traumatic stress disorders--preliminary report.

PubMed

Wojtłowska-Wiechetek, D; Tworus, R; Dziuk, M; Petrovic, A; Szymańska, S; Zbyszewski, M; Ilnicki, S; Krzesiński, P

2013-01-01

The aim of this study was to evaluate the possibility of using PET both in assessing the susceptibility to stress and in the diagnosis of post-traumatic stress disorders. Mentally and somatically healthy soldiers were subjected to PET-CT head scan examinations before and after virtual reality stimulation with warfare scenarios. Despite stimulation of peripheral nervous system after 10 minutes, VR exposure in any of the examined soldiers simulation did not cause changes in any brain structure that was visualized in PET. PET-CT head scan was also performed in patients with typical symptoms of acute PTSD according to the criteria of DSM IV TR. In those patients no changes in any brain structure was found. Initially it was found that VR exposure techniques like clinically typical acute symptoms of PTSD do not leave changes in CNS, which could be visualized in PET. The preliminary hypothesis was put forward that exposure to stimuli like symptoms of PTSD must remain long enough to induce permanent damage of brain structure.

Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease

PubMed Central

Sehlin, Dag; Fang, Xiaotian T.; Cato, Linda; Antoni, Gunnar; Lannfelt, Lars; Syvänen, Stina

2016-01-01

Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood–brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer's disease. The amyloid β (Aβ) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Aβ pathology clearly visualize Aβ in the brain. The PET signal increases with age and correlates closely with brain Aβ levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging. PMID:26892305

MR/PET quantification tools: Registration, segmentation, classification, and MR-based attenuation correction

PubMed Central

Fei, Baowei; Yang, Xiaofeng; Nye, Jonathon A.; Aarsvold, John N.; Raghunath, Nivedita; Cervo, Morgan; Stark, Rebecca; Meltzer, Carolyn C.; Votaw, John R.

2012-01-01

Purpose: Combined MR/PET is a relatively new, hybrid imaging modality. A human MR/PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR/PET for brain imaging. Methods: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR/PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [11C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. Results: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. Conclusions: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR/PET. PMID:23039679

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

Improved frame-based estimation of head motion in PET brain imaging.

PubMed

Mukherjee, J M; Lindsay, C; Mukherjee, A; Olivier, P; Shao, L; King, M A; Licho, R

2016-05-01

Head motion during PET brain imaging can cause significant degradation of image quality. Several authors have proposed ways to compensate for PET brain motion to restore image quality and improve quantitation. Head restraints can reduce movement but are unreliable; thus the need for alternative strategies such as data-driven motion estimation or external motion tracking. Herein, the authors present a data-driven motion estimation method using a preprocessing technique that allows the usage of very short duration frames, thus reducing the intraframe motion problem commonly observed in the multiple frame acquisition method. The list mode data for PET acquisition is uniformly divided into 5-s frames and images are reconstructed without attenuation correction. Interframe motion is estimated using a 3D multiresolution registration algorithm and subsequently compensated for. For this study, the authors used 8 PET brain studies that used F-18 FDG as the tracer and contained minor or no initial motion. After reconstruction and prior to motion estimation, known motion was introduced to each frame to simulate head motion during a PET acquisition. To investigate the trade-off in motion estimation and compensation with respect to frames of different length, the authors summed 5-s frames accordingly to produce 10 and 60 s frames. Summed images generated from the motion-compensated reconstructed frames were then compared to the original PET image reconstruction without motion compensation. The authors found that our method is able to compensate for both gradual and step-like motions using frame times as short as 5 s with a spatial accuracy of 0.2 mm on average. Complex volunteer motion involving all six degrees of freedom was estimated with lower accuracy (0.3 mm on average) than the other types investigated. Preprocessing of 5-s images was necessary for successful image registration. Since their method utilizes nonattenuation corrected frames, it is not susceptible to motion introduced between CT and PET acquisitions. The authors have shown that they can estimate motion for frames with time intervals as short as 5 s using nonattenuation corrected reconstructed FDG PET brain images. Intraframe motion in 60-s frames causes degradation of accuracy to about 2 mm based on the motion type.

MRI-assisted PET motion correction for neurologic studies in an integrated MR-PET scanner.

PubMed

Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Byars, Larry; Hamm, Michael; Chonde, Daniel B; Michel, Christian J; El Fakhri, Georges; Schmand, Matthias; Sorensen, A Gregory

2011-01-01

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MRI data can be used for motion tracking. In this work, a novel algorithm for data processing and rigid-body motion correction (MC) for the MRI-compatible BrainPET prototype scanner is described, and proof-of-principle phantom and human studies are presented. To account for motion, the PET prompt and random coincidences and sensitivity data for postnormalization were processed in the line-of-response (LOR) space according to the MRI-derived motion estimates. The processing time on the standard BrainPET workstation is approximately 16 s for each motion estimate. After rebinning in the sinogram space, the motion corrected data were summed, and the PET volume was reconstructed using the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed, and motion estimates were obtained using 2 high-temporal-resolution MRI-based motion-tracking techniques. After accounting for the misalignment between the 2 scanners, perfectly coregistered MRI and PET volumes were reproducibly obtained. The MRI output gates inserted into the PET list-mode allow the temporal correlation of the 2 datasets within 0.2 ms. The Hoffman phantom volume reconstructed by processing the PET data in the LOR space was similar to the one obtained by processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the procedure. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 s and 20 ms, respectively. Motion-deblurred PET images, with excellent delineation of specific brain structures, were obtained using these 2 MRI-based estimates. An MRI-based MC algorithm was implemented for an integrated MR-PET scanner. High-temporal-resolution MRI-derived motion estimates (obtained while simultaneously acquiring anatomic or functional MRI data) can be used for PET MC. An MRI-based MC method has the potential to improve PET image quality, increasing its reliability, reproducibility, and quantitative accuracy, and to benefit many neurologic applications.

Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

PubMed

Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

2018-03-12

Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

A computed tomography-based spatial normalization for the analysis of [18F] fluorodeoxyglucose positron emission tomography of the brain.

PubMed

Cho, Hanna; Kim, Jin Su; Choi, Jae Yong; Ryu, Young Hoon; Lyoo, Chul Hyoung

2014-01-01

We developed a new computed tomography (CT)-based spatial normalization method and CT template to demonstrate its usefulness in spatial normalization of positron emission tomography (PET) images with [(18)F] fluorodeoxyglucose (FDG) PET studies in healthy controls. Seventy healthy controls underwent brain CT scan (120 KeV, 180 mAs, and 3 mm of thickness) and [(18)F] FDG PET scans using a PET/CT scanner. T1-weighted magnetic resonance (MR) images were acquired for all subjects. By averaging skull-stripped and spatially-normalized MR and CT images, we created skull-stripped MR and CT templates for spatial normalization. The skull-stripped MR and CT images were spatially normalized to each structural template. PET images were spatially normalized by applying spatial transformation parameters to normalize skull-stripped MR and CT images. A conventional perfusion PET template was used for PET-based spatial normalization. Regional standardized uptake values (SUV) measured by overlaying the template volume of interest (VOI) were compared to those measured with FreeSurfer-generated VOI (FSVOI). All three spatial normalization methods underestimated regional SUV values by 0.3-20% compared to those measured with FSVOI. The CT-based method showed slightly greater underestimation bias. Regional SUV values derived from all three spatial normalization methods were correlated significantly (p < 0.0001) with those measured with FSVOI. CT-based spatial normalization may be an alternative method for structure-based spatial normalization of [(18)F] FDG PET when MR imaging is unavailable. Therefore, it is useful for PET/CT studies with various radiotracers whose uptake is expected to be limited to specific brain regions or highly variable within study population.

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

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.

Specification and estimation of sources of bias affecting neurological studies in PET/MR with an anatomical brain phantom

NASA Astrophysics Data System (ADS)

Teuho, J.; Johansson, J.; Linden, J.; Saunavaara, V.; Tolvanen, T.; Teräs, M.

2014-01-01

Selection of reconstruction parameters has an effect on the image quantification in PET, with an additional contribution from a scanner-specific attenuation correction method. For achieving comparable results in inter- and intra-center comparisons, any existing quantitative differences should be identified and compensated for. In this study, a comparison between PET, PET/CT and PET/MR is performed by using an anatomical brain phantom, to identify and measure the amount of bias caused due to differences in reconstruction and attenuation correction methods especially in PET/MR. Differences were estimated by using visual, qualitative and quantitative analysis. The qualitative analysis consisted of a line profile analysis for measuring the reproduction of anatomical structures and the contribution of the amount of iterations to image contrast. The quantitative analysis consisted of measurement and comparison of 10 anatomical VOIs, where the HRRT was considered as the reference. All scanners reproduced the main anatomical structures of the phantom adequately, although the image contrast on the PET/MR was inferior when using a default clinical brain protocol. Image contrast was improved by increasing the amount of iterations from 2 to 5 while using 33 subsets. Furthermore, a PET/MR-specific bias was detected, which resulted in underestimation of the activity values in anatomical structures closest to the skull, due to the MR-derived attenuation map that ignores the bone. Thus, further improvements for the PET/MR reconstruction and attenuation correction could be achieved by optimization of RAMLA-specific reconstruction parameters and implementation of bone to the attenuation template.

Longitudinal Changes in Serum Glucose Levels are Associated with Metabolic Changes in Alzheimer's Disease Related Brain Regions.

PubMed

Burns, Christine M; Kaszniak, Alfred W; Chen, Kewei; Lee, Wendy; Bandy, Daniel J; Caselli, Richard J; Reiman, Eric M

2018-01-01

The association between longitudinal changes in serum glucose level and longitudinal changes in [18F] Fluorodeoxyglucose-PET (FDG PET) measurements of Alzheimer's disease (AD) risk are unknown. To investigate whether variation in serum glucose levels across time are associated with changes in FDG PET measurements of cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer's disease (AD). Participants are a subset of a prospective cohort study investigating FDG PET, apolipoprotein E (APOE) ɛ4, and risk for AD which includes data from baseline, interim, and follow up visits over 4.4±1.0-years. An automated brain-mapping algorithm was utilized to characterize and compare associations between longitudinal changes in serum glucose levels and longitudinal changes in rCMRgl. This study included 80 adults aged 61.5±5 years, including 38 carriers and 42 non-carriers of the APOE ɛ4 allele. Longitudinal increases in serum glucose levels were associated with longitudinal CMRgl decline in the vicinity of parietotemporal, precuneus/posterior cingulate, and prefrontal brain regions preferentially affected by AD (p < 0.05, corrected for multiple comparisons). Findings remained significant when controlled for APOE ɛ4 status and baseline and advancing age. Additional studies are needed to clarify and confirm the relationship between longitudinal changes in peripheral glucose and FDG PET measurements of AD risk. Future findings will set the stage on the use of FDG PET in the evaluation of possible interventions that target risk factors for the development of AD.

Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

PubMed

Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

2018-02-01

Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

Histone Deacetylase Inhibitor MS-275 Exhibits Poor Brain Penetration: Pharmacokinetic Studies of [11C]MS-275 using Positron Emission Tomography

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

Hooker, J.M.; Hooker, J.M.; Kim, S.W.

2009-10-01

MS-275 (entinostat) is a histone deacetylase (HDAC) inhibitor currently in clinical trials for the treatment of several types of cancer. Recent reports have noted that MS-275 can cross the blood-brain barrier (BBB) and cause region-specific changes in rodent brain histone acetylation. To characterize the pharmacokinetics and distribution of MS-275 in the brain using positron emission tomography (PET), we labeled the carbamate carbon of MS-275 with carbon-11. Using PET, we determined that [{sup 11}C]MS-275 has low uptake in brain tissue when administered intravenously to nonhuman primates. In rodent studies, we observed that pharmacokinetics and brain accumulation of [{sup 11}C]MS-275 were notmore » changed by the coadministration of large doses of unlabeled MS-275. These results, which both highlight the poor brain penetration of MS-275, clearly suggest its limitation as a therapeutic agent for the central nervous system (CNS). Moreover, our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for HDAC inhibitors. These data are important not only for the development of new compounds for peripheral cancer treatment (where CNS exclusion is often advantageous) but also for the treatment of neurological disorders (where CNS penetration is critical).« less

Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

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

Kronfeld, Andrea; Müller-Forell, Wibke; Buchholz, Hans-Georg

Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawleymore » rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL templates together with nonlinear registration algorithms allows for accurate spatial normalization of combined MRI/PET or PET-only studies.« less

Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI.

PubMed

Olcott, Peter; Kim, Ealgoo; Hong, Keyjo; Lee, Brian J; Grant, Alexander M; Chang, Chen-Ming; Glover, Gary; Levin, Craig S

2015-05-07

The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI

NASA Astrophysics Data System (ADS)

Olcott, Peter; Kim, Ealgoo; Hong, Keyjo; Lee, Brian J.; Grant, Alexander M.; Chang, Chen-Ming; Glover, Gary; Levin, Craig S.

2015-05-01

The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

Efficiency gains in tracer identification for nuclear imaging: can in vivo LC-MS/MS evaluation of small molecules screen for successful PET tracers?

PubMed

Joshi, Elizabeth M; Need, Anne; Schaus, John; Chen, Zhaogen; Benesh, Dana; Mitch, Charles; Morton, Stuart; Raub, Thomas J; Phebus, Lee; Barth, Vanessa

2014-12-17

Positron emission tomography (PET) imaging has become a useful noninvasive technique to explore molecular biology within living systems; however, the utility of this method is limited by the availability of suitable radiotracers to probe specific targets and disease biology. Methods to identify potential areas of improvement in the ability to predict small molecule performance as tracers prior to radiolabeling would speed the discovery of novel tracers. In this retrospective analysis, we characterized the brain penetration or peak SUV (standardized uptake value), binding potential (BP), and brain exposure kinetics across a series of known, nonradiolabeled PET ligands using in vivo LC-MS/MS (liquid chromatography coupled to mass spectrometry) and correlated these parameters with the reported PET ligand performance in nonhuman primates and humans available in the literature. The PET tracers studied included those reported to label G protein-coupled receptors (GPCRs), intracellular enzymes, and transporters. Additionally, data for each tracer was obtained from a mouse brain uptake assay (MBUA), previously published, where blood-brain barrier (BBB) penetration and clearance parameters were assessed and compared against similar data collected on a broad compound set of central nervous system (CNS) therapeutic compounds. The BP and SUV identified via nonradiolabeled LC-MS/MS, while different from the published values observed in the literature PET tracer data, allowed for an identification of initial criteria values we sought to facilitate increased potential for success from our early discovery screening paradigm. Our analysis showed that successful, as well as novel, clinical PET tracers exhibited BP of greater than 1.5 and peak SUVs greater than approximately 150% at 5 min post dose in rodents. The brain kinetics appeared similar between both techniques despite differences in tracer dose, suggesting linearity across these dose ranges. The assessment of tracers in a CNS exposure model, the mouse brain uptake assessment (MBUA), showed that those compound with initial brain-to-plasma ratios >2 and unbound fraction in brain homogenate >0.01 were more likely to be clinically successful PET ligands. Taken together, early incorporation of a LC/MS/MS cold tracer discovery assay and a parallel MBUA can be an useful screening paradigm to prioritize and rank order potential novel PET radioligands during early tracer discovery efforts. Compounds considered for continued in vivo PET assessments can be identified quickly by leveraging in vitro affinity and selectivity measures, coupled with data from a MBUA, primarily the 5 min brain-to-plasma ratio and unbound fraction data. Coupled utilization of these data creates a strategy to efficiently screen for the identification of appropriate chemical space to invest in for radiotracer discovery.

18F-NaF PET Demonstrating Unusual Focal Tracer Activity in the Brain.

PubMed

Thenkondar, Anuradha; Jafari, Lida; Sooriash, Robbie; Hajsadeghi, Fereshteh; Berenji, Gholam R; Li, Yuxin

2017-02-01

A 60-year-old man with enlarged prostate, hypertension, and diabetes was referred for F-NaF PET/CT to evaluate possible metastatic lesions. The patient appeared asymptomatic on the day of the study, without any signs indicating stroke. Patient also had no known history of malignancy or cerebrovascular disease. He had mild elevation of the prostate-specific antigen level, and biopsy of his prostate was not performed. Patient had long-standing history of chronic back pain and abdominal pain. The PET bone scan demonstrated a large area of very intense tracer uptake in the brain. A subsequent brain MRI revealed prior stroke in the same area.

Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB.

PubMed

McCann, Una D; Szabo, Zsolt; Seckin, Esen; Rosenblatt, Peter; Mathews, William B; Ravert, Hayden T; Dannals, Robert F; Ricaurte, George A

2005-09-01

(+/-)3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') is a widely used illicit drug that produces toxic effects on brain serotonin axons and axon terminals in animals. The results of clinical studies addressing MDMA's serotonin neurotoxic potential in humans have been inconclusive. In the present study, 23 abstinent MDMA users and 19 non-MDMA controls underwent quantitative positron emission tomography (PET) studies using [11C]McN5652 and [11C]DASB, first- and second-generation serotonin transporter (SERT) ligands previously validated in baboons for detecting MDMA-induced brain serotonin neurotoxicity. Global and regional distribution volumes (DVs) and two additional SERT-binding parameters (DV(spec) and DVR) were compared in the two subject populations using parametric statistical analyses. Data from PET studies revealed excellent correlations between the various binding parameters of [11C]McN5652 and [11C]DASB, both in individual brain regions and individual subjects. Global SERT reductions were found in MDMA users with both PET ligands, using all three of the above-mentioned SERT-binding parameters. Preplanned comparisons in 15 regions of interest demonstrated reductions in selected cortical and subcortical structures. Exploratory correlational analyses suggested that SERT measures recover with time, and that loss of the SERT is directly associated with MDMA use intensity. These quantitative PET data, obtained using validated first- and second-generation SERT PET ligands, provide strong evidence of reduced SERT density in some recreational MDMA users.

PET/MRI for Oncologic Brain Imaging: A Comparison of Standard MR-Based Attenuation Corrections with a Model-Based Approach for the Siemens mMR PET/MR System.

PubMed

Rausch, Ivo; Rischka, Lucas; Ladefoged, Claes N; Furtner, Julia; Fenchel, Matthias; Hahn, Andreas; Lanzenberger, Rupert; Mayerhoefer, Marius E; Traub-Weidinger, Tatjana; Beyer, Thomas

2017-09-01

The aim of this study was to compare attenuation-correction (AC) approaches for PET/MRI in clinical neurooncology. Methods: Forty-nine PET/MRI brain scans were included: brain tumor studies using 18 F-fluoro-ethyl-tyrosine ( 18 F-FET) ( n = 31) and 68 Ga-DOTANOC ( n = 7) and studies of healthy subjects using 18 F-FDG ( n = 11). For each subject, MR-based AC maps (MR-AC) were acquired using the standard DIXON- and ultrashort echo time (UTE)-based approaches. A third MR-AC was calculated using a model-based, postprocessing approach to account for bone attenuation values (BD, noncommercial prototype software by Siemens Healthcare). As a reference, AC maps were derived from patient-specific CT images (CTref). PET data were reconstructed using standard settings after AC with all 4 AC methods. We report changes in diagnosis for all brain tumor patients and the following relative differences values (RDs [%]), with regards to AC-CTref: for 18 F-FET (A)-SUVs as well as volumes of interest (VOIs) defined by a 70% threshold of all segmented lesions and lesion-to-background ratios; for 68 Ga-DOTANOC (B)-SUVs as well as VOIs defined by a 50% threshold for all lesions and the pituitary gland; and for 18 F-FDG (C)-RD of SUVs of the whole brain and 10 anatomic regions segmented on MR images. Results: For brain tumor imaging (A and B), the standard PET-based diagnosis was not affected by any of the 3 MR-AC methods. For A, the average RDs of SUV mean were -10%, -4%, and -3% and of the VOIs 1%, 2%, and 7% for DIXON, UTE, and BD, respectively. Lesion-to-background ratios for all MR-AC methods were similar to that of CTref. For B, average RDs of SUV mean were -11%, -11%, and -3% and of the VOIs 1%, -4%, and -3%, respectively. In the case of 18 F-FDG PET/MRI (C), RDs for the whole brain were -11%, -8%, and -5% for DIXON, UTE, and BD, respectively. Conclusion: The diagnostic reading of PET/MR patients with brain tumors did not change with the chosen AC method. Quantitative accuracy of SUVs was clinically acceptable for UTE- and BD-AC for group A, whereas for group B BD was in accordance with CTref. Nevertheless, for the quantification of individual lesions large deviations to CTref can be observed independent of the MR-AC method used. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Errors in MR-based attenuation correction for brain imaging with PET/MR scanners

NASA Astrophysics Data System (ADS)

Rota Kops, Elena; Herzog, Hans

2013-02-01

AimAttenuation correction of PET data acquired by hybrid MR/PET scanners remains a challenge, even if several methods for brain and whole-body measurements have been developed recently. A template-based attenuation correction for brain imaging proposed by our group is easy to handle and delivers reliable attenuation maps in a short time. However, some potential error sources are analyzed in this study. We investigated the choice of template reference head among all the available data (error A), and possible skull anomalies of the specific patient, such as discontinuities due to surgery (error B). Materials and methodsAn anatomical MR measurement and a 2-bed-position transmission scan covering the whole head and neck region were performed in eight normal subjects (4 females, 4 males). Error A: Taking alternatively one of the eight heads as reference, eight different templates were created by nonlinearly registering the images to the reference and calculating the average. Eight patients (4 females, 4 males; 4 with brain lesions, 4 w/o brain lesions) were measured in the Siemens BrainPET/MR scanner. The eight templates were used to generate the patients' attenuation maps required for reconstruction. ROI and VOI atlas-based comparisons were performed employing all the reconstructed images. Error B: CT-based attenuation maps of two volunteers were manipulated by manually inserting several skull lesions and filling a nasal cavity. The corresponding attenuation coefficients were substituted with the water's coefficient (0.096/cm). ResultsError A: The mean SUVs over the eight templates pairs for all eight patients and all VOIs did not differ significantly one from each other. Standard deviations up to 1.24% were found. Error B: After reconstruction of the volunteers' BrainPET data with the CT-based attenuation maps without and with skull anomalies, a VOI-atlas analysis was performed revealing very little influence of the skull lesions (less than 3%), while the filled nasal cavity yielded an overestimation in cerebellum up to 5%. ConclusionsThe present error analysis confirms that our template-based attenuation method provides reliable attenuation corrections of PET brain imaging measured in PET/MR scanners.

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PubMed

Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

2010-05-01

The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

Advantages in functional imaging of the brain.

PubMed

Mier, Walter; Mier, Daniela

2015-01-01

As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this-visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine.

FDG-PET study of patients with Leigh syndrome.

PubMed

Haginoya, Kauzhiro; Kaneta, Tomohiro; Togashi, Noriko; Hino-Fukuyo, Naomi; Kobayashi, Tomoko; Uematsu, Mitsugu; Kitamura, Taro; Inui, Takehiko; Okubo, Yukimune; Takezawa, Yusuke; Anzai, Mai; Endo, Wakaba; Miyake, Noriko; Saitsu, Hirotomo; Matsumoto, Naomichi; Kure, Shigeo

2016-03-15

We conducted a [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) study in five patients (median age 11 (range 4-13) years) with Leigh syndrome to evaluate its usefulness for understanding the functional brain dysfunction in this disease and in future drug trials. Four patients were found to have reported mitochondrial DNA gene mutations. The brain T2-weighted magnetic resonance imaging (MRI) showed high-intensity areas in the putamen bilaterally in five patients, caudate bilaterally in four, thalamus bilaterally in two, and brainstem in one. Cerebellar atrophy was observed in older two patients. For disease control, seven age-matched epilepsy patients who had normal MRI and FDG-PET studies were selected. For semiquantitative analysis of the lesions with decreased (18)F-FDG uptake, the mean standard uptake value (SUV) was calculated in regions of interest (ROIs) placed in each brain structure. We compared the SUV of nine segments (the frontal, temporal, parietal, and occipital lobes, thalami, basal ganglia, mid-brain, pons, and cerebellum) between patients with Leigh syndrome and controls. The glucose uptake was decreased significantly in the cerebellum and basal ganglia, which could explain the ataxia and dystonia in patients with Leigh syndrome. Although this study had some limitations, FDG-PET might be useful for evaluating the brain dysfunction and treatment efficacy of new drugs in patients with Leigh syndrome. Further study with more patients using advanced methods to quantify glucose uptake is needed before drawing a conclusion. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry.

PubMed

Henderson, Fiona; Hart, Philippa J; Pradillo, Jesus M; Kassiou, Michael; Christie, Lidan; Williams, Kaye J; Boutin, Herve; McMahon, Adam

2018-05-15

Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In vivo positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex vivo tool for brain recovery imaging. Magnetic resonance imaging (MRI) was used to image a rat brain 48 h after ischaemic stroke to locate the infarcted regions of the brain. PET was carried out 3 months post-stroke using the tracers [ 18 F]DPA-714 for TSPO and [ 18 F]IAM6067 for sigma-1 receptors to image neuroinflammation and neurodegeneration, respectively. The rat brain was flash-frozen immediately after PET scanning, and sectioned for matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging. Three months post-stroke, PET imaging shows minimal detection of neurodegeneration and neuroinflammation, indicating that the brain has stabilised. However, MALDI-MS images reveal distinct differences in lipid distributions (e.g. phosphatidylcholine and sphingomyelin) between the scar and the healthy brain, suggesting that recovery processes are still in play. It is currently not known if the altered lipids in the scar will change on a longer time scale, or if they are stabilised products of the brain post-stroke. The data demonstrates the ability to combine MALD-MS with in vivo PET to image different aspects of stroke recovery. Copyright © 2018 John Wiley & Sons, Ltd.

Study of tonotopic brain changes with functional MRI and FDG-PET in a patient with unilateral objective cochlear tinnitus.

PubMed

Guinchard, A-C; Ghazaleh, Naghmeh; Saenz, M; Fornari, E; Prior, J O; Maeder, P; Adib, S; Maire, R

2016-11-01

We studied possible brain changes with functional MRI (fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a rare, high-intensity "objective tinnitus" (high-level SOAEs) in the left ear of 10 years duration, with no associated hearing loss. This is the first case of objective cochlear tinnitus to be investigated with functional neuroimaging. The objective cochlear tinnitus was measured by Spontaneous Otoacoustic Emissions (SOAE) equipment (frequency 9689 Hz, intensity 57 dB SPL) and is clearly audible to anyone standing near the patient. Functional modifications in primary auditory areas and other brain regions were evaluated using 3T and 7T fMRI and FDG-PET. In the fMRI evaluations, a saturation of the auditory cortex at the tinnitus frequency was observed, but the global cortical tonotopic organization remained intact when compared to the results of fMRI of healthy subjects. The FDG-PET showed no evidence of an increase or decrease of activity in the auditory cortices or in the limbic system as compared to normal subjects. In this patient with high-intensity objective cochlear tinnitus, fMRI and FDG-PET showed no significant brain reorganization in auditory areas and/or in the limbic system, as reported in the literature in patients with chronic subjective tinnitus. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

ViRPET--combination of virtual reality and PET brain imaging

DOEpatents

Majewski, Stanislaw; Brefczynski-Lewis, Julie

2017-05-23

Various methods, systems and apparatus are provided for brain imaging during virtual reality stimulation. In one example, among others, a system for virtual ambulatory environment brain imaging includes a mobile brain imager configured to obtain positron emission tomography (PET) scans of a subject in motion, and a virtual reality (VR) system configured to provide one or more stimuli to the subject during the PET scans. In another example, a method for virtual ambulatory environment brain imaging includes providing stimulation to a subject through a virtual reality (VR) system; and obtaining a positron emission tomography (PET) scan of the subject while moving in response to the stimulation from the VR system. The mobile brain imager can be positioned on the subject with an array of imaging photodetector modules distributed about the head of the subject.

Quantitative Evaluation of Atlas-based Attenuation Correction for Brain PET in an Integrated Time-of-Flight PET/MR Imaging System.

PubMed

Yang, Jaewon; Jian, Yiqiang; Jenkins, Nathaniel; Behr, Spencer C; Hope, Thomas A; Larson, Peder E Z; Vigneron, Daniel; Seo, Youngho

2017-07-01

Purpose To assess the patient-dependent accuracy of atlas-based attenuation correction (ATAC) for brain positron emission tomography (PET) in an integrated time-of-flight (TOF) PET/magnetic resonance (MR) imaging system. Materials and Methods Thirty recruited patients provided informed consent in this institutional review board-approved study. All patients underwent whole-body fluorodeoxyglucose PET/computed tomography (CT) followed by TOF PET/MR imaging. With use of TOF PET data, PET images were reconstructed with four different attenuation correction (AC) methods: PET with patient CT-based AC (CTAC), PET with ATAC (air and bone from an atlas), PET with ATAC patientBone (air and tissue from the atlas with patient bone), and PET with ATAC boneless (air and tissue from the atlas without bone). For quantitative evaluation, PET mean activity concentration values were measured in 14 1-mL volumes of interest (VOIs) distributed throughout the brain and statistical significance was tested with a paired t test. Results The mean overall difference (±standard deviation) of PET with ATAC compared with PET with CTAC was -0.69 kBq/mL ± 0.60 (-4.0% ± 3.2) (P < .001). The results were patient dependent (range, -9.3% to 0.57%) and VOI dependent (range, -5.9 to -2.2). In addition, when bone was not included for AC, the overall difference of PET with ATAC boneless (-9.4% ± 3.7) was significantly worse than that of PET with ATAC (-4.0% ± 3.2) (P < .001). Finally, when patient bone was used for AC instead of atlas bone, the overall difference of PET with ATAC patientBone (-1.5% ± 1.5) improved over that of PET with ATAC (-4.0% ± 3.2) (P < .001). Conclusion ATAC in PET/MR imaging achieves similar quantification accuracy to that from CTAC by means of atlas-based bone compensation. However, patient-specific anatomic differences from the atlas causes bone attenuation differences and misclassified sinuses, which result in patient-dependent performance variation of ATAC. © RSNA, 2017 Online supplemental material is available for this article.

Impact of PET/CT system, reconstruction protocol, data analysis method, and repositioning on PET/CT precision: An experimental evaluation using an oncology and brain phantom.

PubMed

Mansor, Syahir; Pfaehler, Elisabeth; Heijtel, Dennis; Lodge, Martin A; Boellaard, Ronald; Yaqub, Maqsood

2017-12-01

In longitudinal oncological and brain PET/CT studies, it is important to understand the repeatability of quantitative PET metrics in order to assess change in tracer uptake. The present studies were performed in order to assess precision as function of PET/CT system, reconstruction protocol, analysis method, scan duration (or image noise), and repositioning in the field of view. Multiple (repeated) scans have been performed using a NEMA image quality (IQ) phantom and a 3D Hoffman brain phantom filled with 18 F solutions on two systems. Studies were performed with and without randomly (< 2 cm) repositioning the phantom and all scans (12 replicates for IQ phantom and 10 replicates for Hoffman brain phantom) were performed at equal count statistics. For the NEMA IQ phantom, we studied the recovery coefficients (RC) of the maximum (SUV max ), peak (SUV peak ), and mean (SUV mean ) uptake in each sphere as a function of experimental conditions (noise level, reconstruction settings, and phantom repositioning). For the 3D Hoffman phantom, the mean activity concentration was determined within several volumes of interest and activity recovery and its precision was studied as function of experimental conditions. The impact of phantom repositioning on RC precision was mainly seen on the Philips Ingenuity PET/CT, especially in the case of smaller spheres (< 17 mm diameter, P < 0.05). This effect was much smaller for the Siemens Biograph system. When exploring SUV max , SUV peak , or SUV mean of the spheres in the NEMA IQ phantom, it was observed that precision depended on phantom repositioning, reconstruction algorithm, and scan duration, with SUV max being most and SUV peak least sensitive to phantom repositioning. For the brain phantom, regional averaged SUVs were only minimally affected by phantom repositioning (< 2 cm). The precision of quantitative PET metrics depends on the combination of reconstruction protocol, data analysis methods and scan duration (scan statistics). Moreover, precision was also affected by phantom repositioning but its impact depended on the data analysis method in combination with the reconstructed voxel size (tissue fraction effect). This study suggests that for oncological PET studies the use of SUV peak may be preferred over SUV max because SUV peak is less sensitive to patient repositioning/tumor sampling. © 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: Single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM

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

Mathias, C.J.; Welch, M.J.; Raichle, M.E.

1990-03-01

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), copper(II) pyruvaldehyde bis(N4-dimethylthiosemicarbazone) (Cu-PTSM2), and copper(II) ethylglyoxal bis(N4-methylthiosemicarbazone) (Cu-ETSM), have been proposed as PET tracers for cerebral blood flow (CBF) when labeled with generator-produced 62Cu (t1/2 = 9.7 min). To evaluate the potential of Cu-PTSM for CBF PET studies, baboon single-pass cerebral extraction measurements and PET imaging were carried out with the use of 67Cu (t1/2 = 2.6 days) and 64Cu (t1/2 = 12.7 hr), respectively. All three chelates were extracted into the brain with high efficiency. There was some clearance of all chelates in the 10-50-sec time frame and Cu-PTSM2 continued to clear. Cu-PTSM andmore » Cu-ETSM have high residual brain activity. PET imaging of baboon brain was carried out with the use of (64Cu)-Cu-PTSM. For comparison with the 64Cu brain image, a CBF (15O-labeled water) image (40 sec) was first obtained. Qualitatively, the H2(15)O and (64Cu)-Cu-PTSM images were very similar; for example, a comparison of gray to white matter uptake resulted in ratios of 2.42 for H2(15)O and 2.67 for Cu-PTSM. No redistribution of 64Cu was observed in 2 hr of imaging, as was predicted from the single-pass study results. Quantitative determination of blood flow using Cu-PTSM showed good agreement with blood flow determined with H2(15)O. This data suggests that (62Cu)-Cu-PTSM may be a useful generator-produced radiopharmaceutical for blood flow studies with PET.« less

Performance evaluation of neuro-PET using silicon photomultipliers

NASA Astrophysics Data System (ADS)

Jung, Jiwoong; Choi, Yong; Jung, Jin Ho; Kim, Sangsu; Im, Ki Chun

2016-05-01

Recently, we have developed the second prototype Silicon photomultiplier (SiPM) based positron emission tomography (PET) scanner for human brain imaging. The PET system was comprised of detector block which consisted of 4×4 SiPMs and 4×4 Lutetium Yttrium Orthosilicate arrays, charge signal transmission method, high density position decoder circuit and FPGA-embedded ADC boards. The purpose of this study was to evaluate the performance of the newly developed neuro-PET system. The energy resolution, timing resolution, spatial resolution, sensitivity, stability of the photo-peak position and count rate performance were measured. Tomographic image of 3D Hoffman brain phantom was also acquired to evaluate imaging capability of the neuro-PET. The average energy and timing resolutions measured for 511 keV gamma rays were 17±0.1% and 3±0.3 ns, respectively. Spatial resolution and sensitivity at the center of field of view (FOV) were 3.1 mm and 0.8%, respectively. The average scatter fraction was 0.4 with an energy window of 350-650 keV. The maximum true count rate and maximum NECR were measured as 43.3 kcps and 6.5 kcps at an activity concentration of 16.7 kBq/ml and 5.5 kBq/ml, respectively. Long-term stability results show that there was no significant change in the photo-peak position, energy resolution and count rate for 60 days. Phantom imaging studies were performed and they demonstrated the feasibility for high quality brain imaging. The performance tests and imaging results indicate that the newly developed PET is useful for brain imaging studies, if the axial FOV is extended to improve the system sensitivity.

PET evaluation of late cerebral effect in advanced radiation therapy techniques for cranial base tumors.

PubMed

Alongi, Pierpaolo; Iaccarino, Leonardo; Losa, Marco; Del Vecchio, Antonella; Gerevini, Simonetta; Plebani, Valentina; Di Muzio, Nadia; Mortini, Pietro; Gianolli, Luigi; Perani, Daniela

2018-05-25

Even though the benefits of radiation therapy are well established, it is important to recognize the broad spectrum of radiation-induced changes, particularly in the central nervous system. The possible damage to the brain parenchyma may have clinical consequences and in particular cognitive impairment might be one of the major complication of radiotherapy. To date, no studies have investigated the effects of focal radiation therapy on brain structure and function together with the assessment of their clinical outcomes at a long follow-up. In this prospective study, we evaluated in six patients the possible brain late effects after radiation therapy, using a standardized neuropsychological battery, MRI and 18F-FDG PET using SPM and semi-quantitative methods, in patients affected by cranial base tumors who underwent gamma knife or tomotherapy. Neuropsychological examinations showed no cognitive impairment after the treatment. In all patients, both MRI assessment and 18F-FDG-PET did not reveal any local or distant anatomical and metabolic late effects. The present study support the safety of advanced radiation therapy techniques. 18F-FDG-PET, using SPM and semi-quantitative methods, might be a valuable tool to evaluate the cerebral radiotoxicity in patients treated for brain neoplasms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Lou, K; Rice University, Houston, TX; Sun, X

Purpose: To study the feasibility of clinical on-line proton beam range verification with PET imaging Methods: We simulated a 179.2-MeV proton beam with 5-mm diameter irradiating a PMMA phantom of human brain size, which was then imaged by a brain PET with 300*300*100-mm{sup 3} FOV and different system sensitivities and spatial resolutions. We calculated the mean and standard deviation of positron activity range (AR) from reconstructed PET images, with respect to different data acquisition times (from 5 sec to 300 sec with 5-sec step). We also developed a technique, “Smoothed Maximum Value (SMV)”, to improve AR measurement under a givenmore » dose. Furthermore, we simulated a human brain irradiated by a 110-MeV proton beam of 50-mm diameter with 0.3-Gy dose at Bragg peak and imaged by the above PET system with 40% system sensitivity at the center of FOV and 1.7-mm spatial resolution. Results: MC Simulations on the PMMA phantom showed that, regardless of PET system sensitivities and spatial resolutions, the accuracy and precision of AR were proportional to the reciprocal of the square root of image count if image smoothing was not applied. With image smoothing or SMV method, the accuracy and precision could be substantially improved. For a cylindrical PMMA phantom (200 mm diameter and 290 mm long), the accuracy and precision of AR measurement could reach 1.0 and 1.7 mm, with 100-sec data acquired by the brain PET. The study with a human brain showed it was feasible to achieve sub-millimeter accuracy and precision of AR measurement with acquisition time within 60 sec. Conclusion: This study established the relationship between count statistics and the accuracy and precision of activity-range verification. It showed the feasibility of clinical on-line BR verification with high-performance PET systems and improved AR measurement techniques. Cancer Prevention and Research Institute of Texas grant RP120326, NIH grant R21CA187717, The Cancer Center Support (Core) Grant CA016672 to MD Anderson Cancer Center.« less

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.

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

Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke.

PubMed

Nieto, Elena; Delgado, Mercedes; Sobrado, Mónica; de Ceballos, María L; Alajarín, Ramón; García-García, Luis; Kelly, James; Lizasoain, Ignacio; Pozo, Miguel A; Álvarez-Builla, Julio

2015-08-28

The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for further development in ischemic stroke. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans

PubMed Central

Weiner, Michael W.; Aisen, Paul S.; Jack, Clifford R.; Jagust, William J.; Trojanowski, John Q.; Shaw, Leslie; Saykin, Andrew J.; Morris, John C.; Cairns, Nigel; Beckett, Laurel A.; Toga, Arthur; Green, Robert; Walter, Sarah; Soares, Holly; Snyder, Peter; Siemers, Eric; Potter, William; Cole, Patricia E.; Schmidt, Mark

2010-01-01

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer’s disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD. PMID:20451868

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.

Towards Implementing an MR-based PET Attenuation Correction Method for Neurological Studies on the MR-PET Brain Prototype

PubMed Central

Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J.; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A. Gregory

2013-01-01

A number of factors have to be considered for implementing an accurate attenuation correction (AC) in a combined MR-PET scanner. In this work, some of these challenges were investigated and an AC method based entirely on the MR data obtained with a single dedicated sequence was developed and used for neurological studies performed with the MR-PET human brain scanner prototype. Methods The focus was on the bone/air segmentation problem, the bone linear attenuation coefficient selection and the RF coil positioning. The impact of these factors on the PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultra-short echo time (DUTE) MR sequence was proposed for head imaging. Simultaneous MR-PET data were acquired and the PET images reconstructed using the proposed MR-DUTE-based AC method were compared with the PET images reconstructed using a CT-based AC. Results Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm−1 to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. Based on these results, the segmented CT AC method was established as the “silver standard” for the segmented MR-based AC method. Particular to an integrated MR-PET scanner, ignoring the RF coil attenuation can cause large underestimations (i.e. up to 50%) in the reconstructed images. Furthermore, the coil location in the PET field of view has to be accurately known. Good quality bone/air segmentation can be performed using the DUTE data. The PET images obtained using the MR-DUTE- and CT-based AC methods compare favorably in most of the brain structures. Conclusion An MR-DUTE-based AC method was implemented considering all these factors and our preliminary results suggest that this method could potentially be as accurate as the segmented CT method and it could be used for quantitative neurological MR-PET studies. PMID:20810759

Toward implementing an MRI-based PET attenuation-correction method for neurologic studies on the MR-PET brain prototype.

PubMed

Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A Gregory

2010-09-01

Several factors have to be considered for implementing an accurate attenuation-correction (AC) method in a combined MR-PET scanner. In this work, some of these challenges were investigated, and an AC method based entirely on the MRI data obtained with a single dedicated sequence was developed and used for neurologic studies performed with the MR-PET human brain scanner prototype. The focus was on the problem of bone-air segmentation, selection of the linear attenuation coefficient for bone, and positioning of the radiofrequency coil. The impact of these factors on PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultrashort echo time (DUTE) MRI sequence was proposed for head imaging. Simultaneous MR-PET data were acquired, and the PET images reconstructed using the proposed DUTE MRI-based AC method were compared with the PET images that had been reconstructed using a CT-based AC method. Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm(-1) to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. On the basis of these results, the segmented CT AC method was established as the silver standard for the segmented MRI-based AC method. For an integrated MR-PET scanner, in particular, ignoring the radiofrequency coil attenuation can cause large underestimations (i.e.,

Improved frame-based estimation of head motion in PET brain imaging

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

Mukherjee, J. M., E-mail: joyeeta.mitra@umassmed.edu; Lindsay, C.; King, M. A.

Purpose: Head motion during PET brain imaging can cause significant degradation of image quality. Several authors have proposed ways to compensate for PET brain motion to restore image quality and improve quantitation. Head restraints can reduce movement but are unreliable; thus the need for alternative strategies such as data-driven motion estimation or external motion tracking. Herein, the authors present a data-driven motion estimation method using a preprocessing technique that allows the usage of very short duration frames, thus reducing the intraframe motion problem commonly observed in the multiple frame acquisition method. Methods: The list mode data for PET acquisition ismore » uniformly divided into 5-s frames and images are reconstructed without attenuation correction. Interframe motion is estimated using a 3D multiresolution registration algorithm and subsequently compensated for. For this study, the authors used 8 PET brain studies that used F-18 FDG as the tracer and contained minor or no initial motion. After reconstruction and prior to motion estimation, known motion was introduced to each frame to simulate head motion during a PET acquisition. To investigate the trade-off in motion estimation and compensation with respect to frames of different length, the authors summed 5-s frames accordingly to produce 10 and 60 s frames. Summed images generated from the motion-compensated reconstructed frames were then compared to the original PET image reconstruction without motion compensation. Results: The authors found that our method is able to compensate for both gradual and step-like motions using frame times as short as 5 s with a spatial accuracy of 0.2 mm on average. Complex volunteer motion involving all six degrees of freedom was estimated with lower accuracy (0.3 mm on average) than the other types investigated. Preprocessing of 5-s images was necessary for successful image registration. Since their method utilizes nonattenuation corrected frames, it is not susceptible to motion introduced between CT and PET acquisitions. Conclusions: The authors have shown that they can estimate motion for frames with time intervals as short as 5 s using nonattenuation corrected reconstructed FDG PET brain images. Intraframe motion in 60-s frames causes degradation of accuracy to about 2 mm based on the motion type.« less

Improved frame-based estimation of head motion in PET brain imaging

PubMed Central

Mukherjee, J. M.; Lindsay, C.; Mukherjee, A.; Olivier, P.; Shao, L.; King, M. A.; Licho, R.

2016-01-01

Purpose: Head motion during PET brain imaging can cause significant degradation of image quality. Several authors have proposed ways to compensate for PET brain motion to restore image quality and improve quantitation. Head restraints can reduce movement but are unreliable; thus the need for alternative strategies such as data-driven motion estimation or external motion tracking. Herein, the authors present a data-driven motion estimation method using a preprocessing technique that allows the usage of very short duration frames, thus reducing the intraframe motion problem commonly observed in the multiple frame acquisition method. Methods: The list mode data for PET acquisition is uniformly divided into 5-s frames and images are reconstructed without attenuation correction. Interframe motion is estimated using a 3D multiresolution registration algorithm and subsequently compensated for. For this study, the authors used 8 PET brain studies that used F-18 FDG as the tracer and contained minor or no initial motion. After reconstruction and prior to motion estimation, known motion was introduced to each frame to simulate head motion during a PET acquisition. To investigate the trade-off in motion estimation and compensation with respect to frames of different length, the authors summed 5-s frames accordingly to produce 10 and 60 s frames. Summed images generated from the motion-compensated reconstructed frames were then compared to the original PET image reconstruction without motion compensation. Results: The authors found that our method is able to compensate for both gradual and step-like motions using frame times as short as 5 s with a spatial accuracy of 0.2 mm on average. Complex volunteer motion involving all six degrees of freedom was estimated with lower accuracy (0.3 mm on average) than the other types investigated. Preprocessing of 5-s images was necessary for successful image registration. Since their method utilizes nonattenuation corrected frames, it is not susceptible to motion introduced between CT and PET acquisitions. Conclusions: The authors have shown that they can estimate motion for frames with time intervals as short as 5 s using nonattenuation corrected reconstructed FDG PET brain images. Intraframe motion in 60-s frames causes degradation of accuracy to about 2 mm based on the motion type. PMID:27147355

Oncologic PET/MRI, part 1: tumors of the brain, head and neck, chest, abdomen, and pelvis.

PubMed

Buchbender, Christian; Heusner, Till A; Lauenstein, Thomas C; Bockisch, Andreas; Antoch, Gerald

2012-06-01

In oncology, staging forms the basis for prognostic consideration and directly influences patient care by determining the therapeutic approach. Cross-sectional imaging techniques, especially when combined with PET information, play an important role in cancer staging. With the recent introduction of integrated whole-body PET/MRI into clinical practice, a novel metabolic-anatomic imaging technique is now available. PET/MRI seems to be highly accurate in T-staging of tumor entities for which MRI has traditionally been favored, such as squamous cell carcinomas of the head and neck. By adding functional MRI to PET, PET/MRI may further improve diagnostic accuracy in the differentiation of scar tissue from recurrence of tumors such as rectal cancer. This hypothesis will have to be assessed in future studies. With regard to N-staging, PET/MRI does not seem to provide a considerable benefit as compared with PET/CT but provides similar N-staging accuracy when applied as a whole-body staging approach. M-staging will benefit from MRI accuracy in the brain and the liver. The purpose of this review is to summarize the available first experiences with PET/MRI and to outline the potential value of PET/MRI in oncologic applications for which data on PET/MRI are still lacking.

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

PubMed

Bauer, Julia; Chen, Wenjing; Nischwitz, Sebastian; Liebl, Jakob; Rieken, Stefan; Welzel, Thomas; Debus, Juergen; Parodi, Katia

2018-04-24

A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques.

PubMed

Noda, Akihiro; Fushiki, Hiroshi; Murakami, Yoshihiro; Sasaki, Hiroshi; Miyoshi, Sosuke; Kakuta, Hirotoshi; Nishimura, Shintaro

2012-11-01

Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT(1)) receptor (AT(1)R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using (11)C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Three male rhesus macaques were bolus intravenously administered [(11)C]telmisartan either alone or as a mixture with unlabeled telmisartan (1mg/kg). Dynamic PET images were acquired for 95min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Telmisartan penetrated into the brain little but enough to block AT(1)R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT(1)R distribution was noted over the entire brain, even on tracer alone dosing. Telmisartan penetrated into the brain enough to block AT(1)R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs. Copyright © 2012 Elsevier Inc. All rights reserved.

Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma-A Pilot Study.

PubMed

Sasikumar, Arun; Kashyap, Raghava; Joy, Ajith; Charan Patro, Kanhu; Bhattacharya, Parthasarathy; Reddy Pilaka, Venkata Krishna; Oommen, Karuna Elza; Pillai, Maroor Raghavan Ambikalmajan

2018-06-22

Imaging of gliomas remains challenging. The aim of the study was to assess the feasibility of using Ga-PSMA-11 PET/CT for imaging gliomas. Fifteen patients with glioma from 2 centers were included in the study. Ten patients were treated cases of glioblastoma with suspected recurrence. Two patients were sent for assessing the nature (primary lesion/metastasis) of space-occupying lesion in the brain; 3 patients were imaged immediately after surgery and before radiotherapy. Target-to-background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. Among the 10 cases with suspected recurrence, scan was positive in 9, subsequent surgery was done, and histopathology proved it to be true recurrence. In the scan-negative case on follow-up, no evidence of disease could be made clinically or radiologically. Among the other cases the presence or absence of disease could be unequivocally identified on the Ga-PSMA-11 brain scan and correlated with the histopathology or other imaging. Apart from the visual assessment quantitative assessment of the lesions with TBR also showed a significantly high TBR value for those with true disease compared with those with no disease. In the evaluation of gliomas, Ga-PSMA-11 PET/CT brain imaging is a potentially useful imaging tool. The use of Ga-PSMA-11 brain PET/CT in evaluation of recurrent glioma seems promising. Absence of physiological uptake of Ga-PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of glioma lesions.

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

PubMed Central

Manning, Kathryn Y.; Rajakumar, Nagalingam; Gómez, Francisco A.; Soddu, Andrea; Borrie, Michael J.

2017-01-01

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1–42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD. PMID:28582450

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease.

PubMed

Kazemifar, Samaneh; Manning, Kathryn Y; Rajakumar, Nagalingam; Gómez, Francisco A; Soddu, Andrea; Borrie, Michael J; Menon, Ravi S; Bartha, Robert

2017-01-01

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.

Automated movement correction for dynamic PET/CT images: evaluation with phantom and patient data.

PubMed

Ye, Hu; Wong, Koon-Pong; Wardak, Mirwais; Dahlbom, Magnus; Kepe, Vladimir; Barrio, Jorge R; Nelson, Linda D; Small, Gary W; Huang, Sung-Cheng

2014-01-01

Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers.

Automated Movement Correction for Dynamic PET/CT Images: Evaluation with Phantom and Patient Data

PubMed Central

Ye, Hu; Wong, Koon-Pong; Wardak, Mirwais; Dahlbom, Magnus; Kepe, Vladimir; Barrio, Jorge R.; Nelson, Linda D.; Small, Gary W.; Huang, Sung-Cheng

2014-01-01

Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers. PMID:25111700

PET examination in intracranial tumor diagnosis of a cat

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

Angyal, G.; Csepura, G.; Balkay, L.

2008-12-08

This paper shows the significance of the Positron Emission Tomography (PET) in the veterinary medication through a case study of a cat brain tumor. A castrated male cat with bilateral mydriasis and blindness arrived at the veterinary clinic. After physical, laboratory and neurological investigations other sickness was ruled out and the inkling of the intracranial lesion had come to light. Brain tumor seemed the most likely to cause the illness because other symptoms appeared (for example: anorexia, depression) and they progrediated fast. PET examination, using {sup 18}F-FDG isotope, was performed to confirm the possible causes of the cat's symptoms.

PET examination in intracranial tumor diagnosis of a cat

NASA Astrophysics Data System (ADS)

Angyal, G.; Csepura, G.; Balkay, L.; Galuska, L.; Molnár, J.; Valastyán, I.

2008-12-01

This paper shows the significance of the Positron Emission Tomography (PET) in the veterinary medication through a case study of a cat brain tumor. A castrated male cat with bilateral mydriasis and blindness arrived at the veterinary clinic. After physical, laboratory and neurological investigations other sickness was ruled out and the inkling of the intracranial lesion had come to light. Brain tumor seemed the most likely to cause the illness because other symptoms appeared (for example: anorexia, depression) and they progrediated fast. PET examination, using 18F-FDG isotope, was performed to confirm the possible causes of the cat's symptoms

Subclinical seizures as a pitfall in 18F-FDG PET imaging of temporal lobe epilepsy.

PubMed

Tafti, Bashir Akhavan; Mandelkern, Mark; Berenji, Gholam Reza

2014-09-01

A 61-year-old man with history of heroin abuse, hepatitis B, hepatitis C, and hypertension was evaluated for seizures. MRI findings were concerning for temporal epilepsy. A brain 18F-FDG PET study showed a hypermetabolic focus in the left temporal lobe, although the patient was asymptomatic during the scan. Later review of electroencephalography recordings revealed a subclinical seizure during imaging. A whole-body 18F-FDG PET scan performed 4 days later for cancer screening purposes, during which the electroencephalography tracings were normal, showed no abnormal metabolic activity in the brain.

Amyloid positron emission tomography in sporadic cerebral amyloid angiopathy: A systematic critical update.

PubMed

Farid, Karim; Charidimou, Andreas; Baron, Jean-Claude

2017-01-01

Sporadic cerebral amyloid angiopathy (CAA) is a very common small vessel disease of the brain, showing preferential and progressive amyloid-βdeposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex. CAA now encompasses not only a specific cerebrovascular pathological trait, but also different clinical syndromes - including spontaneous lobar intracerebral haemorrhage (ICH), dementia and 'amyloid spells' - an expanding spectrum of brain parenchymal MRI lesions and a set of diagnostic criteria - the Boston criteria, which have resulted in increasingly detecting CAA during life. Although currently available validated diagnostic criteria perform well in multiple lobar ICH, a formal diagnosis is currently lacking unless a brain biopsy is performed. This is partly because in practice CAA MRI biomarkers provide only indirect evidence for the disease. An accurate diagnosis of CAA in different clinical settings would have substantial impact for ICH risk stratification and antithrombotic drug use in elderly people, but also for sample homogeneity in drug trials. It has recently been demonstrated that vascular (in addition to parenchymal) amyloid-βdeposition can be detected and quantified in vivo by positron emission tomography (PET) amyloid tracers. This non-invasive approach has the potential to provide a molecular signature of CAA, and could in turn have major clinical impact. However, several issues around amyloid-PET in CAA remain unsettled and hence its diagnostic utility is limited. In this article we systematically review and critically appraise the published literature on amyloid-PET (PiB and other tracers) in sporadic CAA. We focus on two key areas: (a) the diagnostic utility of amyloid-PET in CAA and (b) the use of amyloid-PET as a window to understand pathophysiological mechanism of the disease. Key issues around amyloid-PET imaging in CAA, including relevant technical aspects are also covered in depth. A total of six small-scale studies have addressed (or reported data useful to address) the diagnostic utility of late-phase amyloid PET imaging in CAA, and one additional study dealt with early PiB images as a proxy of brain perfusion. Across these studies, amyloid PET imaging has definite diagnostic utility (currently tested only in probable CAA): it helps rule out CAA if negative, whether compared to healthy controls or to hypertensive deep ICH controls. If positive, however, differentiation from underlying incipient Alzheimer's disease (AD) can be challenging and so far, no approach (regional values, ratios, visual assessment) seems sufficient and specific enough, although early PiB data seem to hold promise. Based on the available evidence reviewed, we suggest a tentative diagnostic flow algorithm for amyloid-PET use in the clinical setting of suspected CAA, combining early- and late-phase PiB-PET images. We also identified ten mechanistic amyloid-PET studies providing early but promising proof-of-concept data on CAA pathophysiology and its various manifestations including key MRI lesions, cognitive impairment and large scale brain alterations. Key open questions that should be addressed in future studies of amyloid-PET imaging in CAA are identified and highlighted.

[(18)F]Florbetaben: a review in β-amyloid PET imaging in cognitive impairment.

PubMed

Syed, Yahiya Y; Deeks, Emma

2015-07-01

Intravenous (18)F-labelled florbetaben ([(18)F]florbetaben) [Neuraceq™] is a polyethylene glycol stilbene derivative that is approved in the USA, EU and South Korea for positron emission tomography (PET) imaging of the brain. It is used to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive impairment. In vitro, [(18)F]florbetaben has high affinity and selectivity for β-amyloid. It has a short PET scan time (15-20 min). Visual assessment of regional and whole brain [(18)F]florbetaben PET images detected brain β-amyloid with high sensitivity and specificity, with good inter-reader agreement, in a phase III study in patients with various levels of cognitive function when compared with postmortem histopathological assessment. The whole brain visual assessment displayed high positive and negative predictive values, enabling amyloid pathology to be reliably detected or excluded. Quantitative PET analyses were generally consistent with the visual assessments. [(18)F]florbetaben was generally well tolerated in clinical trials. All adverse reactions in [(18)F]florbetaben recipients were mild to moderate in severity and the most common were injection-site-related (erythema, irritation and pain). There were no serious adverse reactions related to [(18)F]florbetaben. In summary, [(18)F]florbetaben is a highly accurate β-amyloid PET tracer that has the potential to support the clinical diagnosis of Alzheimer's disease and other causes of cognitive decline.

Fusion of PET and MRI for Hybrid Imaging

NASA Astrophysics Data System (ADS)

Cho, Zang-Hee; Son, Young-Don; Kim, Young-Bo; Yoo, Seung-Schik

Recently, the development of the fusion PET-MRI system has been actively studied to meet the increasing demand for integrated molecular and anatomical imaging. MRI can provide detailed anatomical information on the brain, such as the locations of gray and white matter, blood vessels, axonal tracts with high resolution, while PET can measure molecular and genetic information, such as glucose metabolism, neurotransmitter-neuroreceptor binding and affinity, protein-protein interactions, and gene trafficking among biological tissues. State-of-the-art MRI systems, such as the 7.0 T whole-body MRI, now can visualize super-fine structures including neuronal bundles in the pons, fine blood vessels (such as lenticulostriate arteries) without invasive contrast agents, in vivo hippocampal substructures, and substantia nigra with excellent image contrast. High-resolution PET, known as High-Resolution Research Tomograph (HRRT), is a brain-dedicated system capable of imaging minute changes of chemicals, such as neurotransmitters and -receptors, with high spatial resolution and sensitivity. The synergistic power of the two, i.e., ultra high-resolution anatomical information offered by a 7.0 T MRI system combined with the high-sensitivity molecular information offered by HRRT-PET, will significantly elevate the level of our current understanding of the human brain, one of the most delicate, complex, and mysterious biological organs. This chapter introduces MRI, PET, and PET-MRI fusion system, and its algorithms are discussed in detail.

PET studies in epilepsy

PubMed Central

Sarikaya, Ismet

2015-01-01

Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced 11C-flumazenil (GABAA-cBDZ) and 18F-MPPF (5-HT1A serotonin) and increased 11C-cerfentanil (mu opiate) and 11C-MeNTI (delta opiate) bindings in the area of seizure. 11C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that 11C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous sclerosis complex. 15O-H2O PET was reported to have a similar sensitivity to FDG-PET in detecting epileptic foci. PMID:26550535

Optimising rigid motion compensation for small animal brain PET imaging

NASA Astrophysics Data System (ADS)

Spangler-Bickell, Matthew G.; Zhou, Lin; Kyme, Andre Z.; De Laat, Bart; Fulton, Roger R.; Nuyts, Johan

2016-10-01

Motion compensation (MC) in PET brain imaging of awake small animals is attracting increased attention in preclinical studies since it avoids the confounding effects of anaesthesia and enables behavioural tests during the scan. A popular MC technique is to use multiple external cameras to track the motion of the animal’s head, which is assumed to be represented by the motion of a marker attached to its forehead. In this study we have explored several methods to improve the experimental setup and the reconstruction procedures of this method: optimising the camera-marker separation; improving the temporal synchronisation between the motion tracker measurements and the list-mode stream; post-acquisition smoothing and interpolation of the motion data; and list-mode reconstruction with appropriately selected subsets. These techniques have been tested and verified on measurements of a moving resolution phantom and brain scans of an awake rat. The proposed techniques improved the reconstructed spatial resolution of the phantom by 27% and of the rat brain by 14%. We suggest a set of optimal parameter values to use for awake animal PET studies and discuss the relative significance of each parameter choice.

Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action.

PubMed

Nicolas, Jean-Marie; Hannestad, Jonas; Holden, Daniel; Kervyn, Sophie; Nabulsi, Nabeel; Tytgat, Dominique; Huang, Yiyun; Chanteux, Hugues; Staelens, Ludovicus; Matagne, Alain; Mathy, François-Xavier; Mercier, Joël; Stockis, Armel; Carson, Richard E; Klitgaard, Henrik

2016-02-01

Rapid distribution to the brain is a prerequisite for antiepileptic drugs used for treatment of acute seizures. The preclinical studies described here investigated the high-affinity synaptic vesicle glycoprotein 2A (SV2A) antiepileptic drug brivara-cetam (BRV) for its rate of brain penetration and its onset of action. BRV was compared with levetiracetam (LEV). In vitro permeation studies were performed using Caco-2 cells. Plasma and brain levels were measured over time after single oral dosing to audiogenic mice and were correlated with anticonvulsant activity. Tissue distribution was investigated after single dosing to rat (BRV and LEV) and dog (LEV only). Positron emission tomography (PET) displacement studies were performed in rhesus monkeys using the SV2A PET tracer [11C]UCB-J. The time course of PET tracer displacement was measured following single intravenous (IV) dosing with LEV or BRV. Rodent distribution data and physiologically based pharmacokinetic (PBPK) modeling were used to compute blood-brain barrier permeability (permeability surface area product, PS) values and then predict brain kinetics in man. In rodents, BRV consistently showed a faster entry into the brain than LEV; this correlated with a faster onset of action against seizures in audiogenic susceptible mice. The higher permeability of BRV was also demonstrated in human cells in vitro. PBPK modeling predicted that, following IV dosing to human subjects, BRV might distribute to the brain within a few minutes compared with approximately 1 h for LEV (PS of 0.315 and 0.015 ml/min/g for BRV and LEV, respectively). These data were supported by a nonhuman primate PET study showing faster SV2A occupancy by BRV compared with LEV. These preclinical data demonstrate that BRV has rapid brain entry and fast brain SV2A occupancy, consistent with the fast onset of action in the audiogenic seizure mice assay. The potential benefit of BRV for treatment of acute seizures remains to be confirmed in clinical studies. © 2015 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

[Positron emission tomography in the diagnosis of recurrent growth of brain tumors].

PubMed

Skvortsova, T Iu; Brodskaia, Z L; Rudas, M S; Mozhaev, S V; Gurchin, A F; Medvedev, S V

2005-01-01

The authors analyzed the results of 11C-methionine positron emission tomography (PET) in 101 patients with suspected recurrent brain tumor. The diagnosis was confirmed in 72 patients. The increased 11C-methionine uptake in the initial tumor area is considered to be a crucial PET evidence of a recurrent tumor. On the other hand, brain tissue histological changes associated with surgery, radiation, and chemotherapy were characterized by the low uptake of the tracer. The sensitivity and specificity of PET scanning in detecting tumor recurrence were found to be 95.8 and 96.5%, respectively. 11C-methionine PET is proposed as a reliable technique for early differentiating between a recurrent brain tumor and treatment-induced nonneoplastic changes.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

PubMed

Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

PubMed Central

Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

[11C]PF-3274167 as a PET radiotracer of oxytocin receptors: Radiosynthesis and evaluation in rat brain.

PubMed

Vidal, Benjamin; Karpenko, Iuliia A; Liger, François; Fieux, Sylvain; Bouillot, Caroline; Billard, Thierry; Hibert, Marcel; Zimmer, Luc

2017-12-01

Oxytocin plays a major role in the regulation of social interactions in mammals by interacting with the oxytocin receptor (OTR) expressed in the brain. Furthermore, the oxytocin system appears as a possible therapeutic target in autism spectrum disorders and other psychiatric troubles, justifying current pharmacological researches. Since no specific PET radioligand is currently available to image OTR in the brain, the aim of this study was to radiolabel the specific OTR antagonist PF-3274167 and to evaluate [ 11 C]PF-3274167 as a potential PET tracer for OTR in rat brains. [ 11 C]PF-3274167 was prepared via the O-methylation of its desmethyl precursor with [ 11 C]methyl iodide. The lipophilicity of the radioactive compound was evaluated by measuring the n-octanol-buffer partition coefficient (logD). Autoradiography experiments were performed on rat brain tissue to evaluate the in vitro distribution of the [ 11 C]PF-3274167. MicroPET experiments were conducted with and without pre-injection of ciclosporin in order to evaluate the influence of the P-glycoprotein (P-gp) on the brain uptake. [ 11 C]PF-3274167 was synthesized with high radiochemical and chemical purities (>95%) and good specific activity. The measured logD was 1.93. In vitro, [ 11 C]PF-3274167 did not show any evidence of specific binding to OTR. PET imaging showed that [ 11 C]PF-3274167 uptake in rat brain was very low in basal conditions but increased significantly after the administration of ciclosporin, suggesting that it is a substrate of the P-gp. In the ciclosporin-pre-injected rat, however, [ 11 C]PF-3274167 distribution did not match with the known distribution of OTR in rats. [ 11 C]PF-3274167 is not a suitable tracer for imaging of OTR in rat brain, probably because of a too low affinity for this receptor in addition to a poor brain penetration. Copyright © 2017 Elsevier Inc. All rights reserved.

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

A 31-Channel MR Brain Array Coil Compatible with Positron Emission Tomography

PubMed Central

Sander, Christin Y.; Keil, Boris; Chonde, Daniel B.; Rosen, Bruce R.; Catana, Ciprian; Wald, Lawrence L.

2014-01-01

Purpose Simultaneous acquisition of MR and PET images requires the placement of the MR detection coil inside the PET detector ring where it absorbs and scatters photons. This constraint is the principal barrier to achieving optimum sensitivity on each modality. Here, we present a 31-channel PET-compatible brain array coil with reduced attenuation but improved MR sensitivity. Methods A series of component tests were performed to identify tradeoffs between PET and MR performance. Aspects studied include the remote positioning of preamplifiers, coax size, coil trace size/material, and plastic housing. We then maximized PET performance at minimal cost to MR sensitivity. The coil was evaluated for MR performance (SNR, g-factor) and PET attenuation. Results The coil design showed an improvement in attenuation by 190% (average) compared to conventional 32-channel arrays, and no loss in MR SNR. Moreover, the 31-channel coil displayed an SNR improvement of 230% (cortical ROI) compared to a PET-optimized 8-channel array with similar attenuation properties. Implementing attenuation correction of the 31-channel array successfully removed PET artifacts, which were comparable to those of the 8-channel array. Conclusion The design of the 31-channel PET-compatible coil enables higher sensitivity for PET/MR imaging, paving the way for novel applications in this hybrid-imaging domain. PMID:25046699

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Suitability of [18F]altanserin and PET to determine 5-HT2A receptor availability in the rat brain: in vivo and in vitro validation of invasive and non-invasive kinetic models.

PubMed

Kroll, Tina; Elmenhorst, David; Matusch, Andreas; Wedekind, Franziska; Weisshaupt, Angela; Beer, Simone; Bauer, Andreas

2013-08-01

While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats. Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals. Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals. [18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.

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.

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

Insights into Intrinsic Brain Networks based on Graph Theory and PET in right- compared to left-sided Temporal Lobe Epilepsy.

PubMed

Vanicek, Thomas; Hahn, Andreas; Traub-Weidinger, Tatjana; Hilger, Eva; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert; Pataraia, Ekaterina; Asenbaum-Nan, Susanne

2016-06-28

The human brain exhibits marked hemispheric differences, though it is not fully understood to what extent lateralization of the epileptic focus is relevant. Preoperative [(18)F]FDG-PET depicts lateralization of seizure focus in patients with temporal lobe epilepsy and reveals dysfunctional metabolic brain connectivity. The aim of the present study was to compare metabolic connectivity, inferred from inter-regional [(18)F]FDG PET uptake correlations, in right-sided (RTLE; n = 30) and left-sided TLE (LTLE; n = 32) with healthy controls (HC; n = 31) using graph theory based network analysis. Comparing LTLE and RTLE and patient groups separately to HC, we observed higher lobar connectivity weights in RTLE compared to LTLE for connections of the temporal and the parietal lobe of the contralateral hemisphere (CH). Moreover, especially in RTLE compared to LTLE higher local efficiency were found in the temporal cortices and other brain regions of the CH. The results of this investigation implicate altered metabolic networks in patients with TLE specific to the lateralization of seizure focus, and describe compensatory mechanisms especially in the CH of patients with RTLE. We propose that graph theoretical analysis of metabolic connectivity using [(18)F]FDG-PET offers an important additional modality to explore brain networks.

Evaluation of MLACF based calculated attenuation brain PET imaging for FDG patient studies

NASA Astrophysics Data System (ADS)

Bal, Harshali; Panin, Vladimir Y.; Platsch, Guenther; Defrise, Michel; Hayden, Charles; Hutton, Chloe; Serrano, Benjamin; Paulmier, Benoit; Casey, Michael E.

2017-04-01

Calculating attenuation correction for brain PET imaging rather than using CT presents opportunities for low radiation dose applications such as pediatric imaging and serial scans to monitor disease progression. Our goal is to evaluate the iterative time-of-flight based maximum-likelihood activity and attenuation correction factors estimation (MLACF) method for clinical FDG brain PET imaging. FDG PET/CT brain studies were performed in 57 patients using the Biograph mCT (Siemens) four-ring scanner. The time-of-flight PET sinograms were acquired using the standard clinical protocol consisting of a CT scan followed by 10 min of single-bed PET acquisition. Images were reconstructed using CT-based attenuation correction (CTAC) and used as a gold standard for comparison. Two methods were compared with respect to CTAC: a calculated brain attenuation correction (CBAC) and MLACF based PET reconstruction. Plane-by-plane scaling was performed for MLACF images in order to fix the variable axial scaling observed. The noise structure of the MLACF images was different compared to those obtained using CTAC and the reconstruction required a higher number of iterations to obtain comparable image quality. To analyze the pooled data, each dataset was registered to a standard template and standard regions of interest were extracted. An SUVr analysis of the brain regions of interest showed that CBAC and MLACF were each well correlated with CTAC SUVrs. A plane-by-plane error analysis indicated that there were local differences for both CBAC and MLACF images with respect to CTAC. Mean relative error in the standard regions of interest was less than 5% for both methods and the mean absolute relative errors for both methods were similar (3.4%  ±  3.1% for CBAC and 3.5%  ±  3.1% for MLACF). However, the MLACF method recovered activity adjoining the frontal sinus regions more accurately than CBAC method. The use of plane-by-plane scaling of MLACF images was found to be a crucial step in order to obtain improved activity estimates. Presence of local errors in both MLACF and CBAC based reconstructions would require the use of a normal database for clinical assessment. However, further work is required in order to assess the clinical advantage of MLACF over CBAC based method.

Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI.

PubMed

Ito, Keiichi; Asano, Yoshitaka; Ikegame, Yuka; Shinoda, Jun

2016-01-01

Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage.

18F-Fluorocholine PET/CT, Brain MRI, and 5-Aminolevulinic Acid for the Assessment of Tumor Resection in High-Grade Glioma.

PubMed

García Vicente, Ana María; Jiménez Aragón, Fátima; Villena Martín, Maikal; Jiménez Londoño, German Andrés; Borrás Moreno, Jose María

2017-06-01

High-grade glioma is a very aggressive and infiltrative tumor in which complete resection is a chance for a better outcome. We present the case of a 57-year-old man with a brain lesion suggestive of high-grade glioma. Brain MRI and F-fluorocholine PET/CT were performed previously to plan the surgery. Surgery was microscope assisted after the administration of 5-aminolevulinic acid. Postsurgery brain MRI and PET were blind evaluated to the surgery results and reported as probably gross total resection.

Classification of Parkinsonian syndromes from FDG-PET brain data using decision trees with SSM/PCA features.

PubMed

Mudali, D; Teune, L K; Renken, R J; Leenders, K L; Roerdink, J B T M

2015-01-01

Medical imaging techniques like fluorodeoxyglucose positron emission tomography (FDG-PET) have been used to aid in the differential diagnosis of neurodegenerative brain diseases. In this study, the objective is to classify FDG-PET brain scans of subjects with Parkinsonian syndromes (Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy) compared to healthy controls. The scaled subprofile model/principal component analysis (SSM/PCA) method was applied to FDG-PET brain image data to obtain covariance patterns and corresponding subject scores. The latter were used as features for supervised classification by the C4.5 decision tree method. Leave-one-out cross validation was applied to determine classifier performance. We carried out a comparison with other types of classifiers. The big advantage of decision tree classification is that the results are easy to understand by humans. A visual representation of decision trees strongly supports the interpretation process, which is very important in the context of medical diagnosis. Further improvements are suggested based on enlarging the number of the training data, enhancing the decision tree method by bagging, and adding additional features based on (f)MRI data.

[Human positron emission tomography with oral 11C-vinpocetine].

PubMed

Vas, Adám; Christer, Halldin; Sóvágó, Judit; Johan, Sandell; Cselényi, Zsolt; Kiss, Béla; Kárpáti, Egon; Lars, Farde; Gulyás, Balázs

2003-11-16

Positron emission tomography (PET) is a useful tool for the investigation of certain physiological changes and for the evaluation of the distribution, and receptor binding of drugs labelled with positron emitting isotopes. Vinpocetine (ethyl-apovincaminate) is a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases. In the clinical practice vinpocetine is usually administered to the patients in intravenous infusion followed by long-term oral treatment. Until presently human data describing vinpocetine's kinetics and brain distribution came from ex vivo (blood, plasma, liquor) and post mortem (brain autoradiography) measurements. The authors wished to investigate the kinetics and distribution of vinpocetine in the brain and body after oral administration with PET in order to prove, that PET is useful in the non-invasive in vivo determination of these parameters. Vinpocetine was labelled with carbon-11 and the radioactivity was measured by PET in the stomach, liver, brain, colon and kidneys in healthy male volunteers. The radioactivity in the blood and urine was also determined. After oral administration, [11C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the oral administration of the labelled drug (average maximum uptake: 0.7% of the administered total dose). Brain distribution was heterogeneous (with preferences in the thalamus, basal ganglia and occipital cortex), similar to the distribution previously reported by the authors after intravenous administration. Vinpocetine, administered orally to human volunteers, readily entered the bloodstream from the stomach and the gastrointestinal tract and thereafter passed the blood-brain barrier and entered the brain. Radioactivity from [11C]vinpocetine was also demonstrated in the kidneys and in urine. The study demonstrates that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally administered labelled drugs active in the central nervous system in the living human body.

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

PubMed

Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann

2003-12-01

There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.

[11C]AZ10419096 - a full antagonist PET radioligand for imaging brain 5-HT1B receptors.

PubMed

Lindberg, Anton; Nag, Sangram; Schou, Magnus; Takano, Akihiro; Matsumoto, Junya; Amini, Nahid; Elmore, Charles S; Farde, Lars; Pike, Victor W; Halldin, Christer

2017-11-01

The serotonergic system is widely present in all regions of the central nervous system (CNS) and plays a key modulatory role in many of its functions. Positron emission tomography (PET) is used to study several serotonin receptors in CNS in vivo. The G-protein coupled receptor 5-HT 1B is mostly present in the occipital cortex and in midbrain and is linked to several psychiatric disorders. There is evidence that agonist PET radioligands for neuroreceptors are more sensitive to endogenous neurotransmitters than antagonists. Our previously developed 5-HT 1B receptor PET radioligand, [ 11 C]AZ10419369, is now considered a partial agonist. In this work we are aiming to develop a full antagonist PET radioligand for imaging brain 5-HT 1B receptors, and evaluate its sensitivity to increased endogenous serotonin concentration. [ 11 C]AZ10419096 was synthesized by rapid methylation of the prepared corresponding N-desmethyl precursor with [ 11 C]methyl triflate. Five PET measurements were performed in cynomolgus monkeys, consisting of two at baseline, one after treatment of a monkey with a 5-HT 1B antagonist, AR-A000002, and two in which fenfluramine was administered during scanning to induce endogenous serotonin release. [ 11 C]AZ10419096 was synthesized in high yield and purity within 30 min, including purification, formulation and sterile filtration. The baseline PET measurements demonstrated [ 11 C]AZ10419096 to have favorable radioligand characteristics, including high specific binding in brain regions that have high 5-HT 1B density, such as occipital cortex and globus pallidus, as well as subsequent rapid elimination from brain and a minor abundance of lipophilic radiometabolites in plasma. AR-A00002 completely blocked radioligand receptor-specific binding. Fenfluramine produced a distinct displacement of radioligand consistent with an expected increase of synaptic endogenous serotonin concentration. [ 11 C]AZ10419096, a full 5-HT 1B antagonist PET radioligand, demonstrates high specific binding in monkey brain that is sensitive to competition from a known 5-HT 1B antagonist as well as to putatively increased endogenous serotonin levels. Published by Elsevier Inc.

Brain and Language.

ERIC Educational Resources Information Center

Damasio, Antonio R., Damasio, Hanna

1992-01-01

Discusses the advances made in understanding the brain structures responsible for language. Presents findings made using magnetic resonance imaging (MRI) and positron emission tomographic (PET) scans to study brain activity. These findings map the structures in the brain that manipulate concepts and those that turn concepts into words. (MCO)

Evaluation of a video-based head motion tracking system for dedicated brain PET

NASA Astrophysics Data System (ADS)

Anishchenko, S.; Beylin, D.; Stepanov, P.; Stepanov, A.; Weinberg, I. N.; Schaeffer, S.; Zavarzin, V.; Shaposhnikov, D.; Smith, M. F.

2015-03-01

Unintentional head motion during Positron Emission Tomography (PET) data acquisition can degrade PET image quality and lead to artifacts. Poor patient compliance, head tremor, and coughing are examples of movement sources. Head motion due to patient non-compliance can be an issue with the rise of amyloid brain PET in dementia patients. To preserve PET image resolution and quantitative accuracy, head motion can be tracked and corrected in the image reconstruction algorithm. While fiducial markers can be used, a contactless approach is preferable. A video-based head motion tracking system for a dedicated portable brain PET scanner was developed. Four wide-angle cameras organized in two stereo pairs are used for capturing video of the patient's head during the PET data acquisition. Facial points are automatically tracked and used to determine the six degree of freedom head pose as a function of time. The presented work evaluated the newly designed tracking system using a head phantom and a moving American College of Radiology (ACR) phantom. The mean video-tracking error was 0.99±0.90 mm relative to the magnetic tracking device used as ground truth. Qualitative evaluation with the ACR phantom shows the advantage of the motion tracking application. The developed system is able to perform tracking with accuracy close to millimeter and can help to preserve resolution of brain PET images in presence of movements.

Brain imaging and cognition in young narcoleptic patients.

PubMed

Huang, Yu-Shu; Liu, Feng-Yuan; Lin, Chin-Yang; Hsiao, Ing-Tsung; Guilleminault, Christian

2016-08-01

The relationship between functional brain images and performances in narcoleptic patients and controls is a new field of investigation. We studied 71 young, type 1 narcoleptic patients and 20 sex- and age-matched control individuals using brain positron emission tomography (PET) images and neurocognitive testing. Clinical investigation was carried out using sleep-wake evaluation questionnaires; a sleep-wake study was conducted with actigraphy, polysomnography, multiple sleep latency test (MSLT), and blood tests (with human leukocyte antigen typing). The continuous performance test (CPT) and Wisconsin card sorting test (WCST) were administered on the same day as the PET study. PET data were analyzed using Statistical Parametric Mapping (version 8) software. Correlation of brain imaging and neurocognitive function was performed by Pearson's correlation. Statistical analyses (Student's t-test) were conducted with SPSS version-18. Seventy-one narcoleptic patients (mean age: 16.15 years, 41 boys (57.7%)) and 20 controls (mean age: 15.1 years, 12 boys (60%)) were studied. Results from the CPT and WCST showed significantly worse scores in narcoleptic patients than in controls (P < 0.05). Compared to controls, narcoleptic patients presented with hypometabolism in the right mid-frontal lobe and angular gyrus (P < 0.05) and significant hypermetabolism in the olfactory lobe, hippocampus, parahippocampus, amygdala, fusiform, left inferior parietal lobe, left superior temporal lobe, striatum, basal ganglia and thalamus, right hypothalamus, and pons (P < 0.05) in the PET study. Changes in brain metabolic activity in narcoleptic patients were positively correlated with results from the sleepiness scales and performance tests. Young, type 1 narcoleptic patients face a continuous cognitive handicap. Our imaging cognitive test protocol can be useful for investigating the effects of treatment trials in these patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Pilot Study on Long Term Effects of HZE Exposure on the Canine Brain

NASA Astrophysics Data System (ADS)

Budinger, T.; Brennan, K.; Pearlstein, R.

A ground-based pilot experiment was initiated in December 1992 to evaluate the long term effects on health and aging after HZE cosmic radiation of the canine brain. Six adult male beagle dogs (1 yr) from the UC Davis breeding colony at the Laboratory for Energy Related Health Research were researched in this study. Iron nuclei at 600 MeV/amu (180 keV/mm) were used to irradiate the whole brain. The fluence of 3 x 106 iron nuclei/ cm2 mimics the HZE exposure (all > He) for a 2- year mission to Mars. The HZE irradiation was a fully stripped iron particle beam at the LBNL BEVALAC. Using a Raster Scanner we were able to spread the beam to deliver a uniform dose over the brain. The total dose to the brain was 200 cGy. Four dogs were whole brain irradiated with iron and two dogs served as litter-mate controls. The control dogs received a similar amount of background neutron irradiation as the irradiated dogs. One of the control dogs died suddenly 3/98 of intestinal cancer unrelated to the brain irradiation. That brain was not harvested before autolysis had prevented analysis. Periodic PET metabolism and yearly MRI studies have been done on these dog's brain since irradiation. All dogs had yearly physical, neurological and blood chemistry work-ups. PET imaging was performed with the Donner 600-crystal high-resolution PET (2.6 mm resolution) and with the commercial PET, CTI/Siemens ECAT 951 PET Scanner (5 mm resolution). NMR imaging is performed with the 1 5T GE Signa at UCSF using T spoiled gradient imaging.1 sequences for T1 contrast at 1 mm resolution as well as a T2 weighted spin echo imaging sequence at 1 mm resolution. A major goal of this work is to present an accurate method for measuring surface areas and volumes of the irradiated vs the non-irradiated canine brain using MRI data which are isotropic in resolution at the 1 mm level. This allows us to monitor the changes in brain size with aging and radiation exposure. Nine years post irradiation, these dog brains (+ 3 additional age-matched controls) were in-situ perfused with 4% paraformaldehyde/01.M phosphate buffer. The brain was removed and fixed in the same fixative for 2 weeks. Brain sections were embedded in parafin and cut at 6 or 12 μm thickness. Histology included H&E, Luxol fast blue and Silver staining. Immunochemistry included Amyloidprecursor protein. There was no marked increase in amyloid plaque formation in the irradiated dogs. Imaging and histology results will be presented at the COSPAR conference.

High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

NASA Astrophysics Data System (ADS)

Naidoo-Variawa, S.; Hey-Cunningham, A. J.; Lehnert, W.; Kench, P. L.; Kassiou, M.; Banati, R.; Meikle, S. R.

2007-11-01

The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm3 FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm3) and 3D reprojection (3DRP) (5.9-9.1 mm3). A pilot 18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy.

PubMed

Naddaf, Sleiman Y; Syed, Ghulam Mustafa Shah; Hadb, Abdulrahman; Al-Thaqfi, Saif

2016-09-01

We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs.

Compact and mobile high resolution PET brain imager

DOEpatents

Majewski, Stanislaw [Yorktown, VA; Proffitt, James [Newport News, VA

2011-02-08

A brain imager includes a compact ring-like static PET imager mounted in a helmet-like structure. When attached to a patient's head, the helmet-like brain imager maintains the relative head-to-imager geometry fixed through the whole imaging procedure. The brain imaging helmet contains radiation sensors and minimal front-end electronics. A flexible mechanical suspension/harness system supports the weight of the helmet thereby allowing for patient to have limited movements of the head during imaging scans. The compact ring-like PET imager enables very high resolution imaging of neurological brain functions, cancer, and effects of trauma using a rather simple mobile scanner with limited space needs for use and storage.

Influence of Dexamethasone on O-(2-[18F]-Fluoroethyl)-L-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake.

PubMed

Stegmayr, Carina; Stoffels, Gabriele; Kops, Elena Rota; Lohmann, Philipp; Galldiks, Norbert; Shah, Nadim J; Neumaier, Bernd; Langen, Karl-Josef

2018-05-29

O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [ 18 F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR). [ 18 F]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [ 18 F]FET uptake in the normal brain (SUV brain ) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy. SUV brain of [ 18 F]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUV brain 1.33 ± 0.1 versus 1.06 ± 0.16 in male and 1.45 ± 0.25 versus 1.31 ± 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUV brain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBR max and TBR mean , which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBR max and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUV brain . Dexamethasone treatment appears to increase the [ 18 F]FET uptake in the normal brain. An effect on TBR max , TBR mean , and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [ 18 F]FET PET.

Preclinical Efficacy of the Anti-Hepatocyte Growth Factor Antibody Ficlatuzumab in a Mouse Brain Orthotopic Glioma Model Evaluated by Bioluminescence, PET, and MRI

PubMed Central

Mittra, Erik S.; Fan-Minogue, Hua; Lin, Frank I.; Karamchandani, Jason; Sriram, Venkataraman; Han, May; Gambhir, Sanjiv S.

2016-01-01

Purpose Ficlatuzumab is a novel therapeutic agent targeting the hepatocyte growth factor (HGF)/c-MET pathway. We summarize extensive preclinical work using this agent in a mouse brain orthotopic model of glioblastoma. Experimental Design Sequential experiments were done using eight- to nine-week-old nude mice injected with 3 × 105 U87 MG (glioblastoma) cells into the brain. Evaluation of ficlatuzumab dose response for this brain tumor model and comparison of its response to ficlatuzumab and to temozolamide were conducted first. Subsequently, various small-animal imaging modalities, including bioluminescence imaging (BLI), positron emission tomography (PET), and MRI, were used with a U87 MG-Luc 2 stable cell line, with and without the use of ficlatuzumab, to evaluate the ability to non-invasively assess tumor growth and response to therapy. ANOVA was conducted to evaluate for significant differences in the response. Results There was a survival benefit with ficlatuzumab alone or in combination with temozolamide. BLI was more sensitive than PET in detecting tumor cells. Fluoro-D-thymidine (FLT) PET provided a better signal-to-background ratio than 2[18F]fluoro-2-deoxy-D-glucose (FDG) PET. In addition, both BLI and FLT PET showed significant changes over time in the control group as well as with response to therapy. MRI does not disclose any time-dependent change. Also, the MRI results showed a temporal delay in comparison to the BLI and FLT PET findings, showing similar results one drug cycle later. Conclusions Targeting the HGF/c-MET pathway with the novel agent ficlatuzumab appears promising for the treatment of glioblastoma. Various clinically applicable imaging modalities including FLT, PET, and MRI provide reliable ways of assessing tumor growth and response to therapy. Given the clinical applicability of these findings, future studies on patients with glioblastoma may be appropriate. PMID:23983258

Effects of anesthetic protocol on normal canine brain uptake of 18F-FDG assessed by PET/CT.

PubMed

Lee, Min Su; Ko, Jeff; Lee, Ah Ra; Lee, In Hye; Jung, Mi Ae; Austin, Brenda; Chung, Hyunwoo; Nahm, Sangsoep; Eom, Kidong

2010-01-01

The purpose of this study was to assess the effects of four anesthetic protocols on normal canine brain uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) using positron emission tomography/computed tomography (PET/CT). Five clinically normal beagle dogs were anesthetized with (1) propofol/isoflurane, (2) medetomidine/pentobarbital, (3) xylazine/ketamine, and (4) medetomidine/tiletamine-zolazepam in a randomized cross-over design. The standard uptake value (SUV) of FDG was obtained in the frontal, parietal, temporal and occipital lobes, cerebellum, brainstem and whole brain, and compared within and between anesthetic protocols using the Friedman test with significance set at P < 0.05. Significant differences in SUVs were observed in various part of the brain associated with each anesthetic protocol. The SUV for the frontal and occipital lobes was significantly higher than in the brainstem in all dogs. Dogs receiving medetomidine/tiletamine-zolazepam also had significantly higher whole brain SUVs than the propofol/isoflurane group. We concluded that each anesthetic protocol exerted a different regional brain glucose uptake pattern. As a result, when comparing brain glucose uptake using PET/CT, one should consider the effects of anesthetic protocols on different regions of the glucose uptake in the dog's brain.

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.

Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity

NASA Astrophysics Data System (ADS)

Fukuta, Tatsuya; Asai, Tomohiro; Ishii, Takayuki; Koide, Hiroyuki; Kiyokawa, Chiaki; Hashimoto, Masahiro; Kikuchi, Takashi; Shimizu, Kosuke; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

2016-07-01

The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain.

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

A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

PubMed

Park, Hae-Jeong; Park, Bumhee; Kim, Hae Yu; Oh, Maeng-Keun; Kim, Joong Il; Yoon, Misun; Lee, Jong Doo; Chang, Jin Woo

2015-05-01

As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Comparison of simultaneously recorded [H2(15)O]-PET and LORETA during cognitive and pharmacological activation.

PubMed

Gamma, Alex; Lehmann, Dietrich; Frei, Edi; Iwata, Kazuki; Pascual-Marqui, Roberto D; Vollenweider, Franz X

2004-06-01

The complementary strengths and weaknesses of established functional brain imaging methods (high spatial, low temporal resolution) and EEG-based techniques (low spatial, high temporal resolution) make their combined use a promising avenue for studying brain processes at a more fine-grained level. However, this strategy requires a better understanding of the relationship between hemodynamic/metabolic and neuroelectric measures of brain activity. We investigated possible correspondences between cerebral blood flow (CBF) as measured by [H2O]-PET and intracerebral electric activity computed by Low Resolution Brain Electromagnetic Tomography (LORETA) from scalp-recorded multichannel EEG in healthy human subjects during cognitive and pharmacological stimulation. The two imaging modalities were compared by descriptive, correlational, and variance analyses, the latter carried out using statistical parametric mapping (SPM99). Descriptive visual comparison showed a partial overlap between the sets of active brain regions detected by the two modalities. A number of exclusively positive correlations of neuroelectric activity with regional CBF were found across the whole EEG frequency range, including slow wave activity, the latter finding being in contrast to most previous studies conducted in patients. Analysis of variance revealed an extensive lack of statistically significant correspondences between brain activity changes as measured by PET vs. EEG-LORETA. In general, correspondences, to the extent they were found, were dependent on experimental condition, brain region, and EEG frequency. Copyright 2004 Wiley-Liss, Inc.

A 31-channel MR brain array coil compatible with positron emission tomography.

PubMed

Sander, Christin Y; Keil, Boris; Chonde, Daniel B; Rosen, Bruce R; Catana, Ciprian; Wald, Lawrence L

2015-06-01

Simultaneous acquisition of MR and positron emission tomography (PET) images requires the placement of the MR detection coil inside the PET detector ring where it absorbs and scatters photons. This constraint is the principal barrier to achieving optimum sensitivity on each modality. Here, we present a 31-channel PET-compatible brain array coil with reduced attenuation but improved MR sensitivity. A series of component tests were performed to identify tradeoffs between PET and MR performance. Aspects studied include the remote positioning of preamplifiers, coax size, coil trace size/material, and plastic housing. We then maximized PET performance at minimal cost to MR sensitivity. The coil was evaluated for MR performance (signal to noise ratio [SNR], g-factor) and PET attenuation. The coil design showed an improvement in attenuation by 190% (average) compared with conventional 32-channel arrays, and no loss in MR SNR. Moreover, the 31-channel coil displayed an SNR improvement of 230% (cortical region of interest) compared with a PET-optimized 8-channel array with similar attenuation properties. Implementing attenuation correction of the 31-channel array successfully removed PET artifacts, which were comparable to those of the 8-channel array. The design of the 31-channel PET-compatible coil enables higher sensitivity for PET/MR imaging, paving the way for novel applications in this hybrid-imaging domain. © 2014 Wiley Periodicals, Inc.

Preclinical Characterization of the Phosphodiesterase 10A PET Tracer [(11)C]MK-8193.

PubMed

Hostetler, Eric D; Fan, Hong; Joshi, Aniket D; Zeng, Zhizhen; Eng, Waisi; Gantert, Liza; Holahan, Marie; Meng, Xianjun; Miller, Patricia; O'Malley, Stacey; Purcell, Mona; Riffel, Kerry; Salinas, Cristian; Williams, Mangay; Ma, Bennett; Buist, Nicole; Smith, Sean M; Coleman, Paul J; Cox, Christopher D; Flores, Brock A; Raheem, Izzat T; Cook, Jacquelynn J; Evelhoch, Jeffrey L

2016-08-01

A positron emission tomography (PET) tracer for the enzyme phosphodiesterase 10A (PDE10A) is desirable to guide the discovery and development of PDE10A inhibitors as potential therapeutics. The preclinical characterization of the PDE10A PET tracer [(11)C]MK-8193 is described. In vitro binding studies with [(3)H]MK-8193 were conducted in rat, monkey, and human brain tissue. PET studies with [(11)C]MK-8193 were conducted in rats and rhesus monkeys at baseline and following administration of a PDE10A inhibitor. [(3)H]MK-8193 is a high-affinity, selective PDE10A radioligand in rat, monkey, and human brain tissue. In vivo, [(11)C]MK-8193 displays rapid kinetics, low test-retest variability, and a large specific signal that is displaced by a structurally diverse PDE10A inhibitor, enabling the determination of pharmacokinetic/enzyme occupancy relationships. [(11)C]MK-8193 is a useful PET tracer for the preclinical characterization of PDE10A therapeutic candidates in rat and monkey. Further evaluation of [(11)C]MK-8193 in humans is warranted.

A follow-up ¹⁸F-FDG brain PET study in a case of Hashimoto's encephalopathy causing drug-resistant status epilepticus treated with plasmapheresis.

PubMed

Pari, Elisa; Rinaldi, Fabrizio; Premi, Enrico; Codella, Maria; Rao, Renata; Paghera, Barbara; Panarotto, Maria Beatrice; De Maria, Giovanni; Padovani, Alessandro

2014-04-01

Hashimoto's encephalopathy (HE) is a rare neuropsychiatric syndrome associated with antithyroid antibodies. It may have an acute onset (episodes of cerebral ischemia, seizure, and psychosis) or it may present as an indolent form (depression, cognitive decline, myoclonus, tremors, and fluctuations in level of consciousness). We here describe a case of encephalopathy presenting as non-convulsive status epilepticus associated with Hashimoto's thyroiditis (HT), unresponsive to corticosteroid therapy, with improvement after plasma exchange treatment. A previously healthy 19-year-old woman, presented generalized tonic-clonic seizures. About a month later, she manifested a speech disorder characterized by difficulties in the production and comprehension of language. Within a few days she also developed confusion and difficulties in recognizing familiar places, with gradual worsening over time. EEG revealed a non-convulsive status epilepticus (NCSE). CSF examination showed slightly elevated cell count and four oligoclonal bands. MRI was unremarkable, and (18)F-FDG brain PET showed widespread hypometabolism, mostly in posterior regions bilaterally. Laboratory and ultrasound findings showed signs of HT. Treatment with steroid was introduced without any improvement. After five sessions of plasma exchange there was a decrease of antithyroid antibodies, as well as EEG and clinical improvement. Three months after discharge (18)F-FDG brain PET showed a complete normalization of the picture, and the patient was asymptomatic. This report emphasizes the successful treatment of HE with plasma exchange in a patient who presented with NCSE. Based on the actual evidence, the term "Encephalopathy associated with Hashimoto's thyroiditis" may be the most proper. Furthermore, to our knowledge, this is the first case of an adult patient studied twice with an (18)F-FDG brain PET: prior to treatment with plasma exchange, and at 3 months follow-up when the patient was clinically completely asymptomatic. Studies in more patients are needed to clarify the relevance of (18)F-FDG brain PET as a possible diagnostic tool for HE.

Functional Brain Imaging

PubMed Central

2006-01-01

Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD). Clinical Need: Target Population and Condition Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. The Technology Being Reviewed Functional Brain Imaging Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. Review Strategy The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies. Sample sizes of at least 20 patients (≥ 10 with condition being reviewed). English-language studies. Human studies. Any age. Studying at least one of the following: fMRI, PET, MRS, or MEG. Functional brain imaging modality must be compared with a clearly defined reference standard. Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. Summary of Findings There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another. There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research. Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG. The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy. Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients. There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS. PMID:23074493

Functional brain imaging: an evidence-based analysis.

PubMed

2006-01-01

The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer's disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson's disease (PD). TARGET POPULATION AND CONDITION Alzheimer's disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson's disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. FUNCTIONAL BRAIN IMAGING: Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS'), and retrospective studies.Sample sizes of at least 20 patients (≥ 10 with condition being reviewed).English-language studies.Human studies.Any age.STUDYING AT LEAST ONE OF THE FOLLOWING: fMRI, PET, MRS, or MEG.Functional brain imaging modality must be compared with a clearly defined reference standard.MUST REPORT AT LEAST ONE OF THE FOLLOWING OUTCOMES: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-(18)F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another. There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research. Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG. The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy. Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients. There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS.

Partial volume correction and image analysis methods for intersubject comparison of FDG-PET studies

NASA Astrophysics Data System (ADS)

Yang, Jun

2000-12-01

Partial volume effect is an artifact mainly due to the limited imaging sensor resolution. It creates bias in the measured activity in small structures and around tissue boundaries. In brain FDG-PET studies, especially for Alzheimer's disease study where there is serious gray matter atrophy, accurate estimate of cerebral metabolic rate of glucose is even more problematic due to large amount of partial volume effect. In this dissertation, we developed a framework enabling inter-subject comparison of partial volume corrected brain FDG-PET studies. The framework is composed of the following image processing steps: (1)MRI segmentation, (2)MR-PET registration, (3)MR based PVE correction, (4)MR 3D inter-subject elastic mapping. Through simulation studies, we showed that the newly developed partial volume correction methods, either pixel based or ROI based, performed better than previous methods. By applying this framework to a real Alzheimer's disease study, we demonstrated that the partial volume corrected glucose rates vary significantly among the control, at risk and disease patient groups and this framework is a promising tool useful for assisting early identification of Alzheimer's patients.

Attenuation correction for brain PET imaging using deep neural network based on dixon and ZTE MR images.

PubMed

Gong, Kuang; Yang, Jaewon; Kim, Kyungsang; El Fakhri, Georges; Seo, Youngho; Li, Quanzheng

2018-05-23

Positron Emission Tomography (PET) is a functional imaging modality widely used in neuroscience studies. To obtain meaningful quantitative results from PET images, attenuation correction is necessary during image reconstruction. For PET/MR hybrid systems, PET attenuation is challenging as Magnetic Resonance (MR) images do not reflect attenuation coefficients directly. To address this issue, we present deep neural network methods to derive the continuous attenuation coefficients for brain PET imaging from MR images. With only Dixon MR images as the network input, the existing U-net structure was adopted and analysis using forty patient data sets shows it is superior than other Dixon based methods. When both Dixon and zero echo time (ZTE) images are available, we have proposed a modified U-net structure, named GroupU-net, to efficiently make use of both Dixon and ZTE information through group convolution modules when the network goes deeper. Quantitative analysis based on fourteen real patient data sets demonstrates that both network approaches can perform better than the standard methods, and the proposed network structure can further reduce the PET quantification error compared to the U-net structure. © 2018 Institute of Physics and Engineering in Medicine.

Unlocking the Secrets of the Brain, Part II: A Continuing Look at Techniques for Exploring the Brain.

ERIC Educational Resources Information Center

Powledge, Tabitha M.

1997-01-01

Describes techniques for delving into the brain including positron emission tomography (PET), single photon emission computed tomography (SPECT), electroencephalogram (EEG), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and low-tech indirect studies. (JRH)

Antibody-based in vivo PET imaging detects amyloid-β reduction in Alzheimer transgenic mice after BACE-1 inhibition.

PubMed

Meier, Silvio R; Syvänen, Stina; Hultqvist, Greta; Fang, Xiaotian T; Roshanbin, Sahar; Lannfelt, Lars; Neumann, Ulf; Sehlin, Dag

2018-05-31

Positron emission tomography (PET) used for visualizing amyloid-β (Aβ) pathology has become an important tool for specific clinical diagnosis of Alzheimer's disease (AD). However, all available amyloid PET radioligands, such as [ 11 C]PiB, reflect levels of insoluble Aβ plaques, but do not capture soluble and protofibrillar Aβ forms. When measured with current PET ligands, the plaque load appears to be fairly static during clinical stages of AD, and may not be affected by Aβ reducing treatments. The aim of the present study was to investigate if a novel PET radioligand, based on an antibody directed towards soluble aggregates of Aβ, could be used to detect changes in Aβ levels during disease progression and after treatment with a β-secretase (BACE-1) inhibitor. Methods: One set of transgenic mice (tg-ArcSwe, model of Aβ pathology) aged between 7 and 16 months were PET scanned with the Aβ protofibril selective radioligand [ 124 I]RmAb158-scFv8D3 to follow progression of Aβ pathology in the brain. A second set of tg-ArcSwe mice, aged 10 months, were treated with BACE-1 inhibitor NB-360 for 3 months and compared to an untreated control group. A set of 10 months old tg-ArcSwe mice also underwent PET scanning, acting as a baseline group. Brain tissue was isolated after PET to determine levels of Aβ by ELISA and immunohistochemistry. Results: Concentration of [ 124 I]RmAb158-scFv8D3 in tg-ArcSwe mice, measured in vivo with PET, increased with age and corresponded well with ex vivo autoradiography and Aβ immunohistochemistry. Tg-ArcSwe mice treated with NB-360 showed significantly lower in vivo PET signals than untreated animals, and were similar to the baseline 10 month old animals. The decreased [ 124 I]RmAb158-scFv8D3 concentrations in NB-360 treated mice, quantified with PET, corresponded well with decreased Aβ levels measured in post mortem brain. Conclusion: A number of treatments for AD are currently studied in phase 2 and 3 clinical trials but there are limited possibilities to study their effects on the important, non-fibrillar Aβ forms in vivo. This study demonstrates the ability of the Aβ protofibril selective radioligand [ 124 I]RmAb158-scFv8D3 to follow disease progression and detect treatment effects with PET imaging in tg-ArcSwe mice. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Mind Over Matter: Methamphetamine

MedlinePlus

... If a Person Uses Methamphetamine for a Long Time? Scientists are using brain imaging techniques, like positron emission tomography (called PET for short), to study the brains of human Methamphetamine users. They have ...

Miniature 'Wearable' PET Scanner Ready for Use

ScienceCinema

Vaska, Paul

2017-12-27

Scientists from BNL, Stony Brook University, and collaborators have demonstrated the efficacy of a "wearable" portable PET scanner they've developed for rats. The device will give neuroscientists a new tool for simultaneously studying brain function and behavior in fully awake, moving animals.

Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

PubMed Central

Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

2011-01-01

OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

Deep Learning MR Imaging-based Attenuation Correction for PET/MR Imaging.

PubMed

Liu, Fang; Jang, Hyungseok; Kijowski, Richard; Bradshaw, Tyler; McMillan, Alan B

2018-02-01

Purpose To develop and evaluate the feasibility of deep learning approaches for magnetic resonance (MR) imaging-based attenuation correction (AC) (termed deep MRAC) in brain positron emission tomography (PET)/MR imaging. Materials and Methods A PET/MR imaging AC pipeline was built by using a deep learning approach to generate pseudo computed tomographic (CT) scans from MR images. A deep convolutional auto-encoder network was trained to identify air, bone, and soft tissue in volumetric head MR images coregistered to CT data for training. A set of 30 retrospective three-dimensional T1-weighted head images was used to train the model, which was then evaluated in 10 patients by comparing the generated pseudo CT scan to an acquired CT scan. A prospective study was carried out for utilizing simultaneous PET/MR imaging for five subjects by using the proposed approach. Analysis of covariance and paired-sample t tests were used for statistical analysis to compare PET reconstruction error with deep MRAC and two existing MR imaging-based AC approaches with CT-based AC. Results Deep MRAC provides an accurate pseudo CT scan with a mean Dice coefficient of 0.971 ± 0.005 for air, 0.936 ± 0.011 for soft tissue, and 0.803 ± 0.021 for bone. Furthermore, deep MRAC provides good PET results, with average errors of less than 1% in most brain regions. Significantly lower PET reconstruction errors were realized with deep MRAC (-0.7% ± 1.1) compared with Dixon-based soft-tissue and air segmentation (-5.8% ± 3.1) and anatomic CT-based template registration (-4.8% ± 2.2). Conclusion The authors developed an automated approach that allows generation of discrete-valued pseudo CT scans (soft tissue, bone, and air) from a single high-spatial-resolution diagnostic-quality three-dimensional MR image and evaluated it in brain PET/MR imaging. This deep learning approach for MR imaging-based AC provided reduced PET reconstruction error relative to a CT-based standard within the brain compared with current MR imaging-based AC approaches. © RSNA, 2017 Online supplemental material is available for this article.

Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET.

PubMed

Wang, Ying; Goh, Joshua O; Resnick, Susan M; Davatzikos, Christos

2013-01-01

In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM) and functional (positron emission tomography of regional cerebral blood flow; PET) brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA). We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM), and short-term memory (STM). For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination) as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive status.

How to design PET experiments to study neurochemistry: application to alcoholism.

PubMed

Morris, Evan D; Lucas, Molly V; Petrulli, J Ryan; Cosgrove, Kelly P

2014-03-01

Positron Emission Tomography (PET) (and the related Single Photon Emission Computed Tomography) is a powerful imaging tool with a molecular specificity and sensitivity that are unique among imaging modalities. PET excels in the study of neurochemistry in three ways: 1) It can detect and quantify neuroreceptor molecules; 2) it can detect and quantify changes in neurotransmitters; and 3) it can detect and quantify exogenous drugs delivered to the brain. To carry out any of these applications, the user must harness the power of kinetic modeling. Further, the quality of the information gained is only as good as the soundness of the experimental design. This article reviews the concepts behind the three main uses of PET, the rationale behind kinetic modeling of PET data, and some of the key considerations when planning a PET experiment. Finally, some examples of PET imaging related to the study of alcoholism are discussed and critiqued.

How to Design PET Experiments to Study Neurochemistry: Application to Alcoholism

PubMed Central

Morris, Evan D.; Lucas, Molly V.; Petrulli, J. Ryan; Cosgrove, Kelly P.

2014-01-01

Positron Emission Tomography (PET) (and the related Single Photon Emission Computed Tomography) is a powerful imaging tool with a molecular specificity and sensitivity that are unique among imaging modalities. PET excels in the study of neurochemistry in three ways: 1) It can detect and quantify neuroreceptor molecules; 2) it can detect and quantify changes in neurotransmitters; and 3) it can detect and quantify exogenous drugs delivered to the brain. To carry out any of these applications, the user must harness the power of kinetic modeling. Further, the quality of the information gained is only as good as the soundness of the experimental design. This article reviews the concepts behind the three main uses of PET, the rationale behind kinetic modeling of PET data, and some of the key considerations when planning a PET experiment. Finally, some examples of PET imaging related to the study of alcoholism are discussed and critiqued. PMID:24600335

Simultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation

NASA Astrophysics Data System (ADS)

Reilhac, Anthonin; Boisson, Frédéric; Wimberley, Catriona; Parmar, Arvind; Zahra, David; Hamze, Hasar; Davis, Emma; Arthur, Andrew; Bouillot, Caroline; Charil, Arnaud; Grégoire, Marie-Claude

2016-02-01

In PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies.

Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer's Disease with Positron Emission Tomography.

PubMed

Xie, Fang; Peng, Fangyu

2017-01-01

Aging is a risk factor for Alzheimer's disease (AD). There are changes of brain metabolism and biometal fluxes due to brain aging, which may play a role in pathogenesis of AD. Positron emission tomography (PET) is a versatile tool for tracking alteration of metabolism and biometal fluxes due to brain aging and AD. Age-dependent changes in cerebral glucose metabolism can be tracked with PET using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a radiolabeled glucose analogue, as a radiotracer. Based on different patterns of altered cerebral glucose metabolism, 18F-FDG PET was clinically used for differential diagnosis of AD and Frontotemporal dementia (FTD). There are continued efforts to develop additional radiopharmaceuticals or radiotracers for assessment of age-dependent changes of various metabolic pathways and biometal fluxes due to brain aging and AD with PET. Elucidation of age-dependent changes of brain metabolism and altered biometal fluxes is not only significant for a better mechanistic understanding of brain aging and the pathophysiology of AD, but also significant for identification of new targets for the prevention, early diagnosis, and treatment of AD.

Development of brain PET using GAPD arrays.

PubMed

Jung, Jin Ho; Choi, Yong; Hong, Key Jo; Kang, Jihoon; Hu, Wei; Lim, Hyun Keong; Huh, Yoonsuk; Kim, Sangsu; Jung, Jiwoong; Kim, Kyu Bom

2012-03-01

In recent times, there has been great interest in the use of Geiger-mode avalanche photodiodes (GAPDs) as scintillator readout in positron emission tomography (PET) detectors because of their advantages, such as high gain, compact size, low power consumption, and magnetic field insensitivity. The purpose of this study was to develop a novel PET system based on GAPD arrays for brain imaging. The PET consisted of 72 detector modules arranged in a ring of 330 mm diameter. Each PET module was composed of a 4 × 4 matrix of 3 × 3 × 20 mm(3) cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled with a 4 × 4 array three-side tileable GAPD. The signals from each PET module were fed into preamplifiers using a 3 m long flat cable and then sent to a position decoder circuit (PDC), which output a digital address and an analog pulse of the interacted channel among 64 preamplifier signals transmitted from four PET detector modules. The PDC outputs were fed into field programmable gate array (FPGA)-embedded data acquisition (DAQ) boards. The analog signal was then digitized, and arrival time and energy of the signal were calculated and stored. The energy and coincidence timing resolutions measured for 511 keV gamma rays were 18.4 ± 3.1% and 2.6 ns, respectively. The transaxial spatial resolution and sensitivity in the center of field of view (FOV) were 3.1 mm and 0.32% cps/Bq, respectively. The rods down to a diameter of 2.5 mm were resolved in a hot-rod phantom image, and activity distribution patterns between the white and gray matters in the Hoffman brain phantom were well imaged. Experimental results indicate that a PET system can be developed using GAPD arrays and the GAPD-based PET system can provide high-quality PET imaging.

The MINDView brain PET detector, feasibility study based on SiPM arrays

NASA Astrophysics Data System (ADS)

González, Antonio J.; Majewski, Stan; Sánchez, Filomeno; Aussenhofer, Sebastian; Aguilar, Albert; Conde, Pablo; Hernández, Liczandro; Vidal, Luis F.; Pani, Roberto; Bettiol, Marco; Fabbri, Andrea; Bert, Julien; Visvikis, Dimitris; Jackson, Carl; Murphy, John; O'Neill, Kevin; Benlloch, Jose M.

2016-05-01

The Multimodal Imaging of Neurological Disorders (MINDView) project aims to develop a dedicated brain Positron Emission Tomography (PET) scanner with sufficient resolution and sensitivity to visualize neurotransmitter pathways and their disruptions in mental disorders for diagnosis and follow-up treatment. The PET system should be compact and fully compatible with a Magnetic Resonance Imaging (MRI) device in order to allow its operation as a PET brain insert in a hybrid imaging setup with most MRI scanners. The proposed design will enable the currently-installed MRI base to be easily upgraded to PET/MRI systems. The current design for the PET insert consists of a 3-ring configuration with 20 modules per ring and an axial field of view of ~15 cm and a geometrical aperture of ~33 cm in diameter. When coupled to the new head Radio Frequency (RF) coil, the inner usable diameter of the complete PET-RF coil insert is reduced to 26 cm. Two scintillator configurations have been tested, namely a 3-layer staggered array of LYSO with 1.5 mm pixel size, with 35×35 elements (6 mm thickness each) and a black-painted monolithic LYSO block also covering about 50×50 mm2 active area with 20 mm thickness. Laboratory test results associated with the current MINDView PET module concept are presented in terms of key parameters' optimization, such as spatial and energy resolution, sensitivity and Depth of Interaction (DOI) capability. It was possible to resolve all pixel elements from the three scintillator layers with energy resolutions as good as 10%. The monolithic scintillator showed average detector resolutions varying from 3.5 mm in the entrance layer to better than 1.5 mm near the photosensor, with average energy resolutions of about 17%.

PET Scans Obtained for Evaluation of Cognitive Dysfunction

PubMed Central

Silverman, Daniel H. S.; Mosconi, Lisa; Ercoli, Linda; Chen, W; Small, Gary W.

2015-01-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism with devastating neuropathologic, economic, social and clinical consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are carried out with [18F]fluorodeoxyglucose (FDG) as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility in evaluating patients with cognitive impairment, and in distinguishing among primary neurodegenerative disorders and other etiologies for cognitive decline. In addition to focusing upon the effects on cerebral metabolism examined with FDG PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact upon the enormous human toll exacted by these diseases. PMID:18514081

Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

PubMed

Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

2013-12-01

Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

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.

Effect of MRI acoustic noise on cerebral fludeoxyglucose uptake in simultaneous MR-PET imaging.

PubMed

Chonde, Daniel B; Abolmaali, Nasreddin; Arabasz, Grae; Guimaraes, Alexander R; Catana, Ciprian

2013-05-01

Integrated scanners capable of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquisition are now available for human use. Although the scanners' manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the 2 modalities, the potential physiological inference has not been evaluated. In this study, we have studied the influence of the acoustic noise produced by the magnetic resonance (MR) gradients on brain fludeoxyglucose (FDG) uptake in the Siemens MR-BrainPET prototype. Although particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, 10 healthy volunteers underwent 2 simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a "quiet" (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a "noisy" (test) environment in which MR sequences were run for the entire time. Cortical and subcortical regions of interest were derived from the high-resolution morphological MR data using FreeSurfer. The changes in the FDG uptake in the FreeSurfer-derived regions of interest between the 2 conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The region of interest-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13% [4.73%]) and static (4.18% [2.87%]) images. The SPM8 analysis showed no statistically significant clusters in any images when a P < 0.05 (corrected) was used; however, a P < 0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left, 8.37% [1.55%]; right, 8.20% [1.17%]) but only unilateral increase in the static image (left, 8.68% [3.89%]). Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in the FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation-related) changes in the FDG uptake in this region if the expected effects are of comparable amplitude.

Markerless rat head motion tracking using structured light for brain PET imaging of unrestrained awake small animals

NASA Astrophysics Data System (ADS)

Miranda, Alan; Staelens, Steven; Stroobants, Sigrid; Verhaeghe, Jeroen

2017-03-01

Preclinical positron emission tomography (PET) imaging in small animals is generally performed under anesthesia to immobilize the animal during scanning. More recently, for rat brain PET studies, methods to perform scans of unrestrained awake rats are being developed in order to avoid the unwanted effects of anesthesia on the brain response. Here, we investigate the use of a projected structure stereo camera to track the motion of the rat head during the PET scan. The motion information is then used to correct the PET data. The stereo camera calculates a 3D point cloud representation of the scene and the tracking is performed by point cloud matching using the iterative closest point algorithm. The main advantage of the proposed motion tracking is that no intervention, e.g. for marker attachment, is needed. A manually moved microDerenzo phantom experiment and 3 awake rat [18F]FDG experiments were performed to evaluate the proposed tracking method. The tracking accuracy was 0.33 mm rms. After motion correction image reconstruction, the microDerenzo phantom was recovered albeit with some loss of resolution. The reconstructed FWHM of the 2.5 and 3 mm rods increased with 0.94 and 0.51 mm respectively in comparison with the motion-free case. In the rat experiments, the average tracking success rate was 64.7%. The correlation of relative brain regional [18F]FDG uptake between the anesthesia and awake scan reconstructions was increased from on average 0.291 (not significant) before correction to 0.909 (p  <  0.0001) after motion correction. Markerless motion tracking using structured light can be successfully used for tracking of the rat head for motion correction in awake rat PET scans.

HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

PubMed Central

Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

2010-01-01

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

[Chilean experience with the use of 18F-deoxyglucose positron emission tomography].

PubMed

Massardo, Teresa; Jofré, M Josefina; Sierralta, Paulina; Canessa, José; González, Patricio; Humeres, Pamela; Valdebenito, Robert

2007-03-01

Clinical oncology is the main application of 18F-deoxyglucose (FDG) positron emission tomography (PET). To evaluate the first 1,000 patients studied with FDG PET in Chile. Retrospective analysis of 1,000 patients (aged between 1 and 94 years, 550 females) studied with FDG PET, since 2003. All studies were performed in a high resolution Siemens Ecat-Exact HR (+). All reports were based on the visual analysis of three plane and three-dimensional images. Ninety seven percent of exams were done for oncological indications, mainly lung lesions, lymphoma, colorectal and gastroesophageal, cancer and breast tumors. Only 1% of patients had brain tumors. Non tumor neurological indications corresponded to 1.7%. Cardiac studies were only 0.3% and inflammatory process corresponded to 1%. The 5.6% corresponded to pediatric population. Six percent of patients were aged less than 18 years and in 50% of them, the indication was oncological, mainly lymphomas, brain tumors, endocrine cancers and sarcomas. The remaining 50% had a neurological indications, mainly for refractory epilepsy. PET FDG imaging was effective in the management of diverse diseases of children and adults.

Functional Imaging and Migraine: New Connections?

PubMed Central

Schwedt, Todd J.; Chong, Catherine D.

2015-01-01

Purpose of Review Over the last several years, a growing number of brain functional imaging studies have provided insights into mechanisms underlying migraine. This manuscript reviews the recent migraine functional neuroimaging literature and provides recommendations for future studies that will help fill knowledge gaps. Recent Findings Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have identified brain regions that might be responsible for mediating the onset of a migraine attack and those associated with migraine symptoms. Enhanced activation of brain regions that facilitate processing of sensory stimuli suggests a mechanism by which migraineurs are hypersensitive to visual, olfactory, and cutaneous stimuli. Resting state functional connectivity MRI studies have identified numerous brain regions and functional networks with atypical functional connectivity in migraineurs, suggesting that migraine is associated with aberrant brain functional organization. Summary fMRI and PET studies that have identified brain regions and brain networks that are atypical in migraine have helped to describe the neurofunctional basis for migraine symptoms. Future studies should compare functional imaging findings in migraine to other headache and pain disorders and should explore the utility of functional imaging data as biomarkers for diagnostic and treatment purposes. PMID:25887764

FDG-PET scan shows increased cerebral blood flow in rat after sublingual glycine application

NASA Astrophysics Data System (ADS)

Blagosklonov, Oleg; Podoprigora, Guennady I.; Davani, Siamak; Nartsissov, Yaroslav R.; Comas, Laurent; Boulahdour, Hatem; Cardot, Jean-Claude

2007-02-01

Positron emission tomography (PET) with [18F]-2-fluoro-deoxy-D-glucose (FDG) is being increasingly used in research. Isotope studies may be of help in an assessment of vasoactive potential of newly developed therapeutic preparations, including natural metabolites, like glycine. As a medicine, glycine was recently shown to have a positive therapeutic effect in the treatment of patients with neurological disorders based on vascular disturbances. By previous direct biomicroscopic investigations of pial microvessels in laboratory rats, an expressed vasodilatory effect of topically applied glycine was proved. The aim of this study was to evaluate the influence of glycine on the rat cerebral blood flow (CBF) using FDG-PET scan. A baseline study was started immediately after intravenous injection of 19 MBq of FDG in anesthetized rat. The PET images were acquired twice, one by one during 20 min. Two hours later, after sublingual application of glycine and the second FDG injection, the pair of PET scan was performed during 20 min as well. Finally, 4 days after the first studies, we repeated the PET scans in the same conditions after sublingual application of glycine. The quantitative analysis of FDG volume concentration (Bq/ml) in the rat brain demonstrated that in both studies after glycine administration, the FDG uptake increased at least 1.5 times in comparison with the baseline data. Moreover, the peak of the concentration was coming in more rapidly. These results confirm the enhancing effect of glycine on the rat CBF possibly because of its vasodilatory effect on brain microvessels. Therefore, FDG-PET technique contributes to better understanding of glycine pharmacokinetics.

Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging.

PubMed

Takkinen, Jatta S; López-Picón, Francisco R; Al Majidi, Rana; Eskola, Olli; Krzyczmonik, Anna; Keller, Thomas; Löyttyniemi, Eliisa; Solin, Olof; Rinne, Juha O; Haaparanta-Solin, Merja

2017-08-01

Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo 18 F-FDG and 18 F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with 18 F-FDG and 18 F-DPA-714 with a one-week interval between the scans. Additional TG (n = 52) and WT (n = 29) mice were used for ex vivo studies. In vivo, the 18 F-FDG SUVs were lower and the 18 F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p < 0.05). The ex vivo cerebellum binding ratios supported the results of the in vivo 18 F-DPA-714 studies but not the 18 F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.

Brain 18F-FDG PET in the diagnosis of neurodegenerative dementias: comparison with perfusion SPECT and with clinical evaluations lacking nuclear imaging.

PubMed

Silverman, Daniel H S

2004-04-01

The clinical identification and differential diagnosis of dementias is especially challenging in the early stages, but the need for early, accurate diagnosis has become more important, now that several medications for the treatment of mild to moderate Alzheimer's disease (AD) are available. Many neurodegenerative diseases produce significant brain-function alterations detectable with PET or SPECT even when structural images with CT or MRI reveal no specific abnormalities. (18)F-FDG PET images of AD demonstrate focally decreased cerebral metabolism involving especially the posterior cingulate and neocortical association cortices, while largely sparing the basal ganglia, thalamus, cerebellum, and cortex mediating primary sensory and motor functions. Assessment of the precise diagnostic accuracy of PET had until recently been hindered by the paucity of data on diagnoses made using PET and confirmed by definitive histopathologic examination. In the past few years, however, studies comparing neuropathologic examination with PET have established reliable and consistent accuracy for diagnostic evaluations using PET-accuracies substantially exceeding those of comparable studies of the diagnostic value of SPECT or of both modalities assessed side by side, or of clinical evaluations done without nuclear imaging. Similar data are emerging concerning the prognostic value of (18)F-FDG PET. Improvements in the ability of PET to identify very early changes associated with AD and other neurodegenerative dementias are currently outpacing improvements in therapeutic options, but with advances in potential preventive and disease-modifying treatments appearing imminent, early detection and diagnosis will play an increasing role in the management of dementing illness.

Amnestic MCI Patients' Perspectives toward Disclosure of Amyloid PET Results in a Research Context.

PubMed

Vanderschaeghe, Gwendolien; Schaeverbeke, Jolien; Vandenberghe, Rik; Dierickx, Kris

2017-01-01

Researchers currently are not obligated to share individual research results (IRR) with participants. This non-disclosure policy has been challenged on the basis of participants' rights to be aware and in control of their personal medical information. Here, we determined how patients view disclosure of research PET results of brain amyloid and why they believe it is advantageous or disadvantageous to disclose. As a part of a larger diagnostic trial, we conducted semi-structured interviews with patients with amnestic Mild Cognitive Impairment (aMCI). Participants had the option to receive their brain amyloid PET scan result (i.e., their IRR). Interviews were conducted before they received their IRR. A total of 38 aMCI patients (100% of study participants) wanted to know their IRR. The two most frequently mentioned reasons for choosing IRR disclosure were to better understand their brain health status and to be better able to make informed decisions about future personal arrangements (e.g., inheritance tax, moving into a smaller house, end-of-life decisions, etc.). Emotional risk was mentioned as the primary disadvantage of knowing one's IRR. On the other hand, non-disclosure was considered to be emotionally difficult also, as patients would be uncertain about their future health condition. Many patients diagnosed clinically with aMCI want to know their brain amyloid test results, even though this knowledge may be disadvantageous to them. Knowing what is going on with their health and the ability to make informed decisions about their future were the two principal advantages mentioned for obtaining their amyloid PET results. Because of the overwhelming consensus of aMCI patients was to disclose their brain amyloid PET scan results, researchers should strongly consider releasing this information to research subjects.

5-HT Radioligands for Human Brain Imaging With PET and SPECT

PubMed Central

Paterson, Louise M.; Kornum, Birgitte R.; Nutt, David J.; Pike, Victor W.; Knudsen, Gitte M.

2014-01-01

The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging. PMID:21674551

Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study.

PubMed

Bauer, Martin; Karch, Rudolf; Zeitlinger, Markus; Philippe, Cécile; Römermann, Kerstin; Stanek, Johann; Maier-Salamon, Alexandra; Wadsak, Wolfgang; Jäger, Walter; Hacker, Marcus; Müller, Markus; Langer, Oliver

2015-05-01

As P-glycoprotein (Pgp) inhibition at the blood-brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[(11)C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[(11)C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.

In vivo evaluation of 18F-MNI698: an 18F-labeled radiotracer for imaging of serotonin 4 receptors in brain.

PubMed

Tavares, Adriana Alexandre S; Caillé, Fabien; Barret, Olivier; Papin, Caroline; Lee, Hsiaoju; Morley, Thomas J; Fowles, Krista; Holden, Daniel; Seibyl, John P; Alagille, David; Tamagnan, Gilles D

2014-05-01

Serotonin 4 receptors (5-hydroxytryptamine receptor 4 [5HT4R]) hold promise as a novel therapeutic approach to multiple brain disorders, including Alzheimer and Huntington disease. In vivo imaging of these receptors with selective 5HT4R radiotracers and PET would be valuable to investigate alterations in 5HT4R in different brain disorders and to assist drug discovery. In this study, (18)F-MNI698 was evaluated as a potential PET radiotracer for imaging of 5HT4R in the brain. Eighteen PET studies were performed in 3 adult rhesus monkeys. The radiotracer was administered as a bolus intravenous injection or bolus plus constant infusion (time that would be required to inject the bolus at the infusion rate = 60 min), and arterial blood was collected for data quantification. Kinetic models were used to estimate distribution volumes and binding potentials, for which the cerebellum was used as a reference region. (18)F-MNI698 test-retest variability and upper mass dose limits were determined. Preblocking studies using several doses of SB204070, a selective 5HT4R antagonist, were performed. (18)F-MNI698 avidly entered the monkey brain (peak percentage injected dose of ∼ 6.6%), and its brain distribution was consistent with known 5HT4R densities. At 120 min after bolus injection and after the start of radiotracer infusion, only less than 5% and approximately 10% parent compound was present in blood, respectively. Measured binding potentials were underestimated by 22%-36% when noninvasive methods were used for data quantification in comparison with invasive methods. A good agreement was found between test-retest measurements. The radiotracer upper mass dose limit (<5% occupancy) was determined to be 13.1 μg per 70 kg of body weight. SB204070 blocked the radiotracer binding in a dose-dependent manner. Data indicate that (18)F-MNI698 is a promising PET radiotracer for imaging of 5HT4R in the brain, and human studies are warranted based on these study results.

Analysis of the Metabolic and Structural Brain Changes in Patients With Torture-Related Post-Traumatic Stress Disorder (TR-PTSD) Using 18F-FDG PET and MRI

PubMed Central

Zandieh, Shahin; Bernt, Reinhard; Knoll, Peter; Wenzel, Thomas; Hittmair, Karl; Haller, Joerg; Hergan, Klaus; Mirzaei, Siroos

2016-01-01

Abstract Many people exposed to torture later suffer from torture-related post-traumatic stress disorder (TR-PTSD). The aim of this study was to analyze the morphologic and functional brain changes in patients with TR-PTSD using magnetic resonance imaging (MRI) and positron emission tomography (PET). This study evaluated 19 subjects. Thirteen subcortical brain structures were evaluated using FSL software. On the T1-weighted images, normalized brain volumes were measured using SIENAX software. The study compared the volume of the brain and 13 subcortical structures in 9 patients suffering from TR-PTSD after torture and 10 healthy volunteers (HV). Diffusion-weighted imaging (DWI) was performed in the transverse plane. In addition, the 18F-FDG PET data were evaluated to identify the activity of the elected regions. The mean left hippocampal volume for the TR-PTSD group was significantly lower than in the HV group (post hoc test (Bonferroni) P < 0.001). There was a significant difference between the gray matter volume of the patients with TR-PTSD and the HV group (post hoc test (Bonferroni) P < 0.001). The TR-PTSD group showed low significant expansion of the ventricles in contrast to the HV group (post hoc test (Bonferroni) P < 0.001). Diffusion-weighted imaging revealed significant differences in the right frontal lobe and the left occipital lobe between the TR-PTSD and HV group (post hoc test (Bonferroni) P < 0.001). Moderate hypometabolism was noted in the occipital lobe in 6 of the 9 patients with TR-PTSD, in the temporal lobe in 1 of the 9 patients, and in the caudate nucleus in 5 of the 9 patients. In 2 cases, additional hypometabolism was observed in the posterior cingulate cortex and in the parietal and frontal lobes. The findings from this study show that TR-PTSD might have a deleterious influence on a set of specific brain structures. This study also demonstrated that PET combined with MRI is sensitive in detecting possible metabolic and structural brain changes in TR-PTSD. PMID:27082610

Analysis of the Metabolic and Structural Brain Changes in Patients With Torture-Related Post-Traumatic Stress Disorder (TR-PTSD) Using ¹⁸F-FDG PET and MRI.

PubMed

Zandieh, Shahin; Bernt, Reinhard; Knoll, Peter; Wenzel, Thomas; Hittmair, Karl; Haller, Joerg; Hergan, Klaus; Mirzaei, Siroos

2016-04-01

Many people exposed to torture later suffer from torture-related post-traumatic stress disorder (TR-PTSD). The aim of this study was to analyze the morphologic and functional brain changes in patients with TR-PTSD using magnetic resonance imaging (MRI) and positron emission tomography (PET). This study evaluated 19 subjects. Thirteen subcortical brain structures were evaluated using FSL software. On the T1-weighted images, normalized brain volumes were measured using SIENAX software. The study compared the volume of the brain and 13 subcortical structures in 9 patients suffering from TR-PTSD after torture and 10 healthy volunteers (HV). Diffusion-weighted imaging (DWI) was performed in the transverse plane. In addition, the 18F-FDG PET data were evaluated to identify the activity of the elected regions. The mean left hippocampal volume for the TR-PTSD group was significantly lower than in the HV group (post hoc test (Bonferroni) P < 0.001). There was a significant difference between the gray matter volume of the patients with TR-PTSD and the HV group (post hoc test (Bonferroni) P < 0.001). The TR-PTSD group showed low significant expansion of the ventricles in contrast to the HV group (post hoc test (Bonferroni) P < 0.001). Diffusion-weighted imaging revealed significant differences in the right frontal lobe and the left occipital lobe between the TR-PTSD and HV group (post hoc test (Bonferroni) P < 0.001). Moderate hypometabolism was noted in the occipital lobe in 6 of the 9 patients with TR-PTSD, in the temporal lobe in 1 of the 9 patients, and in the caudate nucleus in 5 of the 9 patients. In 2 cases, additional hypometabolism was observed in the posterior cingulate cortex and in the parietal and frontal lobes. The findings from this study show that TR-PTSD might have a deleterious influence on a set of specific brain structures. This study also demonstrated that PET combined with MRI is sensitive in detecting possible metabolic and structural brain changes in TR-PTSD.

Inter-subject FDG PET Brain Networks Exhibit Multi-scale Community Structure with Different Normalization Techniques.

PubMed

Sperry, Megan M; Kartha, Sonia; Granquist, Eric J; Winkelstein, Beth A

2018-07-01

Inter-subject networks are used to model correlations between brain regions and are particularly useful for metabolic imaging techniques, like 18F-2-deoxy-2-(18F)fluoro-D-glucose (FDG) positron emission tomography (PET). Since FDG PET typically produces a single image, correlations cannot be calculated over time. Little focus has been placed on the basic properties of inter-subject networks and if they are affected by group size and image normalization. FDG PET images were acquired from rats (n = 18), normalized by whole brain, visual cortex, or cerebellar FDG uptake, and used to construct correlation matrices. Group size effects on network stability were investigated by systematically adding rats and evaluating local network connectivity (node strength and clustering coefficient). Modularity and community structure were also evaluated in the differently normalized networks to assess meso-scale network relationships. Local network properties are stable regardless of normalization region for groups of at least 10. Whole brain-normalized networks are more modular than visual cortex- or cerebellum-normalized network (p < 0.00001); however, community structure is similar at network resolutions where modularity differs most between brain and randomized networks. Hierarchical analysis reveals consistent modules at different scales and clustering of spatially-proximate brain regions. Findings suggest inter-subject FDG PET networks are stable for reasonable group sizes and exhibit multi-scale modularity.

Methionine PET/CT Studies In Patients With Cancer

ClinicalTrials.gov

2018-06-15

Brain Tumors and/or Solid Tumors Including; Brain Stem Glioma; High Grade CNS Tumors; Ependymoma; Medulloblastoma; Craniopharyngioma; Low Grade CNS Tumors; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Ewing Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Other

Brain-Based Learning. Research Brief

ERIC Educational Resources Information Center

Walker, Karen

2005-01-01

What does brain-based research say about how adolescents learn? The 1990s was declared as the Decade of the Brain by President Bush and Congress. With the advancement of MRIs (Magnetic Resonance Imagining) and PET (positron emission tomography) scans, it has become much easier to study live healthy brains. As a result, the concept of…

Evaluation of dissemination studies with FDG whole-body positron emission tomography in patients with suspected metastatic tumours of brain and spine.

PubMed

Go, K G; Pruim, J; Que, T H; Vaalburg, W; Haaxma-Reiche, H

2000-01-01

In the preoperative diagnosis of malignant brain tumours there is often uncertainty regarding their metastatic or primary nature, requiring dissemination studies. Currently FDG-wbPET is being used for the efficient detection of systemic tumours. It therefore may become a substitute for the conventional dissemination studies if it allows an earlier diagnosis. In this descriptive and preliminary study a population of 14 patients with suspected or proven metastatic lesions, [18F]-fluoro-2-deoxy-D-glucose whole body positron emission tomography (FDG-wbPET) was conducted and verified by additional conventional dissemination studies. FINDINGS AND THEIR INTERPRETATION: The entire series of dissemination studies required an average of 30 days with a range of 4-73 days. The FDG-wbPET was corroborated by the other dissemination studies in 10 of the 14 patients. In 7 of these 10 patients both PET and dissemination studies showed systemic abnormal findings, but in one case the presence of high pulmonary activity on the FDG-wbPET and the abnormal findings on the chest X-rays proved to be Aspergillus infection at autopsy. In the other 2 cases the negative PET findings corresponded to the absence of systemic dissemination. In 5 cases there was disagreement of the results of the FDG-wbPET with other evidence, among which there were 2 cases of glioblastoma in which systemic metastases were most unlikely, and the foci of activity on the FDG-wbPET had to be considered as false positives. In the remaining 3 cases the systemic presence of high activity on the FDG-wbPET indicated the systemic presence of tumour, whereas the other dissemination studies disclosed no tumour. The results warrant the use of FDG-wbPET as a screening method for the search of metastases, allowing other studies to be focussed on the lesion. But from the cost/benefit point of view this would make the method less suitable as a substitute for dissemination studies in general, although it may speed up the diagnostic process.

A perspective on the future role of brain pet imaging in exercise science.

PubMed

Boecker, Henning; Drzezga, Alexander

2016-05-01

Positron Emission Tomography (PET) bears a unique potential for examining the effects of physical exercise (acute or chronic) within the central nervous system in vivo, including cerebral metabolism, neuroreceptor occupancy, and neurotransmission. However, application of Neuro-PET in human exercise science is as yet surprisingly sparse. To date the field has been dominated by non-invasive neuroelectrical techniques (EEG, MEG) and structural/functional magnetic resonance imaging (sMRI/fMRI). Despite PET having certain inherent disadvantages, in particular radiation exposure and high costs limiting applicability at large scale, certain research questions in human exercise science can exclusively be addressed with PET: The "metabolic trapping" properties of (18)F-FDG PET as the most commonly used PET-tracer allow examining the neuronal mechanisms underlying various forms of acute exercise in a rather unconstrained manner, i.e. under realistic training scenarios outside the scanner environment. Beyond acute effects, (18)F-FDG PET measurements under resting conditions have a strong prospective for unraveling the influence of regular physical activity on neuronal integrity and potentially neuroprotective mechanisms in vivo, which is of special interest for aging and dementia research. Quantification of cerebral glucose metabolism may allow determining the metabolic effects of exercise interventions in the entire human brain and relating the regional cerebral rate of glucose metabolism (rCMRglc) with behavioral, neuropsychological, and physiological measures. Apart from FDG-PET, particularly interesting applications comprise PET ligand studies that focus on dopaminergic and opioidergic neurotransmission, both key transmitter systems for exercise-related psychophysiological effects, including mood changes, reward processing, antinociception, and in its most extreme form 'exercise dependence'. PET ligand displacement approaches even allow quantifying specific endogenous neurotransmitter release under acute exercise interventions, to which modern PET/MR hybrid technology will be additionally fruitful. Experimental studies exploiting the unprecedented multimodal imaging capacities of PET/MR in human exercise sciences are as yet pending. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of Atlas-Based Attenuation Correction for Integrated PET/MR in Human Brain: Application of a Head Atlas and Comparison to True CT-Based Attenuation Correction.

PubMed

Sekine, Tetsuro; Buck, Alfred; Delso, Gaspar; Ter Voert, Edwin E G W; Huellner, Martin; Veit-Haibach, Patrick; Warnock, Geoffrey

2016-02-01

Attenuation correction (AC) for integrated PET/MR imaging in the human brain is still an open problem. In this study, we evaluated a simplified atlas-based AC (Atlas-AC) by comparing (18)F-FDG PET data corrected using either Atlas-AC or true CT data (CT-AC). We enrolled 8 patients (median age, 63 y). All patients underwent clinically indicated whole-body (18)F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MR of the head (additional tracer was not injected). For each patient, 2 AC maps were generated: an Atlas-AC map registered to a patient-specific liver accelerated volume acquisition-Flex MR sequence and using a vendor-provided head atlas generated from multiple CT head images and a CT-based AC map. For comparative AC, the CT-AC map generated from PET/CT was superimposed on the Atlas-AC map. PET images were reconstructed from the list-mode raw data from the PET/MR imaging scanner using each AC map. All PET images were normalized to the SPM5 PET template, and (18)F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative difference (%diff) between images based on Atlas-AC and CT-AC was calculated, and averaged difference images were generated. (18)F-FDG uptake in all VOIs was compared using Bland-Altman analysis. The range of error in all 536 VOIs was -3.0%-7.3%. Whole-brain (18)F-FDG uptake based on Atlas-AC was slightly underestimated (%diff = 2.19% ± 1.40%). The underestimation was most pronounced in the regions below the anterior/posterior commissure line, such as the cerebellum, temporal lobe, and central structures (%diff = 3.69% ± 1.43%, 3.25% ± 1.42%, and 3.05% ± 1.18%), suggesting that Atlas-AC tends to underestimate the attenuation values of the skull base bone. When compared with the gold-standard CT-AC, errors introduced using Atlas-AC did not exceed 8% in any brain region investigated. Underestimation of (18)F-FDG uptake was minor (<4%) but significant in regions near the skull base. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Use of fluorine-18-BPA PET images and image registration to enhance radiation treatment planning for boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Khan, Mohammad Khurram

The Monte-Carlo based simulation environment for radiation therapy (SERA) software is used to simulate the dose administered to a patient undergoing boron neutron capture therapy (BNCT). Point sampling of tumor tissue results in an estimate of a uniform boron concentration scaling factor of 3.5. Under conventional treatment protocols, this factor is used to scale the boron component of the dose linearly and homogenously within the tumor and target volumes. The average dose to the tumor cells by such a method could be improved by better methods of quantifying the in-vivo 10B biodistribution. A better method includes radiolabeling para-Boronophenylalanine (p-BPA) with 18F and imaging the pharmaceutical using positron emission tomography (PET). This biodistribution of 18F-BPA can then be used to better predict the average dose delivered to the tumor regions. This work uses registered 18F-BPA PET images to incorporate the in-vivo boron biodistribution within current treatment planning. The registered 18F-BPA PET images are then coupled in a new computer software, PET2MRI.m, to linearly scale the boron component of the dose. A qualititative and quantitative assessment of the dose contours is presented using the two approaches. Tumor volume, tumor axial extent, and target locations are compared between using MRI or PET images to define the tumor volume. In addition, peak-to-normal brain value at tumor axial center is determined for pre and post surgery patients using 18F-BPA PET images. The differences noted between the registered GBM tumor volumes (range: 34.04--136.36%), tumor axial extent (range: 20--150%), and the beam target location (1.27--4.29 cm) are significantly different. The peak-to-normal brain values are also determined at the tumor axial center using the 18F-BPA PET images. The peak-to-normal brain values using the last frame of the pre-surgery study for the GBM patients ranged from 2.05--3.4. For post surgery time weighted PET data, the peak-to-normal brain value in the residual parts of the tumor ranged from 1.5--1.7. Qualitatively, boron dose contours are greatly shifted using PET images when compared with MRI images. Collectively, these differences can lead to significant reorientation of the beam and can significantly impact current BNCT treatment planning.

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.

Animal imaging studies of potential brain damage

NASA Astrophysics Data System (ADS)

Gatley, S. J.; Vazquez, M. E.; Rice, O.

To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

PubMed

Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

2011-04-01

Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

Ultra low-dose CT attenuation correction in PET SPM

NASA Astrophysics Data System (ADS)

Wang, Shyh-Jen; Yang, Bang-Hung; Tsai, Chia-Jung; Yang, Ching-Ching; Lee, Jason J. S.; Wu, Tung-Hsin

2010-07-01

The use of CT images for attenuation correction (CTAC) allows significantly shorter scanning time and a high quality noise-free attenuation map compared with conventional germanium-68 transmission scan because at least 10 4 times greater of photon flux would be generated from a CT scan under standard operating condition. However, this CTAC technique would potentially introduce more radiation risk to the patients owing to the higher radiation exposure from CT scan. Statistic parameters mapping (SPM) is a prominent technique in nuclear medicine community for the analysis of brain imaging data. The purpose of this study is to assess the feasibility of low-dose CT (LDCT) and ultra low-dose CT (UDCT) in PET SPM applications. The study was divided into two parts. The first part was to evaluate of tracer uptake distribution pattern and quantity analysis by using the striatal phantom to initially assess the feasibility of AC for clinical purpose. The second part was to examine the group SPM analysis using the Hoffman brain phantom. The phantom study is to simulate the human brain and to reduce the experimental uncertainty of real subjects. The initial studies show that the results of PET SPM analysis have no significant differences between LDCT and UDCT comparing to the current used default CTAC. Moreover, the dose of the LDCT is lower than that of the default CT by a factor of 9, and UDCT can even yield a 42 times dose reduction. We have demonstrated the SPM results while using LDCT and UDCT for PET AC is comparable to those using default CT setting, suggesting their feasibility in PET SPM applications. In addition, the necessity of UDCT in PET SPM studies to avoid excess radiation dose is also evident since most of the subjects involved are non-cancer patients or children and some normal subjects are even served as a comparison group in the experiment. It is our belief that additional attempts to decrease the radiation dose would be valuable, especially for children and normal volunteers, to work towards ALARA (as low as reasonably achievable) concept for PET SPM studies.

Age-dependent Changes of Cerebral Copper Metabolism in Atp7b−/− Knockout Mouse Model of Wilson’s Disease by [64Cu]CuCl2-PET/CT

PubMed Central

Xie, Fang; Xi, Yin; Pascual, Juan M.; Muzik, Otto; Peng, Fangyu

2017-01-01

Copper is a nutritional metal required for brain development and function. Wilson’s disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by mutation of ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study is to explore feasibility and use of copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependence changes of cerebral copper metabolism in WD using an Atp7b−/− knockout mouse model of WD and a positron emission tomography/computed tomography (PET/CT) scanner. Continuing from recent study of biodistribution and radiation dosimetry of [64C]CuCl2 in Atp7b−/− knockout mice, PET quantitative analysis revealed low 64Cu radioactivity in the brains of Atp7b−/− knockout mice at 7th week of age, compared with the 64Cu radioactivity in the brains of age and gender-matched wild type C57BL/6 mice, at 24 hour (h) post intravenous injection of [64C]CuCl2 as a tracer. Furthermore, age-dependent increase of 64Cu radioactivity was detected in the brains of Atp7b−/− knockout mice from 13th to 21th week of age, using the data derived from a longitudinal [64C]CuCl2-PET/CT study of Atp7b−/− knockout mice with orally administered [64Cu]CuCl2 as a tracer. The findings of this study support the use of [64Cu]CuCl2-PET/CT as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms. PMID:28130615

Age-dependent changes of cerebral copper metabolism in Atp7b -/- knockout mouse model of Wilson's disease by [64Cu]CuCl2-PET/CT.

PubMed

Xie, Fang; Xi, Yin; Pascual, Juan M; Muzik, Otto; Peng, Fangyu

2017-06-01

Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([ 64 C]CuCl 2 ) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b -/- knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our recent study of biodistribution and radiation dosimetry of [ 64 C]CuCl 2 in Atp7b -/- knockout mice, PET quantitative analysis revealed low 64 Cu radioactivity in the brains of Atp7b -/- knockout mice at 7th weeks of age, compared with 64 Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [ 64 C]CuCl 2 as a tracer. Furthermore, age-dependent increase of 64 Cu radioactivity was detected in the brains of Atp7b -/- knockout mice from the 13th to 21th weeks of age, based on the data derived from a longitudinal [ 64 C]CuCl 2 -PET/CT study of Atp7b -/- knockout mice with orally administered [ 64 Cu]CuCl 2 as a tracer. The findings of this study support clinical use of [ 64 Cu]CuCl 2 -PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

Attenuation correction for the large non-human primate brain imaging using microPET.

PubMed

Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

2010-04-21

Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

Attenuation correction for the large non-human primate brain imaging using microPET

NASA Astrophysics Data System (ADS)

Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

2010-04-01

Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

PubMed Central

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

2011-01-01

Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in brain and peripheral organs. PMID:19217534

Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

PubMed

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

2009-02-01

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in the brain and peripheral organs.

Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

PubMed Central

Ettrup, Anders; da Cunha-Bang, Sophie; McMahon, Brenda; Lehel, Szabolcs; Dyssegaard, Agnete; Skibsted, Anine W; Jørgensen, Louise M; Hansen, Martin; Baandrup, Anders O; Bache, Søren; Svarer, Claus; Kristensen, Jesper L; Gillings, Nic; Madsen, Jacob; Knudsen, Gitte M

2014-01-01

[11C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT2A) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [11C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT2A receptors with [11C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [11C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [11C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT2A receptor antagonist ketanserin before a second PET scan significantly decreased [11C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [11C]Cimbi-36 binding is selective for 5-HT2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT2A receptors in the human brain. Thus, we here describe [11C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT2A receptors in the human brain. PMID:24780897

MR-assisted PET Motion Correction for eurological Studies in an Integrated MR-PET Scanner

PubMed Central

Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Byars, Larry; Hamm, Michael; Chonde, Daniel B.; Michel, Christian J.; El Fakhri, Georges; Schmand, Matthias; Sorensen, A. Gregory

2011-01-01

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MR data can be used for motion tracking. In this work, a novel data processing and rigid-body motion correction (MC) algorithm for the MR-compatible BrainPET prototype scanner is described and proof-of-principle phantom and human studies are presented. Methods To account for motion, the PET prompts and randoms coincidences as well as the sensitivity data are processed in the line or response (LOR) space according to the MR-derived motion estimates. After sinogram space rebinning, the corrected data are summed and the motion corrected PET volume is reconstructed from these sinograms and the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed and motion estimates were obtained using two high temporal resolution MR-based motion tracking techniques. Results After accounting for the physical mismatch between the two scanners, perfectly co-registered MR and PET volumes are reproducibly obtained. The MR output gates inserted in to the PET list-mode allow the temporal correlation of the two data sets within 0.2 s. The Hoffman phantom volume reconstructed processing the PET data in the LOR space was similar to the one obtained processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the novel MC algorithm. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 seconds and 20 ms, respectively. Substantially improved PET images with excellent delineation of specific brain structures were obtained after applying the MC using these MR-based estimates. Conclusion A novel MR-based MC algorithm was developed for the integrated MR-PET scanner. High temporal resolution MR-derived motion estimates (obtained while simultaneously acquiring anatomical or functional MR data) can be used for PET MC. An MR-based MC has the potential to improve PET as a quantitative method, increasing its reliability and reproducibility which could benefit a large number of neurological applications. PMID:21189415

PET brain kinetics studies of 11C-ITMM and 11C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate

PubMed Central

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed 11C-labeled PET probes 11C-ITMM and 11C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared 11C-ITMM and 11C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with 11C-ITDM than with 11C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm-3 for 11C-ITMM and 3.6 mL∙cm-3 for 11C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of 11C-ITMM and 11C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that 11C-ITDM may be superior to 11C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with 11C-ITDM were higher than those of 11C-ITMM. Clinical studies of 11C-ITDM in humans will be necessary in the future. PMID:24795840

PET brain kinetics studies of (11)C-ITMM and (11)C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate.

PubMed

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed (11)C-labeled PET probes (11)C-ITMM and (11)C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared (11)C-ITMM and (11)C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with (11)C-ITDM than with (11)C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm(-3) for (11)C-ITMM and 3.6 mL∙cm(-3) for (11)C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of (11)C-ITMM and (11)C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that (11)C-ITDM may be superior to (11)C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with (11)C-ITDM were higher than those of (11)C-ITMM. Clinical studies of (11)C-ITDM in humans will be necessary in the future.

Evaluation of the default-mode network by quantitative 15O-PET: comparative study between cerebral blood flow and oxygen consumption.

PubMed

Aoe, Jo; Watabe, Tadashi; Shimosegawa, Eku; Kato, Hiroki; Kanai, Yasukazu; Naka, Sadahiro; Matsunaga, Keiko; Isohashi, Kayako; Tatsumi, Mitsuaki; Hatazawa, Jun

2018-06-22

Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO 2 ). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15 O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO 2 to the DMN. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15 O-O 2 , 15 O-CO gases and 15 O-water PET. Quantitative CBF and CMRO 2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson's correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO 2 , respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO 2 . Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO 2 . Among them, 12 overlapping networks were observed between CBF and CMRO 2 . Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO 2 , indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. We estimated the functional correlations in the DMN by means of quantitative PET using 15 O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO 2 , indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

Binding of 2-[18F]fluoro-CP-118,954 to mouse acetylcholinesterase: microPET and ex vivo Cerenkov luminescence imaging studies.

PubMed

Kim, Dong Hyun; Choe, Yearn Seong; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae

2011-05-01

Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/μmol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in γ-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains. Copyright © 2011 Elsevier Inc. All rights reserved.

Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot.

PubMed

Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B; Turkheimer, Federico E

2016-04-15

PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i.e. there were no significant post-transcriptional changes). This condition can be readily established a priori by assessing the correlation between PET and mRNA expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot

PubMed Central

Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B.; Turkheimer, Federico E.

2016-01-01

PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i.e. there were no significant post-transcriptional changes). This condition can be readily established a priori by assessing the correlation between PET and mRNA expression. PMID:26850512

Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

PubMed

Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

2017-06-01

Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular Imaging of Transporters with Positron Emission Tomography

NASA Astrophysics Data System (ADS)

Antoni, Gunnar; Sörensen, Jens; Hall, Håkan

Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug-Pgp interactions, although [11C]verapamil and [18F]fluoropaclitaxel are probably restricted to use in studies of the blood-brain barrier. The vesicular monoamine transporter 2 (VMAT2) is another interesting target for diagnostic imaging and [11C]DTBZ is a promising tracer. The noninvasive imaging of transporter density as a function of disease progression or availability following interaction with blocking drugs is highlighted, including the impact on both development of new therapies and the process of developing new drugs. Although CNS-related work focusing on psychiatric disorders is the main focus of this review, other applications of PET ligands, such as diagnosis of cancer, diabetes research, and drug interactions with efflux systems, are also discussed. The use of PET especially in terms of tracer development is briefly described. Finally, it can be concluded that there is an urgent need for new, selective radioligands for the study of the transporter systems in the human brain using PET.

Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy

NASA Astrophysics Data System (ADS)

Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

2017-03-01

The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET activity distributions was improved by employing a brain specific segmentation applicable to both DECT and SECT data.

Synthesis and Initial in Vivo Studies with [11C]SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3

PubMed Central

2015-01-01

Quantifying glycogen synthase kinase-3 (GSK-3) activity in vivo using positron emission tomography (PET) imaging is of interest because dysregulation of GSK-3 is implicated in numerous diseases and neurological disorders for which GSK-3 inhibitors are being considered as therapeutic strategies. Previous PET radiotracers for GSK-3 have been reported, but none of the published examples cross the blood–brain barrier. Therefore, we have an ongoing interest in developing a brain penetrating radiotracer for GSK-3. To this end, we were interested in synthesis and preclinical evaluation of [11C]SB-216763, a high-affinity inhibitor of GSK-3 (Ki = 9 nM; IC50 = 34 nM). Initial radiosyntheses of [11C]SB-216763 proved ineffective in our hands because of competing [3 + 3] sigmatropic shifts. Therefore, we have developed a novel one-pot two-step synthesis of [11C]SB-216763 from a 2,4-dimethoxybenzyl-protected maleimide precursor, which provided high specific activity [11C]SB-216763 in 1% noncorrected radiochemical yield (based upon [11C]CH3I) and 97–100% radiochemical purity (n = 7). Initial preclinical evaluation in rodent and nonhuman primate PET imaging studies revealed high initial brain uptake (peak rodent SUV = 2.5 @ 3 min postinjection; peak nonhuman primate SUV = 1.9 @ 5 min postinjection) followed by washout. Brain uptake was highest in thalamus, striatum, cortex, and cerebellum, areas known to be rich in GSK-3. These results make the arylindolemaleimide skeleton our lead scaffold for developing a PET radiotracer for quantification of GSK-3 density in vivo and ultimately translating it into clinical use. PMID:26005531

Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

PubMed Central

Hwang, Kristy S.; Avila, David; Elashoff, David; Kohannim, Omid; Teng, Edmond; Sokolow, Sophie; Jack, Clifford R.; Jagust, William J.; Shaw, Leslie; Trojanowski, John Q.; Weiner, Michael W.; Thompson, Paul M.

2015-01-01

Background: The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort. Methods: We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1–42 (Aβ42) ≤192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia. Results: The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%. Conclusions: Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future. Classification of evidence: This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%). PMID:25609767

Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures.

PubMed

Apostolova, Liana G; Hwang, Kristy S; Avila, David; Elashoff, David; Kohannim, Omid; Teng, Edmond; Sokolow, Sophie; Jack, Clifford R; Jagust, William J; Shaw, Leslie; Trojanowski, John Q; Weiner, Michael W; Thompson, Paul M

2015-02-17

The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort. We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1-42 (Aβ42) ≤ 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥ 1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia. The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%. Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future. This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%). © 2015 American Academy of Neurology.

Probabilistic Air Segmentation and Sparse Regression Estimated Pseudo CT for PET/MR Attenuation Correction

PubMed Central

Chen, Yasheng; Juttukonda, Meher; Su, Yi; Benzinger, Tammie; Rubin, Brian G.; Lee, Yueh Z.; Lin, Weili; Shen, Dinggang; Lalush, David

2015-01-01

Purpose To develop a positron emission tomography (PET) attenuation correction method for brain PET/magnetic resonance (MR) imaging by estimating pseudo computed tomographic (CT) images from T1-weighted MR and atlas CT images. Materials and Methods In this institutional review board–approved and HIPAA-compliant study, PET/MR/CT images were acquired in 20 subjects after obtaining written consent. A probabilistic air segmentation and sparse regression (PASSR) method was developed for pseudo CT estimation. Air segmentation was performed with assistance from a probabilistic air map. For nonair regions, the pseudo CT numbers were estimated via sparse regression by using atlas MR patches. The mean absolute percentage error (MAPE) on PET images was computed as the normalized mean absolute difference in PET signal intensity between a method and the reference standard continuous CT attenuation correction method. Friedman analysis of variance and Wilcoxon matched-pairs tests were performed for statistical comparison of MAPE between the PASSR method and Dixon segmentation, CT segmentation, and population averaged CT atlas (mean atlas) methods. Results The PASSR method yielded a mean MAPE ± standard deviation of 2.42% ± 1.0, 3.28% ± 0.93, and 2.16% ± 1.75, respectively, in the whole brain, gray matter, and white matter, which were significantly lower than the Dixon, CT segmentation, and mean atlas values (P < .01). Moreover, 68.0% ± 16.5, 85.8% ± 12.9, and 96.0% ± 2.5 of whole-brain volume had within ±2%, ±5%, and ±10% percentage error by using PASSR, respectively, which was significantly higher than other methods (P < .01). Conclusion PASSR outperformed the Dixon, CT segmentation, and mean atlas methods by reducing PET error owing to attenuation correction. © RSNA, 2014 PMID:25521778

64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer.

PubMed

Tamura, Kenji; Kurihara, Hiroaki; Yonemori, Kan; Tsuda, Hitoshi; Suzuki, Junko; Kono, Yuzuru; Honda, Natsuki; Kodaira, Makoto; Yamamoto, Harukaze; Yunokawa, Mayu; Shimizu, Chikako; Hasegawa, Koki; Kanayama, Yousuke; Nozaki, Satoshi; Kinoshita, Takayuki; Wada, Yasuhiro; Tazawa, Shusaku; Takahashi, Kazuhiro; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro

2013-11-01

The purpose of this study was to determine the safety, distribution, internal dosimetry, and initial human epidermal growth factor receptor 2 (HER2)-positive tumor images of (64)Cu-DOTA-trastuzumab in humans. PET was performed on 6 patients with primary or metastatic HER2-positive breast cancer at 1, 24, and 48 h after injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity data were collected from the blood, urine, and normal-tissue samples of these 6 patients, and the multiorgan biodistribution and internal dosimetry of the probe were evaluated. Safety data were collected for all the patients after the administration of (64)Cu-DOTA-trastuzumab and during the 1-wk follow-up period. According to our results, the best timing for the assessment of (64)Cu-DOTA-trastuzumab uptake by the tumor was 48 h after injection. Radiation exposure during (64)Cu-DOTA-trastuzumab PET was equivalent to that during conventional (18)F-FDG PET. The radioactivity in the blood was high, but uptake of (64)Cu-DOTA-trastuzumab in normal tissues was low. In 2 patients, (64)Cu-DOTA-trastuzumab PET showed brain metastases, indicative of blood-brain barrier disruptions. In 3 patients, (64)Cu-DOTA-trastuzumab PET imaging also revealed primary breast tumors at the lesion sites initially identified by CT. The findings of this study indicated that (64)Cu-DOTA-trastuzumab PET is feasible for the identification of HER2-positive lesions in patients with primary and metastatic breast cancer. The dosimetry and pharmacologic safety results were acceptable at the dose required for adequate PET imaging.

Monoamine oxidase: Radiotracer chemistry and human studies

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

Fowler, Joanna S.; Logan, Jean; Shumay, Elena

Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore » which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

Monoamine oxidase: Radiotracer chemistry and human studies

DOE PAGES

Fowler, Joanna S.; Logan, Jean; Shumay, Elena; ...

2015-03-01

Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore » which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

PubMed

Mielke, Michelle M; Hagen, Clinton E; Xu, Jing; Chai, Xiyun; Vemuri, Prashanthi; Lowe, Val J; Airey, David C; Knopman, David S; Roberts, Rosebud O; Machulda, Mary M; Jack, Clifford R; Petersen, Ronald C; Dage, Jeffrey L

2018-04-04

We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ. Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ. Copyright © 2018. Published by Elsevier Inc.

PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors

PubMed Central

Hall, Lance T; Titz, Benjamin; Robins, H Ian; Bednarz, Bryan P; Perlman, Scott B; Weichert, Jamey P; Kuo, John S

2017-01-01

CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with 124I for PET imaging, 131I for targeted radiotherapy and/or SPECT imaging, or 125I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of 124I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of 124I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. 124I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of 124I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. 124I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. 124I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has potential clinical relevance. Expansion of these studies is required to determine the clinical significance of the 124I-CLR1404 PET findings. PMID:28913154

Tau and Beta-Amyloid Deposition, Micro-Hemorrhage and Brain Function after Traumatic Brain Injury in War Veterans

DTIC Science & Technology

2016-10-01

tau PET imaging and 7T- MRI to the Australian Imaging Biomarkers and Lifestyle - Veterans study (AIBL-VETS) of post-traumatic stress disorder and...focal and widespread changes in white matter integrity. 4. 7T- MRI will reveal more extensive microhemorrhage than seen on 3T- MRI and this will relate...injury in war veterans. 6 | P a g e 1. Introduction The project will utilize tau, amyloid and FDG PET imaging, and MRI as well as clinical and

Performing Repeated Quantitative Small-Animal PET with an Arterial Input Function Is Routinely Feasible in Rats.

PubMed

Huang, Chi-Cheng; Wu, Chun-Hu; Huang, Ya-Yao; Tzen, Kai-Yuan; Chen, Szu-Fu; Tsai, Miao-Ling; Wu, Hsiao-Ming

2017-04-01

Performing quantitative small-animal PET with an arterial input function has been considered technically challenging. Here, we introduce a catheterization procedure that keeps a rat physiologically stable for 1.5 mo. We demonstrated the feasibility of quantitative small-animal 18 F-FDG PET in rats by performing it repeatedly to monitor the time course of variations in the cerebral metabolic rate of glucose (CMR glc ). Methods: Aseptic surgery was performed on 2 rats. Each rat underwent catheterization of the right femoral artery and left femoral vein. The catheters were sealed with microinjection ports and then implanted subcutaneously. Over the next 3 wk, each rat underwent 18 F-FDG quantitative small-animal PET 6 times. The CMR glc of each brain region was calculated using a 3-compartment model and an operational equation that included a k* 4 Results: On 6 mornings, we completed 12 18 F-FDG quantitative small-animal PET studies on 2 rats. The rats grew steadily before and after the 6 quantitative small-animal PET studies. The CMR glc of the conscious brain (e.g., right parietal region, 99.6 ± 10.2 μmol/100 g/min; n = 6) was comparable to that for 14 C-deoxyglucose autoradiographic methods. Conclusion: Maintaining good blood patency in catheterized rats is not difficult. Longitudinal quantitative small-animal PET imaging with an arterial input function can be performed routinely. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Development of a simultaneous optical/PET imaging system for awake mice

NASA Astrophysics Data System (ADS)

Takuwa, Hiroyuki; Ikoma, Yoko; Yoshida, Eiji; Tashima, Hideaki; Wakizaka, Hidekatsu; Shinaji, Tetsuya; Yamaya, Taiga

2016-09-01

Simultaneous measurements of multiple physiological parameters are essential for the study of brain disease mechanisms and the development of suitable therapies to treat them. In this study, we developed a measurement system for simultaneous optical imaging and PET for awake mice. The key elements of this system are the OpenPET, optical imaging and fixation apparatus for an awake mouse. The OpenPET is our original open-type PET geometry, which can be used in combination with another device because of the easily accessible open space of the former. A small prototype of the axial shift single-ring OpenPET was used. The objective lens for optical imaging with a mounted charge-coupled device camera was placed inside the open space of the AS-SROP. Our original fixation apparatus to hold an awake mouse was also applied. As a first application of this system, simultaneous measurements of cerebral blood flow (CBF) by laser speckle imaging (LSI) and [11C]raclopride-PET were performed under control and 5% CO2 inhalation (hypercapnia) conditions. Our system successfully obtained the CBF and [11C]raclopride radioactivity concentration simultaneously. Accumulation of [11C]raclopride was observed in the striatum where the density of dopamine D2 receptors is high. LSI measurements could be stably performed for more than 60 minutes. Increased CBF induced by hypercapnia was observed while CBF under the control condition was stable. We concluded that our imaging system should be useful for investigating the mechanisms of brain diseases in awake animal models.

Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease.

PubMed

Bandara, Nilantha; Sharma, Anuj K; Krieger, Stephanie; Schultz, Jason W; Han, Byung Hee; Rogers, Buck E; Mirica, Liviu M

2017-09-13

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11 C (20.4 min) and 18 F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64 Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described herein are a series of bifunctional chelators (BFCs), L 1 -L 5 , that were designed to tightly bind 64 Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD.

The serotonin-dopamine interaction measured with positron emission tomography (PET) and C-11 raclopride in normal human subjects

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

Smith, G.S.; Dewey, S.L.; Logan, J.

1994-05-01

Our previous studies have shown that the interaction between serotonin and dopamine can be measured with C-11 raclopride and PET in the baboon brain. A series of studies was undertaken to extend dim findings to the normal human brain. PET studies were conducted in male control subjects (n=8) using the CTI 931 tomograph. Two C-11 raclopride scans were performed, prior to and 180 minutes following administration of the selective serotonin releasing agent, fenfluramine (60mg/PO). The neuroendocrine response to fenfluramine challenge is commonly used in psychiatric research as an index of serotonin activity. The C-11 raclopride data were analyzed with themore » distribution volume method. For the group of subjects, an increase was observed in the striatum to cerebellum ratio (specific to non-specific binding ratio), in excess of the test-retest variability of the ligand. Variability in response was observed across subjects. These results are consistent with our previous findings in the baboon that citalopram administration increased C-11 raclopride binding, consistent with a decrease in endogenous dopamine. In vivo microdialysis studies in freely moving rats confirmed that citalopram produces a time-dependent decrease in extracellular dopamine levels, consistent with the PET results. In vivo PET studies of the serotonin-dopamine interaction are relevant to the evaluation of etiologic and therapeutic mechanisms in schizophrenia and affective disorder.« less

PET/MRI in cancer patients: first experiences and vision from Copenhagen.

PubMed

Kjær, Andreas; Loft, Annika; Law, Ian; Berthelsen, Anne Kiil; Borgwardt, Lise; Löfgren, Johan; Johnbeck, Camilla Bardram; Hansen, Adam Espe; Keller, Sune; Holm, Søren; Højgaard, Liselotte

2013-02-01

Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations.

PET/MRI for neurologic applications.

PubMed

Catana, Ciprian; Drzezga, Alexander; Heiss, Wolf-Dieter; Rosen, Bruce R

2012-12-01

PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation of the measured signals, creating opportunities impossible to realize using stand-alone instruments. This paper reviews the methodologic improvements and potential neurologic and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MRI data to improve the PET data quantification. On the MRI side, we present how improved PET quantification can be used to validate several MRI techniques. Finally, we describe promising research, translational, and clinical applications that can benefit from these advanced tools.

PET AND SPECT STUDIES IN CHILDREN WITH HEMISPHERIC LOW-GRADE GLIOMAS

PubMed Central

Juhász, Csaba; Bosnyák, Edit

2016-01-01

Molecular imaging is playing an increasing role in the pre-treatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting and improved detection of tumor recurrence. This review provides a brief overview of single photon emission computed tomography (SPECT) studies followed by a more detailed review of clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pre- and post-treatment evaluation of pediatric brain tumors. PMID:27659825

PET and SPECT studies in children with hemispheric low-grade gliomas.

PubMed

Juhász, Csaba; Bosnyák, Edit

2016-10-01

Molecular imaging is playing an increasing role in the pretreatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting, and improved detection of tumor recurrence. This review provides a brief overview of single-photon emission computed tomography (SPECT) studies followed by a more detailed review of the clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity, and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pretreatment and post-treatment evaluation of pediatric brain tumors.

Unique Distribution of Aromatase in the Human Brain: In Vivo Studies With PET and [N-Methyl-11C]Vorozole

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

Biegon, A.; Biegon, A.; Kim, S.W.

Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-{sup 11}C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-minmore » period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V{sub T}) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced VT in all regions, though the size of the reduction was region-dependent, ranging from {approx}70% blocking in thalamus andpreoptic area to {approx}10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.« less

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

Evaluation of D-isomers of 4-borono-2-18F-fluoro-phenylalanine and O-11C-methyl-tyrosine as brain tumor imaging agents: a comparative PET study with their L-isomers in rat brain glioma.

PubMed

Kanazawa, Masakatsu; Nishiyama, Shingo; Hashimoto, Fumio; Kakiuchi, Takeharu; Tsukada, Hideo

2018-06-13

The potential of the D-isomerization of 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) to improve its target tumor to non-target normal brain tissue ratio (TBR) was evaluated in rat brain glioma and compared with those of L- and D- 11 C-methyl-tyrosine ( 11 C-CMT). The L- or D-isomer of 18 F-FBPA was injected into rats through the tail vein, and their whole body kinetics and distributions were assessed using the tissue dissection method up to 90 min after the injection. The kinetics of L- and D- 18 F-FBPA or L- and D- 11 C-CMT in the C-6 glioma-inoculated rat brain were measured for 90 or 60 min, respectively, using high-resolution animal PET, and their TBRs were assessed. Tissue dissection analyses showed that D- 18 F-FBPA uptake was significantly lower than that of L- 18 F-FBPA in the brain and abdominal organs, except for the kidney and bladder, reflecting the faster elimination rate of D- 18 F-FBPA than L- 18 F-FBPA from the blood to the urinary tract. PET imaging using 18 F-FBPA revealed that although the brain uptake of D- 18 F-FBPA was significantly lower than that of L- 18 F-FBPA, the TBR of the D-isomer improved to 6.93 from 1.45 for the L-isomer. Similar results were obtained with PET imaging using 11 C-CMT with a smaller improvement in TBR to 1.75 for D- 11 C-CMT from 1.33 for L- 11 C-CMT. The present results indicate that D- 18 F-FBPA is a better brain tumor imaging agent with higher TBR than its original L-isomer and previously reported tyrosine-based PET imaging agents. This improved TBR of D- 18 F-FBPA without any pre-treatments, such as tentative blood-brain barrier disruption using hyperosmotic agents or sonication, suggests that the D-isomerization of BPA results in the more selective accumulation of 10 B in tumor cells that is more effective and less toxic than conventional L-BPA.

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

Correlation between direct microscopy and FDG-PET in the study of cerebral blood flow in rats

NASA Astrophysics Data System (ADS)

Blagosklonov, Oleg; Podoprigora, Guennady I.; Pushkin, Sergey V.; Nartsissov, Yaroslav R.; Comas, Laurent; Cardot, Jean-Claude; Boulahdour, Hatem

2007-07-01

Isotope studies provide valuable data about an organ's function in vivo. Thanks to positron emission tomography (PET) using the radiolabeled natural metabolites, such as [18F]-2-fluoro-deoxy-d-glucose (FDG), biological and physiological meaning of nuclear medicine scans has been considerably increased. Therefore it is of interest to elucidate the possibilities of the technique in a study of some natural metabolites like glycine influencing the blood microcirculation. Glycine, as a medicine, was recently shown to have a positive therapeutic effect in the treatment of patients with ischemic stroke and some other neurological disorders based on vascular disturbances. By previous direct biomicroscopic investigations of pial microvessels in laboratory rats an expressed vasodilatory effect of topically applied glycine was proved. The arterioles diameters depending on initial size have been increased by 200-250% for arterioles of 20-40 μm and by 150-200% for arterioles of 50-80 μm. The PET images were acquired before and after sublingual application of glycine (200 mg). The quantitative analysis of FDG volume concentration (Bq/ml) in the rat brain demonstrated that, in studies after glycine administration, maximal, minimal and mean FDG volume concentration in the brain increased by 200-250% in comparison with the baseline data. Thus, our results revealing evident correlation between FDG-PET images and direct biomicroscopic observations confirm the great potential of molecular imaging techniques to explore in vivo process in the brain.

[C-11]{beta}CNT: A new monoamine uptake ligand for studying serotonin and dopamine transporter sites in the living brain with PET

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

Mulholland, G.K.; Zheng, Q.H.; Zhou, F.C.

1996-05-01

There is considerable interest in measuring serotonin (5HT) and dopamine (DA) function in the human brain. Altered levels of 5HT and DA are recognized in drug abuse, neurotoxicities, psychiatric disorders, and neurodegenerative conditions including Alzheimer`s and Parkinson`s disease. Several phenyltropane analogs of cocaine bind tightly to both DA and 5HT uptake proteins. We have made a new agent from this class called {beta}CNT, 2{beta}-carboxymethyl-3{beta}-(2-naphthyl)-tropane, the isosteric O-for-CH{sub 2} analog of a compound reported to have among the highest measured affinities for DA and 5HT transporters and studied its in vivo brain distributions in animals for the first time. Optically puremore » {beta}CNT was made from cocaine, and labeled at the O-methyl position by esterification of {beta}CNT-acid with [C-11]CH{sub 3}OTfl under conditions similar to Wilson`s. HPLC-purified (99+%) final products (15-50% eob yield from CO{sub 2}, 40 min synth) had specific activities 0.1-1.2 Ci/{mu}mol at the time of injection. Preliminary [C-11]{beta}{beta}CNT rodent distribution showed very high brain uptake (3% ID at 60 min) and localization (striat: fr cort: hypo: cer: blood, 11: 5: 4: 1: 06). {beta}CNT-PET studies in juvenile pigs (5-20 mCi, 20-35 kg) found rapid brain uptake, and prominent retention (85 min) in midbrain, anterior brainstem and striatum, followed by cortex and olfactory bulb. Paroxetine pretreatment (5HT uptake blocker, 2mg/kg), diminished retention in most brain areas; nomifensine (DA/NE uptake blocker, 6 mg/kg) reduced striatum selectively. Direct comparisons of [C-11]{beta}CNT with other PET transporter radioligands {beta}CFT, {beta}CIT, and {beta}CTT (RTI-32) in the same pig found {beta}CNT had highest overall brain uptake among the agents. These initial results suggest {beta}CNT has favorable properties for imaging both 5HT and DA transporters in vivo, and further evaluation of its potential as a human PET agent is warranted.« less

Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET) System.

PubMed

Melroy, Samantha; Bauer, Christopher; McHugh, Matthew; Carden, Garret; Stolin, Alexander; Majewski, Stan; Brefczynski-Lewis, Julie; Wuest, Thorsten

2017-05-19

Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient's head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk-the Ambulatory Microdose PET (AM-PET)-is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities.

Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET) System

PubMed Central

Melroy, Samantha; Bauer, Christopher; McHugh, Matthew; Carden, Garret; Stolin, Alexander; Majewski, Stan; Brefczynski-Lewis, Julie; Wuest, Thorsten

2017-01-01

Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient’s head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk—the Ambulatory Microdose PET (AM-PET)—is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities. PMID:28534848

Design considerations for a C-shaped PET system, dedicated to small animal brain imaging, using GATE Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Efthimiou, N.; Papadimitroulas, P.; Kostou, T.; Loudos, G.

2015-09-01

Commercial clinical and preclinical PET scanners rely on the full cylindrical geometry for whole body scans as well as for dedicated organs. In this study we propose the construction of a low cost dual-head C-shaped PET system dedicated for small animal brain imaging. Monte Carlo simulation studies were performed using GATE toolkit to evaluate the optimum design in terms of sensitivity, distortions in the FOV and spatial resolution. The PET model is based on SiPMs and BGO pixelated arrays. Four different configurations with C- angle 0°, 15°, 30° and 45° within the modules, were considered. Geometrical phantoms were used for the evaluation process. STIR software, extended by an efficient multi-threaded ray tracing technique, was used for the image reconstruction. The algorithm automatically adjusts the size of the FOV according to the shape of the detector's geometry. The results showed improvement in sensitivity of ∼15% in case of 45° C-angle compared to the 0° case. The spatial resolution was found 2 mm for 45° C-angle.

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

Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET.

PubMed

Bankstahl, Jens P; Kuntner, Claudia; Abrahim, Aiman; Karch, Rudolf; Stanek, Johann; Wanek, Thomas; Wadsak, Wolfgang; Kletter, Kurt; Müller, Markus; Löscher, Wolfgang; Langer, Oliver

2008-08-01

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB.

Effect of MRI Acoustic Noise on Cerebral FDG Uptake in Simultaneous MR-PET Imaging

PubMed Central

Abolmaali, Nasreddin; Arabasz, Grae; Guimaraes, Alexander R.; Catana, Ciprian

2013-01-01

Integrated scanners capable of simultaneous PET and MRI data acquisition are now available for human use. Although the scanners’ manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the two modalities, the potential physiological inference has not been evaluated. In this work, we have studied the influence of the acoustic noise produced by the MR gradients on brain FDG uptake in the Siemens MR-BrainPET prototype. While particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. Methods The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, ten healthy volunteers underwent two simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a “quiet” (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a “noisy” (test) case in which MR sequences were run for the entire time. Cortical and subcortical regions of interest (ROIs) were derived from the high-resolution morphological MR data using FreeSurfer. The changes in FDG uptake in the FreeSurfer-derived ROIs between the two conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. Results Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The ROI-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13±4.73%) and static (4.18±2.87%) images. SPM8 analysis showed no statistically significant clusters in any images when a p<0.05 (corrected) was used; however, a p<0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left: 8.37±1.55%, right: 8.20±1.17%), but only unilateral increase in the static image (left: 8.68±3.89%). Conclusion Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation related) changes in FDG uptake in this region, if the expected effects are of comparable amplitude. PMID:23462677

Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis.

PubMed

Solnes, Lilja B; Jones, Krystyna M; Rowe, Steven P; Pattanayak, Puskar; Nalluri, Abhinav; Venkatesan, Arun; Probasco, John C; Javadi, Mehrbod S

2017-08-01

Diagnosis of autoimmune encephalitis presents some challenges in the clinical setting because of varied clinical presentations and delay in obtaining antibody panel results. We examined the role of neuroimaging in the setting of autoimmune encephalitides, comparing the utility of 18 F-FDG PET/CT versus conventional brain imaging with MRI. Methods: A retrospective study was performed assessing the positivity rate of MRI versus 18 F-FDG PET/CT during the initial workup of 23 patients proven to have antibody-positive autoimmune encephalitis. 18 F-FDG PET/CT studies were analyzed both qualitatively and semiquantitatively. Areas of cortical lobar hypo (hyper)-metabolism in the cerebrum that were 2 SDx from the mean were recorded as abnormal. Results: On visual inspection, all patients were identified as having an abnormal pattern of 18 F-FDG uptake. In semiquantitative analysis, at least 1 region of interest with metabolic change was identified in 22 of 23 (95.6%) patients using a discriminating z score of 2. Overall, 18 F-FDG PET/CT was more often abnormal during the diagnostic period than MRI (10/23, 43% of patients). The predominant finding on brain 18 F-FDG PET/CT imaging was lobar hypometabolism, being observed in 21 of 23 (91.3%) patients. Hypometabolism was most commonly observed in the parietal lobe followed by the occipital lobe. An entire subset of antibody-positive patients, anti- N -methyl-d-aspartate receptor (5 patients), had normal MRI results and abnormal 18 F-FDG PET/CT findings whereas the other subsets demonstrated a greater heterogeneity. Conclusion: Brain 18 F-FDG PET/CT may play a significant role in the initial evaluation of patients with clinically suspected antibody-mediated autoimmune encephalitis. Given that it is more often abnormal when compared with MRI in the acute setting, this molecular imaging technique may be better positioned as an early biomarker of disease so that treatment may be initiated earlier, resulting in improved patient outcomes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Free-running ADC- and FPGA-based signal processing method for brain PET using GAPD arrays

NASA Astrophysics Data System (ADS)

Hu, Wei; Choi, Yong; Hong, Key Jo; Kang, Jihoon; Jung, Jin Ho; Huh, Youn Suk; Lim, Hyun Keong; Kim, Sang Su; Kim, Byung-Tae; Chung, Yonghyun

2012-02-01

Currently, for most photomultiplier tube (PMT)-based PET systems, constant fraction discriminators (CFD) and time to digital converters (TDC) have been employed to detect gamma ray signal arrival time, whereas anger logic circuits and peak detection analog-to-digital converters (ADCs) have been implemented to acquire position and energy information of detected events. As compared to PMT the Geiger-mode avalanche photodiodes (GAPDs) have a variety of advantages, such as compactness, low bias voltage requirement and MRI compatibility. Furthermore, the individual read-out method using a GAPD array coupled 1:1 with an array scintillator can provide better image uniformity than can be achieved using PMT and anger logic circuits. Recently, a brain PET using 72 GAPD arrays (4×4 array, pixel size: 3 mm×3 mm) coupled 1:1 with LYSO scintillators (4×4 array, pixel size: 3 mm×3 mm×20 mm) has been developed for simultaneous PET/MRI imaging in our laboratory. Eighteen 64:1 position decoder circuits (PDCs) were used to reduce GAPD channel number and three off-the-shelf free-running ADC and field programmable gate array (FPGA) combined data acquisition (DAQ) cards were used for data acquisition and processing. In this study, a free-running ADC- and FPGA-based signal processing method was developed for the detection of gamma ray signal arrival time, energy and position information all together for each GAPD channel. For the method developed herein, three DAQ cards continuously acquired 18 channels of pre-amplified analog gamma ray signals and 108-bit digital addresses from 18 PDCs. In the FPGA, the digitized gamma ray pulses and digital addresses were processed to generate data packages containing pulse arrival time, baseline value, energy value and GAPD channel ID. Finally, these data packages were saved to a 128 Mbyte on-board synchronous dynamic random access memory (SDRAM) and then transferred to a host computer for coincidence sorting and image reconstruction. In order to evaluate the functionality of the developed signal processing method, energy and timing resolutions for brain PET were measured via the placement of a 6 μCi 22Na point source at the center of the PET scanner. Furthermore the PET image of the hot rod phantom (rod diameter: from 2.5 mm to 6.5 mm) with activity of 1 mCi was simulated, and then image acquisition experiment was performed using the brain PET. Measured average energy resolution for 1152 GAPD channels and system timing resolution were 19.5% (FWHM%) and 2.7 ns (FWHM), respectively. With regard to the acquisition of the hot rod phantom image, rods could be resolved down to a diameter of 2.5 mm, which was similar to simulated results. The experimental results demonstrated that the signal processing method developed herein was successfully implemented for brain PET. This reduced the complexity, cost and developing duration for PET system relative to normal PET electronics, and it will obviously be useful for the development of high-performance investigational PET systems.

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

PubMed

Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-09-21

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units ([Formula: see text]) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into [Formula: see text] was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of [Formula: see text] corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

NASA Astrophysics Data System (ADS)

Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

2017-10-01

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units (HU ) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into HU was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of 4~mm corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

Decreased occipital lobe metabolism by FDG-PET/CT

PubMed Central

Solnes, Lilja; Nalluri, Abhinav; Cohen, Jesse; Jones, Krystyna M.; Zan, Elcin; Javadi, Mehrbod S.; Venkatesan, Arun

2017-01-01

Objective: To compare brain metabolism patterns on fluorodeoxyglucose (FDG)-PET/CT in anti–NMDA receptor and other definite autoimmune encephalitis (AE) and to assess how these patterns differ between anti–NMDA receptor neurologic disability groups. Methods: Retrospective review of clinical data and initial dedicated brain FDG-PET/CT studies for neurology inpatients with definite AE, per published consensus criteria, treated at a single academic medical center over a 10-year period. Z-score maps of FDG-PET/CT were made using 3-dimensional stereotactic surface projections in comparison to age group–matched controls. Brain region mean Z scores with magnitudes ≥2.00 were interpreted as significant. Comparisons were made between anti–NMDA receptor and other definite AE patients as well as among patients with anti–NMDA receptor based on modified Rankin Scale (mRS) scores at the time of FDG-PET/CT. Results: The medial occipital lobes were markedly hypometabolic in 6 of 8 patients with anti–NMDA receptor encephalitis and as a group (Z = −4.02, interquartile range [IQR] 2.14) relative to those with definite AE (Z = −2.32, 1.46; p = 0.004). Among patients with anti–NMDA receptor encephalitis, the lateral and medial occipital lobes were markedly hypometabolic for patients with mRS 4–5 (lateral occipital lobe Z = −3.69, IQR 1; medial occipital lobe Z = −4.08, 1) compared with those with mRS 0–3 (lateral occipital lobe Z = −0.83, 2; p < 0.0005; medial occipital lobe Z = −1.07, 2; p = 0.001). Conclusions: Marked medial occipital lobe hypometabolism by dedicated brain FDG-PET/CT may serve as an early biomarker for discriminating anti–NMDA receptor encephalitis from other AE. Resolution of lateral and medial occipital hypometabolism may correlate with improved neurologic status in anti–NMDA receptor encephalitis. PMID:29159205

Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [(18)F]-Florbetaben PET Quantitation in Alzheimer's Model Mice.

PubMed

Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

2016-01-01

Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [(18)F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (R mean = 0.75) was slightly superior to the brainstem (R mean = 0.74) and the cerebellum (R mean = 0.73). Automated brain normalization with reference region templates presents an excellent method to avoid the inter-reader variability in preclinical Aβ-PET scans. Intracerebral reference regions lacking Aβ pathology serve for precise longitudinal in vivo quantification of [(18)F]-florbetaben PET. Hindbrain white matter reference performed best when considering the composite of quality criteria.

Evaluation of an attenuation correction method for PET/MR imaging of the head based on substitute CT images.

PubMed

Larsson, Anne; Johansson, Adam; Axelsson, Jan; Nyholm, Tufve; Asklund, Thomas; Riklund, Katrine; Karlsson, Mikael

2013-02-01

The aim of this study was to evaluate MR-based attenuation correction of PET emission data of the head, based on a previously described technique that calculates substitute CT (sCT) images from a set of MR images. Images from eight patients, examined with (18)F-FLT PET/CT and MRI, were included. sCT images were calculated and co-registered to the corresponding CT images, and transferred to the PET/CT scanner for reconstruction. The new reconstructions were then compared with the originals. The effect of replacing bone with soft tissue in the sCT-images was also evaluated. The average relative difference between the sCT-corrected PET images and the CT-corrected PET images was 1.6% for the head and 1.9% for the brain. The average standard deviations of the relative differences within the head were relatively high, at 13.2%, primarily because of large differences in the nasal septa region. For the brain, the average standard deviation was lower, 4.1%. The global average difference in the head when replacing bone with soft tissue was 11%. The method presented here has a high rate of accuracy, but high-precision quantitative imaging of the nasal septa region is not possible at the moment.

PET/MRI for Neurological Applications

PubMed Central

Catana, Ciprian; Drzezga, Alexander; Heiss, Wolf-Dieter; Rosen, Bruce R.

2013-01-01

PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MR data acquisition allows the spatial and temporal correlation of the measured signals, opening up opportunities impossible to realize using stand-alone instruments. This paper reviews the methodological improvements and potential neurological and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MR data to improve the PET data quantification. On the MR side, we present how improved PET quantification could be used to validate a number of MR techniques. Finally, we describe promising research, translational and clinical applications that could benefit from these advanced tools. PMID:23143086

Longitudinal tau PET in ageing and Alzheimer’s disease

PubMed Central

Jack, Clifford R; Wiste, Heather J; Schwarz, Christopher G; Lowe, Val J; Senjem, Matthew L; Vemuri, Prashanthi; Weigand, Stephen D; Therneau, Terry M; Knopman, Dave S; Gunter, Jeffrey L; Jones, David T; Graff-Radford, Jonathan; Kantarci, Kejal; Roberts, Rosebud O; Mielke, Michelle M; Machulda, Mary M; Petersen, Ronald C

2018-01-01

Abstract See Hansson and Mormino (doi:10.1093/brain/awy065) for a scientific commentary on this article. Our objective was to compare different whole-brain and region-specific measurements of within-person change on serial tau PET and evaluate its utility for clinical trials. We studied 126 individuals: 59 cognitively unimpaired with normal amyloid, 37 cognitively unimpaired with abnormal amyloid, and 30 cognitively impaired with an amnestic phenotype and abnormal amyloid. All had baseline amyloid PET and two tau PET, MRI, and clinical assessments. We compared the topography across all cortical regions of interest of tau PET accumulation rates and the rates of four different whole-brain or region-specific meta-regions of interest among the three clinical groups. We computed sample size estimates for change in tau PET, cortical volume, and memory/mental status indices for use as outcome measures in clinical trials. The cognitively unimpaired normal amyloid group had no observable tau accumulation throughout the brain. Tau accumulation rates in cognitively unimpaired abnormal amyloid were low [0.006 standardized uptake value ratio (SUVR), 0.5%, per year] but greater than rates in the cognitively unimpaired normal amyloid group in the basal and mid-temporal, retrosplenial, posterior cingulate, and entorhinal regions of interest. Thus, the earliest elevation in accumulation rates was widespread and not confined to the entorhinal cortex. Tau accumulation rates in the cognitively impaired abnormal amyloid group were 0.053 SUVR (3%) per year and greater than rates in cognitively unimpaired abnormal amyloid in all cortical areas except medial temporal. Rates of accumulation in the four meta-regions of interest differed but only slightly from one another. Among all tau PET meta-regions of interest, sample size estimates were smallest for a temporal lobe composite within cognitively unimpaired abnormal amyloid and for the late Alzheimer’s disease meta-region of interest within cognitively impaired abnormal amyloid. The ordering of the sample size estimates by outcome measure was MRI < tau PET < cognitive measures. At a group-wise level, observable rates of short-term serial tau accumulation were only seen in the presence of abnormal amyloid. As disease progressed to clinically symptomatic stages (cognitively impaired abnormal amyloid), observable rates of tau accumulation were seen uniformly throughout the brain providing evidence that tau does not accumulate in one area at a time or in start-stop, stepwise sequence. The information captured by rate measures in different meta-regions of interest, even those with little topographic overlap, was similar. The implication is that rate measurements from simple meta-regions of interest, without the need for Braak-like staging, may be sufficient to capture progressive within-person accumulation of pathologic tau. Tau PET SUVR measures should be an efficient outcome measure in disease-modifying clinical trials. PMID:29538647

Evaluation of the co-registration capabilities of a MRI/PET compatible bed in an Experimental autoimmune encephalomyelitis (EAE) model

NASA Astrophysics Data System (ADS)

Esposito, Giovanna; D'angeli, Luca; Bartoli, Antonietta; Chaabane, Linda; Terreno, Enzo

2013-02-01

Positron Emission Tomography (PET) with 18F-FDG is a promising tool for the detection and evaluation of active inflammation in animal models of neuroinflammation. MRI is a complementary imaging technique with high resolution and contrast suitable to obtain the anatomical data required to analyze PET data. To combine PET and MRI modalities, we developed a support bed system compatible for both scanners that allowed to perform imaging exams without animal repositioning. With this approach, MRI and PET data were acquired in mice with Experimental autoimmune encephalomyelitis (EAE). In this model, it was possible to measure a variation of 18F-FDG uptake proportional to the degree of disease severity which is mainly related to Central Nervous System (CNS) inflammation. Against the low resolved PET images, the co-registered MRI/PET images allowed to distinguish the different brain structures and to obtain a more accurate tracer evaluation. This is essential in particular for brain regions whose size is of the order of the spatial resolution of PET.

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

PubMed

Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

2017-08-01

The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [ P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion: 18 F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Quantitative analysis of MRI-guided attenuation correction techniques in time-of-flight brain PET/MRI.

PubMed

Mehranian, Abolfazl; Arabi, Hossein; Zaidi, Habib

2016-04-15

In quantitative PET/MR imaging, attenuation correction (AC) of PET data is markedly challenged by the need of deriving accurate attenuation maps from MR images. A number of strategies have been developed for MRI-guided attenuation correction with different degrees of success. In this work, we compare the quantitative performance of three generic AC methods, including standard 3-class MR segmentation-based, advanced atlas-registration-based and emission-based approaches in the context of brain time-of-flight (TOF) PET/MRI. Fourteen patients referred for diagnostic MRI and (18)F-FDG PET/CT brain scans were included in this comparative study. For each study, PET images were reconstructed using four different attenuation maps derived from CT-based AC (CTAC) serving as reference, standard 3-class MR-segmentation, atlas-registration and emission-based AC methods. To generate 3-class attenuation maps, T1-weighted MRI images were segmented into background air, fat and soft-tissue classes followed by assignment of constant linear attenuation coefficients of 0, 0.0864 and 0.0975 cm(-1) to each class, respectively. A robust atlas-registration based AC method was developed for pseudo-CT generation using local weighted fusion of atlases based on their morphological similarity to target MR images. Our recently proposed MRI-guided maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm was employed to estimate the attenuation map from TOF emission data. The performance of the different AC algorithms in terms of prediction of bones and quantification of PET tracer uptake was objectively evaluated with respect to reference CTAC maps and CTAC-PET images. Qualitative evaluation showed that the MLAA-AC method could sparsely estimate bones and accurately differentiate them from air cavities. It was found that the atlas-AC method can accurately predict bones with variable errors in defining air cavities. Quantitative assessment of bone extraction accuracy based on Dice similarity coefficient (DSC) showed that MLAA-AC and atlas-AC resulted in DSC mean values of 0.79 and 0.92, respectively, in all patients. The MLAA-AC and atlas-AC methods predicted mean linear attenuation coefficients of 0.107 and 0.134 cm(-1), respectively, for the skull compared to reference CTAC mean value of 0.138cm(-1). The evaluation of the relative change in tracer uptake within 32 distinct regions of the brain with respect to CTAC PET images showed that the 3-class MRAC, MLAA-AC and atlas-AC methods resulted in quantification errors of -16.2 ± 3.6%, -13.3 ± 3.3% and 1.0 ± 3.4%, respectively. Linear regression and Bland-Altman concordance plots showed that both 3-class MRAC and MLAA-AC methods result in a significant systematic bias in PET tracer uptake, while the atlas-AC method results in a negligible bias. The standard 3-class MRAC method significantly underestimated cerebral PET tracer uptake. While current state-of-the-art MLAA-AC methods look promising, they were unable to noticeably reduce quantification errors in the context of brain imaging. Conversely, the proposed atlas-AC method provided the most accurate attenuation maps, and thus the lowest quantification bias. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

PubMed Central

Schreiner, Simon J.; Liu, Xinyang; Gietl, Anton F.; Wyss, Michael; Steininger, Stefanie C.; Gruber, Esmeralda; Treyer, Valerie; Meier, Irene B.; Kälin, Andrea M.; Leh, Sandra E.; Buck, Alfred; Nitsch, Roger M.; Pruessmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD. PMID:25249977

The effect of 18F-FDG-PET image reconstruction algorithms on the expression of characteristic metabolic brain network in Parkinson's disease.

PubMed

Tomše, Petra; Jensterle, Luka; Rep, Sebastijan; Grmek, Marko; Zaletel, Katja; Eidelberg, David; Dhawan, Vijay; Ma, Yilong; Trošt, Maja

2017-09-01

To evaluate the reproducibility of the expression of Parkinson's Disease Related Pattern (PDRP) across multiple sets of 18F-FDG-PET brain images reconstructed with different reconstruction algorithms. 18F-FDG-PET brain imaging was performed in two independent cohorts of Parkinson's disease (PD) patients and normal controls (NC). Slovenian cohort (20 PD patients, 20 NC) was scanned with Siemens Biograph mCT camera and reconstructed using FBP, FBP+TOF, OSEM, OSEM+TOF, OSEM+PSF and OSEM+PSF+TOF. American Cohort (20 PD patients, 7 NC) was scanned with GE Advance camera and reconstructed using 3DRP, FORE-FBP and FORE-Iterative. Expressions of two previously-validated PDRP patterns (PDRP-Slovenia and PDRP-USA) were calculated. We compared the ability of PDRP to discriminate PD patients from NC, differences and correlation between the corresponding subject scores and ROC analysis results across the different reconstruction algorithms. The expression of PDRP-Slovenia and PDRP-USA networks was significantly elevated in PD patients compared to NC (p<0.0001), regardless of reconstruction algorithms. PDRP expression strongly correlated between all studied algorithms and the reference algorithm (r⩾0.993, p<0.0001). Average differences in the PDRP expression among different algorithms varied within 0.73 and 0.08 of the reference value for PDRP-Slovenia and PDRP-USA, respectively. ROC analysis confirmed high similarity in sensitivity, specificity and AUC among all studied reconstruction algorithms. These results show that the expression of PDRP is reproducible across a variety of reconstruction algorithms of 18F-FDG-PET brain images. PDRP is capable of providing a robust metabolic biomarker of PD for multicenter 18F-FDG-PET images acquired in the context of differential diagnosis or clinical trials. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Brain Correlates of Stuttering and Syllable Production: Gender Comparison and Replication.

ERIC Educational Resources Information Center

Ingham, Roger J.; Fox, Peter T.; Ingham, Janis C.; Xiong, Jinhu; Zamarripa, Frank; Hardies, L. Jean; Lancaster, Jack L.

2004-01-01

This article reports a gender replication study of the P. T. Fox et a. (2000) performance correlation analysis of neural systems that distinguish between normal and stuttered speech in adult males. Positron-emission tomographic (PET) images of cerebral blood flow (CBF) were correlated with speech behavior scores obtained during PET imaging for 10…

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

PubMed

Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

2017-01-04

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis, transport, and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders. Copyright © 2017 the authors 0270-6474/17/370120-09$15.00/0.

FDG-PET and Neuropsychiatric Symptoms among Cognitively Normal Elderly Persons: The Mayo Clinic Study of Aging.

PubMed

Krell-Roesch, Janina; Ruider, Hanna; Lowe, Val J; Stokin, Gorazd B; Pink, Anna; Roberts, Rosebud O; Mielke, Michelle M; Knopman, David S; Christianson, Teresa J; Machulda, Mary M; Jack, Clifford R; Petersen, Ronald C; Geda, Yonas E

2016-07-14

One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer's disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged > 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23-3.64); the point estimate was further elevated for APOE ɛ4 carriers (OR = 2.59; 1.00-6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD.

Modifiable Risk Factors and Brain PET Measures of Amyloid and Tau in Non-Demented Adults with Memory Complaints

PubMed Central

Merrill, David A.; Siddarth, Prabha; Raji, Cyrus A.; Emerson, Natacha D.; Rueda, Florangel; Ercoli, Linda M.; Miller, Karen J.; Lavretsky, Helen; Harris, Laurel M.; Burggren, Alison C.; Bookheimer, Susan Y.; Barrio, Jorge R.; Small, Gary W.

2016-01-01

Objective Exercise and diet impact body composition, but their age-related brain effects are unclear at the molecular imaging level. To address these issues, we determined whether body mass index (BMI), physical activity, and diet relate to brain positron emission tomography (PET) of amyloid plaques and tau tangles using 2-(1-(6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP). Methods Volunteers (n = 44, mean age = 62.6 ± 10.7 years) with subjective memory impairment (n = 24) or mild cognitive impairment (MCI; n = 20) were recruited by soliciting for memory complaints. Levels of physical activity and extent of following a Mediterranean-type diet were self-reported. FDDNP-PET scans assessed plaque/tangle binding in Alzheimer’s disease (AD)-associated regions (frontal, parietal, medial and lateral temporal, posterior cingulate). Mixed models controlling for known covariates examined BMI, physical activity, and diet in relation to FDDNP-PET. Results MCI subjects with above normal BMI (>25) had higher FDDNP-PET binding compared to those with normal BMI (1.11(.03) vs 1.08(.03), ES=1.04, t(35)=3.3, p=.002). Greater physical activity was associated with lower FDDNP-PET binding in MCI subjects (1.07(.03) vs 1.11(.03), ES=1.13, t(35) =−3.1, p=.004) but not in subjects with subjective memory impairment (1.07 (.03) vs 1.07(.03), ES=.02, t(35)=−0.1, p=.9). Healthier diet related to lower FDDNP-PET binding, regardless of cognitive status (1.07(.03) vs 1.09(.02), ES=0.72, t(35)=−2.1, p = .04). Conclusion and Relevance These preliminary findings are consistent with a relationship between risk modifiers and brain plaque/tangle deposition in non-demented individuals and supports maintenance of normal body weight, regular physical activity, and healthy diet adherence to protect the brain during aging. PMID:27421618

Using CT Data to Improve the Quantitative Analysis of 18F-FBB PET Neuroimages

PubMed Central

Segovia, Fermín; Sánchez-Vañó, Raquel; Górriz, Juan M.; Ramírez, Javier; Sopena-Novales, Pablo; Testart Dardel, Nathalie; Rodríguez-Fernández, Antonio; Gómez-Río, Manuel

2018-01-01

18F-FBB PET is a neuroimaging modality that is been increasingly used to assess brain amyloid deposits in potential patients with Alzheimer's disease (AD). In this work, we analyze the usefulness of these data to distinguish between AD and non-AD patients. A dataset with 18F-FBB PET brain images from 94 subjects diagnosed with AD and other disorders was evaluated by means of multiple analyses based on t-test, ANOVA, Fisher Discriminant Analysis and Support Vector Machine (SVM) classification. In addition, we propose to calculate amyloid standardized uptake values (SUVs) using only gray-matter voxels, which can be estimated using Computed Tomography (CT) images. This approach allows assessing potential brain amyloid deposits along with the gray matter loss and takes advantage of the structural information provided by most of the scanners used for PET examination, which allow simultaneous PET and CT data acquisition. The results obtained in this work suggest that SUVs calculated according to the proposed method allow AD and non-AD subjects to be more accurately differentiated than using SUVs calculated with standard approaches. PMID:29930505

Positron emission tomography scans obtained for the evaluation of cognitive dysfunction.

PubMed

Silverman, Daniel H S; Mosconi, Lisa; Ercoli, Linda; Chen, Wei; Small, Gary W

2008-07-01

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with (18)F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with (18)F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.

PubMed

Chen, Wei; Cloughesy, Timothy; Kamdar, Nirav; Satyamurthy, Nagichettiar; Bergsneider, Marvin; Liau, Linda; Mischel, Paul; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

2005-06-01

3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0.0005 and P = 0.001, respectively). Thirty-minute (18)F-FLT PET 5 min after injection was more sensitive than (18)F-FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, (18)F-FLT appears to be a promising tracer as a surrogate marker of proliferation in high-grade gliomas.

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.

Inhibition of [11C]mirtazapine binding by alpha2-adrenoceptor antagonists studied by positron emission tomography in living porcine brain.

PubMed

Smith, Donald F; Dyve, Suzan; Minuzzi, Luciano; Jakobsen, Steen; Munk, Ole L; Marthi, Katalin; Cumming, Paul

2006-06-15

We have developed [(11)C]mirtazapine as a ligand for PET studies of antidepressant binding in living brain. However, previous studies have determined neither optimal methods for quantification of [(11)C]mirtazapine binding nor the pharmacological identity of this binding. To obtain that information, we have now mapped the distribution volume (V(d)) of [(11)C]mirtazapine relative to the arterial input in the brain of three pigs, in a baseline condition and after pretreatment with excess cold mirtazapine (3 mg/kg). Baseline V(d) ranged from 6 ml/ml in cerebellum to 18 ml/ml in frontal cortex, with some evidence for a small self-displaceable binding component in the cerebellum. Regional binding potentials (pBs) obtained by a constrained two-compartment model, using the V(d) observation in cerebellum, were consistently higher than pBs obtained by other arterial input or reference tissue methods. We found that adequate quantification of pB was obtained using the simplified reference tissue method. Concomitant PET studies with [(15)O]-water indicated that mirtazapine challenge increased CBF uniformly in cerebellum and other brain regions, supporting the use of this reference tissue for calculation of [(11)C]mirtazapine pB. Displacement by mirtazapine was complete in the cerebral cortex, but only 50% in diencephalon, suggesting the presence of multiple binding sites of differing affinities in that tissue. Competition studies with yohimbine and RX 821002 showed decreases in [(11)C]mirtazapine pB throughout the forebrain; use of the multireceptor version of the Michaelis-Menten equation indicated that 42% of [(11)C]mirtazapine binding in cortical regions is displaceable by yohimbine. Thus, PET studies confirm that [(11)C]mirtazapine affects alpha(2)-adrenoceptor binding sites in living brain. (c) 2006 Wiley-Liss, Inc.

A Study of the Focal Adhesion Kinase Inhibitor GSK2256098 in Patients with Recurrent Glioblastoma with Evaluation of Tumor Penetration of [11C]GSK2256098.

PubMed

Brown, Nicholas F; Williams, Matthew; Arkenau, Hendrik-Tobias; Fleming, Ronald A; Tolson, Jerry; Yan, Li; Zhang, Jianping; Swartz, Lisa; Singh, Rajendra; Auger, Kurt R; Lenox, Laurie; Cox, David; Lewis, Yvonne; Plisson, Christophe; Searle, Graham; Saleem, Azeem; Blagden, Sarah; Mulholland, Paul

2018-05-17

GSK2256098 is a novel oral focal adhesion kinase inhibitor. Preclinical studies demonstrate growth inhibition in glioblastoma cell lines. However, rodent studies indicate limited blood-brain barrier penetration. In this expansion cohort within a phase I study, the safety, tolerability, pharmacokinetics and clinical activity of GSK2256098 were evaluated in patients with recurrent glioblastoma. Biodistribution and kinetics of [11C]GSK2256098 were assessed in a sub-study using positron-emission tomography (PET). Patients were treated with GSK2256098 until disease progression or withdrawal due to adverse events (AEs). Serial pharmacokinetic samples were collected on Day 1. On a single day between Days 9-20, patients received a microdose of intravenous [11C]GSK2256098 and scanned with PET over 90 minutes with parallel PK sample collection. Response was assessed by MRI every six weeks. Thirteen patients were treated in three dose cohorts (1000 mg, 750 mg, 500 mg; all dosed twice-daily). The maximum tolerated dose was 1000 mg twice-daily. Dose-limiting toxicities were related to cerebral edema. Treatment-related AEs (>25%) were diarrhea, fatigue and nausea. Eight patients participated in the PET sub-study, with [11C]GSK2256098 VT estimates of 0.9 in tumor tissue, 0.5 in surrounding T2 enhancing areas, and 0.4 in normal brain,. Best response of stable disease was observed in three patients, including one patient on treatment for 11.3 months. GSK2256098 was tolerable in patients with relapsed glioblastoma. GSK2256098 crossed the blood-brain barrier at low levels into normal brain, but at markedly higher levels into tumor, consistent with tumor-associated blood-brain barrier disruption. Additional clinical trials of GSK2256098 are ongoing.

Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.

PubMed

Berti, Valentina; Walters, Michelle; Sterling, Joanna; Quinn, Crystal G; Logue, Michelle; Andrews, Randolph; Matthews, Dawn C; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Mosconi, Lisa

2018-05-15

To examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain β-amyloid load via 11 C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18 F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife. Seventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally. MeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions ( p < 0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group ( p interaction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD. Lower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD. © 2018 American Academy of Neurology.

Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688.

PubMed

Ametamey, Simon M; Treyer, Valerie; Streffer, Johannes; Wyss, Matthias T; Schmidt, Mark; Blagoev, Milen; Hintermann, Samuel; Auberson, Yves; Gasparini, Fabrizio; Fischer, Uta C; Buck, Alfred

2007-02-01

3-(6-Methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime (11C-ABP688), a noncompetitive and highly selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET agent. Six healthy male volunteers (mean age, 25 y; range, 21-33 y) were studied. Brain perfusion (15O-H2O) was measured immediately before each 11C-ABP688 PET scan. For anatomic coregistration, T1-weighted MRI was performed on each subject. Arterial blood samples for the determination of the arterial input curve were obtained at predefined time points, and 11C-ABP688 uptake was assessed quantitatively using a 2-tissue-compartment model. An initial rapid uptake of radioactivity followed by a gradual clearance from all examined brain regions was observed. Relatively high radioactivity concentrations were observed in mGluR5-rich brain regions such as the anterior cingulate, medial temporal lobe, amygdala, caudate, and putamen, whereas radioactivity uptake in the cerebellum and white matter, regions known to contain low densities of mGluR5, was low. Specific distribution volume as an outcome measure of mGluR5 density in the various brain regions ranged from 5.45 +/- 1.47 (anterior cingulate) to 1.91 +/- 0.32 (cerebellum), and the rank order of the corresponding specific distribution volumes of 11C-ABP688 in cortical regions was temporal > frontal > occipital > parietal. The metabolism of 11C-ABP688 in plasma was rapid; at 60 min after injection, 25% +/- 0.03% of radioactivity measured in the plasma of healthy volunteers was intact parent compound. The results of these studies indicate that 11C-ABP688 has suitable characteristics and is a promising PET ligand for imaging mGluR5 distribution in humans. Furthermore, it could be of great value for the selection of appropriate doses of clinically relevant candidate drugs that bind to mGluR5 and for PET studies of patients with psychiatric and neurologic disorders.

PET Imaging - from Physics to Clinical Molecular Imaging

NASA Astrophysics Data System (ADS)

Majewski, Stan

2008-03-01

From the beginnings many years ago in a few physics laboratories and first applications as a research brain function imager, PET became lately a leading molecular imaging modality used in diagnosis, staging and therapy monitoring of cancer, as well as has increased use in assessment of brain function (early diagnosis of Alzheimer's, etc) and in cardiac function. To assist with anatomic structure map and with absorption correction CT is often used with PET in a duo system. Growing interest in the last 5-10 years in dedicated organ specific PET imagers (breast, prostate, brain, etc) presents again an opportunity to the particle physics instrumentation community to contribute to the important field of medical imaging. In addition to the bulky standard ring structures, compact, economical and high performance mobile imagers are being proposed and build. The latest development in standard PET imaging is introduction of the well known TOF concept enabling clearer tomographic pictures of the patient organs. Development and availability of novel photodetectors such as Silicon PMT immune to magnetic fields offers an exciting opportunity to use PET in conjunction with MRI and fMRI. As before with avalanche photodiodes, particle physics community plays a leading role in developing these devices. The presentation will mostly focus on present and future opportunities for better PET designs based on new technologies and methods: new scintillators, photodetectors, readout, software.

Thinking about the Brain to Balance Classroom Literacy Programs

ERIC Educational Resources Information Center

Nathanson, Steven A.; Nathanson, Marsha L.

2004-01-01

In this paper, we discuss the link between effective literacy practices recommended by the International Reading Association and current research on how the brain learns derived from MRI and PET scan studies begun in the 1990's. Five key areas of brain-based research discussed include time and attention, emotion, the nature of memory, the learning…

Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy.

PubMed

Russmann, Vera; Brendel, Matthias; Mille, Erik; Helm-Vicidomini, Angela; Beck, Roswitha; Günther, Lisa; Lindner, Simon; Rominger, Axel; Keck, Michael; Salvamoser, Josephine D; Albert, Nathalie L; Bartenstein, Peter; Potschka, Heidrun

2017-01-01

Excessive activation of inflammatory signaling pathways seems to be a hallmark of epileptogenesis. Positron emission tomography (PET) allows in vivo detection of brain inflammation with spatial information and opportunities for longitudinal follow-up scanning protocols. Here, we assessed whether molecular imaging of the 18 kDa translocator protein (TSPO) can serve as a biomarker for the development of epilepsy. Therefore, brain uptake of [ 18 F]GE-180, a highly selective radioligand of TSPO, was investigated in a longitudinal PET study in a chronic rat model of temporal lobe epilepsy. Analyses revealed that the influence of the epileptogenic insult on [ 18 F]GE-180 brain uptake was most pronounced in the earlier phase of epileptogenesis. Differences were evident in various brain regions during earlier phases of epileptogenesis with [ 18 F]GE-180 standardized uptake value enhanced by 2.1 to 2.7fold. In contrast, brain regions exhibiting differences seemed to be more restricted with less pronounced increases of tracer uptake by 1.8-2.5fold four weeks following status epilepticus and by 1.5-1.8fold in the chronic phase. Based on correlation analysis, we were able to identify regions with a predictive value showing a correlation with seizure development. These regions include the amygdala as well as a cluster of brain areas. This cluster comprises parts of different brain regions, e.g. the hippocampus, parietal cortex, thalamus, and somatosensory cortex. In conclusion, the data provide evidence that [ 18 F]GE-180 PET brain imaging can serve as a biomarker of epileptogenesis. The identification of brain regions with predictive value might facilitate the development of preventive concepts as well as the early assessment of the interventional success. Future studies are necessary to further confirm the predictivity of the approach.

Segmentation of 3D microPET images of the rat brain via the hybrid gaussian mixture method with kernel density estimation.

PubMed

Chen, Tai-Been; Chen, Jyh-Cheng; Lu, Henry Horng-Shing

2012-01-01

Segmentation of positron emission tomography (PET) is typically achieved using the K-Means method or other approaches. In preclinical and clinical applications, the K-Means method needs a prior estimation of parameters such as the number of clusters and appropriate initialized values. This work segments microPET images using a hybrid method combining the Gaussian mixture model (GMM) with kernel density estimation. Segmentation is crucial to registration of disordered 2-deoxy-2-fluoro-D-glucose (FDG) accumulation locations with functional diagnosis and to estimate standardized uptake values (SUVs) of region of interests (ROIs) in PET images. Therefore, simulation studies are conducted to apply spherical targets to evaluate segmentation accuracy based on Tanimoto's definition of similarity. The proposed method generates a higher degree of similarity than the K-Means method. The PET images of a rat brain are used to compare the segmented shape and area of the cerebral cortex by the K-Means method and the proposed method by volume rendering. The proposed method provides clearer and more detailed activity structures of an FDG accumulation location in the cerebral cortex than those by the K-Means method.

T156. IN VIVO CHARACTERIZATION OF THE FIRST AGONIST DOPAMINE D1 RECEPTORS PET IMAGING TRACER [18F]MNI-968 IN HUMAN

PubMed Central

Tamagnan, Gilles; Barret, Olivier; Alagille, David; Carroll, Vincent; Madonia, Jennifer; Constantinescu, Cristian; SanDiego, Christine; Papin, Caroline; Morley, Thomas; Russell, David; McCarthy, Timothy; Zhang, Lei; Gray, David; Villalobos, Anna; Lee, Chewah; Chen, Jianqing; Seibyl, John; Marek, Kenneth

2018-01-01

Abstract Background D1 receptors, which couple to inhibitory G-proteins, have been shown to regulate neuronal growth and development, mediate some behavioral responses. Its function has been shown to be altered in both neurologic and psychiatric disorders. To date, there is a lack of agonist PET tracers for the D1 receptors labeled with 18F with relevance in clinical studies. We report the evaluation in non-human primates of [18F]MNI-968 (PF-06730110), a novel PET radiotracer of the D1 receptors Methods Four brain PET studies, 2 baselines and 2 blockade studies using PF-2562, a D1 partial agonist compound, were conducted for 90 min in two rhesus monkeys with [18F]MNI-968 (169 ± 31 MBq). [18F]PF-06730110 was administered at the same dose level for both monkeys as a bolus followed by a 2-hour infusion, with [18F]MNI-968 administered 30 min into the infusion. Additionally, six brain PET studies were conducted over 180 min (317 ± 49 MBq) in 6 healthy human volunteers (3 test/retest and 3 test). PET data were modeled with 2-tissue compartmental model (2T), Logan graphical analysis (LGA), and non-invasive Logan graphical analysis (NI-LGA) with cerebellar cortex as reference region to estimate total distribution volume VT, and binding potential BPND. For the blockade studies in rhesus monkeys, occupancy was estimated from BPND at baseline and post blockade. Results In rhesus monkeys, [18F]MNI-968 (PF-06730110), penetrated the brain with a peak whole-brain uptake up to ~3% of the injected dose at ~ 6 min post injection and showed a fast washout. The highest signal was found in the caudate, putamen, with moderate extrastriatal uptake. The lowest signal was in the cerebellum. BPND values were up to ~1.4 in the putamen. All three quantification methods (2T, LGA and NI-LGA) were in excellent agreement, with a similar estimated D1 receptors occupancy of PF-06730110 of ~40% for both monkeys in the caudate and putamen. In human, [18F]MNI-968 kinetics appeared to be faster compared to non-human primates, with a BPND in the putamen of ~0.8. Initial measurement of test-retest reproducibility was ≤ 7% for BPND in the striatal regions. Discussion Our work showed that [18F]MNI-968 ([18F]PF-06730110), is a promising agonist PET radiotracer for imaging D1agnist receptors that can be quantified non-invasively. Studies are currently ongoing both in non-human and human primates to further characterize the tracer.

Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy.

PubMed

Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

2017-03-21

The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECT dist ). The method was also applied to SECT data (SECT dist ). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECT dist and SECT dist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECT Schneider ). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECT dist and 0.54, 0.41 and 0.66 for SECT dist . MC simulations of PET treatment verification in patients showed important differences between DECT dist /SECT dist and SECT Schneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECT dist and SECT dist yielded comparable activity distributions, and comparison of SECT dist to a measured patient PET scan showed improved agreement when compared to SECT Schneider . The agreement between predicted and measured PET activity distributions was improved by employing a brain specific segmentation applicable to both DECT and SECT data.

Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems.

PubMed

Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo

2014-05-01

All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted modulation of neurotransmitter networks. Copyright © 2013 Wiley Periodicals, Inc.

(18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.

PubMed

Toyonaga, Takuya; Hirata, Kenji; Yamaguchi, Shigeru; Hatanaka, Kanako C; Yuzawa, Sayaka; Manabe, Osamu; Kobayashi, Kentaro; Watanabe, Shiro; Shiga, Tohru; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Kuge, Yuji; Tamaki, Nagara

2016-07-01

Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.

Typical cerebral metabolic patterns in neurodegenerative brain diseases.

PubMed

Teune, Laura K; Bartels, Anna L; de Jong, Bauke M; Willemsen, Antoon T M; Eshuis, Silvia A; de Vries, Jeroen J; van Oostrom, Joost C H; Leenders, Klaus L

2010-10-30

The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.

PET/CT in a Patient Diagnosed With Dandy-Walker Syndrome.

PubMed

Infante, Jose R; Garcia, Lucia; Rayo, Juan I; Serrano, Justo; Dominguez, Maria L; Moreno, Manuel

2016-01-01

The Dandy-Walker syndrome (DWS) is a rare congenital posterior fossa malformation characterized by aplasia or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa. We present a 52-year-old Caucasian man diagnosed with gastrointestinal stromal tumor and submitted to 18F-FDG PET/CT as a staging procedure. The patient was previously diagnosed with DWS in brain CT scan. PET/CT images revealed an ametabolic large cyst in the posterior fossa and hypoplasia of cerebellar vermis. The case is presented with the aim to show the appearance of this syndrome on PET/CT study.

Hardware, software, and scanning issues encountered during small animal imaging of photodynamic therapy in the athymic nude rat

NASA Astrophysics Data System (ADS)

Cross, Nathan; Sharma, Rahul; Varghai, Davood; Spring-Robinson, Chandra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

2007-02-01

Small animal imaging devices are now commonly used to study gene activation and model the effects of potential therapies. We are attempting to develop a protocol that non-invasively tracks the affect of Pc 4-mediated photodynamic therapy (PDT) in a human glioma model using structural image data from micro-CT and/or micro-MR scanning and functional data from 18F-fluorodeoxy-glucose (18F-FDG) micro-PET imaging. Methods: Athymic nude rat U87-derived glioma was imaged by micro-PET and either micro-CT or micro-MR prior to Pc 4-PDT. Difficulty insuring animal anesthesia and anatomic position during the micro-PET, micro-CT, and micro-MR scans required adaptation of the scanning bed hardware. Following Pc 4-PDT the animals were again 18F-FDG micro-PET scanned, euthanized one day later, and their brains were explanted and prepared for H&E histology. Histology provided the gold standard for tumor location and necrosis. The tumor and surrounding brain functional and structural image data were then isolated and coregistered. Results: Surprisingly, both the non-PDT and PDT groups showed an increase in tumor functional activity when we expected this signal to disappear in the group receiving PDT. Co-registration of the functional and structural image data was done manually. Discussion: As expected, micro-MR imaging provided better structural discrimination of the brain tumor than micro-CT. Contrary to expectations, in our preliminary analysis 18F-FDG micro-PET imaging does not readily discriminate the U87 tumors that received Pc 4-PDT. We continue to investigate the utility of micro-PET and other methods of functional imaging to remotely detect the specificity and sensitivity of Pc 4-PDT in deeply placed tumors.

Is cerebral glucose metabolism related to blood-brain barrier dysfunction and intrathecal IgG synthesis in Alzheimer disease?: A 18F-FDG PET/CT study.

PubMed

Chiaravalloti, Agostino; Fiorentini, Alessandro; Ursini, Francesco; Martorana, Alessandro; Koch, Giacomo; Belli, Lorena; Toniolo, Sofia; Di Pietro, Barbara; Motta, Caterina; Schillaci, Orazio

2016-09-01

The aim of this study was to investigate the relationships between blood-brain barrier (BBB) dysfunction, intrathecal IgG synthesis, and brain glucose consumption as detectable by means of serum/cerebrospinal fluid (CSF) albumin index (Qalb) and IgG index [(CSF IgG/serum IgG) × Serum albumin/CSF albumin)] and 2-deoxy-2-(F) fluoro-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in a selected population affected by Alzheimer disease (AD). The study included 134 newly diagnosed AD patients according to the NINCDS-ADRDA criteria. The mean (±SD) age of the patients was 70 (±6) years; 60 were male and 64 were female. Mini mental State Examination was equal to 18.9 (±7.2). All patients underwent a CSF assay and magnetic resonance before F-FDG PET scanning. The relationships were evaluated by means of statistical parametric mapping (SPM8). We found a significant negative correlation between the increase of Qalb and F-FDG uptake in the Brodmann Area 42 and 22 that corresponds to the left superior temporal gyrus, with higher Qalb values being related to a reduced glucose consumption in these areas. No significant relationships have been found between brain glucose consumption and IgG index. The results of our study suggest that BBB dysfunction is related to reduction of cortical activity in the left temporal cortex in AD subjects.

Stereotactic Comparison Study of (18)F-Alfatide and (18)F-FDG PET Imaging in an LLC Tumor-Bearing C57BL/6 Mouse Model.

PubMed

Wei, Yu-Chun; Gao, Yongsheng; Zhang, Jianbo; Fu, Zheng; Zheng, Jinsong; Liu, Ning; Hu, Xudong; Hou, Wenhong; Yu, Jinming; Yuan, Shuanghu

2016-06-28

This study aimed to stereotactically compare the PET imaging performance of (18)F-Alfatide ((18)F-ALF-NOTA-PRGD2, denoted as (18)F-Alfatide) and (18)F-fluorodeoxyglucose (FDG) and immunohistochemistry (IHC) staining in Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. (18)F-FDG standard uptake values (SUVs) were higher than (18)F-Alfatide SUVs in tumors, most of the normal tissues and organs except for the bladder. Tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of (18)F-Alfatide PET were significantly higher than those of (18)F-FDG PET (P < 0.001). The spatial heterogeneity of the tumors was detected, and the tracer accumulation enhanced from the outer layer to the inner layer consistently using the two tracers. The parameters of the tumors were significantly correlated with each other between (18)F-FDG SUV and GLUT-1 (R = 0.895, P < 0.001), (18)F-Alfatide SUV and αvβ3 (R = 0.595, P = 0.019), (18)F-FDG SUV and (18)F-Alfatide SUV (R = 0.917, P < 0.001), and GLUT-1 and αvβ3 (R = 0.637, P = 0.011). Therefore, (18)F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to (18)F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study.

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.

SPECT and PET analysis of subthalamic stimulation in Parkinson's disease: analysis using a manual segmentation.

PubMed

Haegelen, Claire; García-Lorenzo, Daniel; Le Jeune, Florence; Péron, Julie; Gibaud, Bernard; Riffaud, Laurent; Brassier, Gilles; Barillot, Christian; Vérin, Marc; Morandi, Xavier

2010-03-01

The subthalamic nucleus (STN) has become an effective target of deep-brain stimulation (DBS) in severely disabled patients with advanced Parkinson's disease (PD). Clinical studies have reported DBS-induced adverse effects on cognitive functions, mood, emotion and behavior. STN DBS seems to interfere with the limbic functions of the basal ganglia, but the limbic effects of STN DBS are controversial. We measured prospectively resting regional cerebral metabolism (rCMb) with 18-fluorodeoxyglucose and PET, and resting regional cerebral blood flow (rCBF) with HMPAO and SPECT in six patients with Parkinson's disease. We compared PET and SPECT 1 month before and 3 months after STN DBS. On cerebral MRI, 13 regions of interest (ROI) were manually delineated slice by slice in frontal and limbic lobes. We obtained mean rCBF and rCMb values for each ROI and the whole brain. We normalized rCBF and rCMB values to ones for the whole brain volume, which we compared before and following STN DBS. No significant difference emerged in the SPECT analysis. PET analysis revealed a significant decrease in rCMb following STN DBS in the superior frontal gyri and left and right dorsolateral prefrontal cortex (p < 0.05). A non-significant decrease in rCMb in the left anterior cingulate gyrus appeared following STN DBS (p = 0.075). Our prospective SPECT and PET study revealed significantly decreased glucose metabolism of the two superior frontal gyri without any attendant perfusion changes following STN DBS. These results suggest that STN DBS may change medial prefrontal function and therefore the integration of limbic information, either by disrupting emotional processes within the STN, or by hampering the normal function of a limbic circuit.

Construction and comparative evaluation of different activity detection methods in brain FDG-PET.

PubMed

Buchholz, Hans-Georg; Wenzel, Fabian; Gartenschläger, Martin; Thiele, Frank; Young, Stewart; Reuss, Stefan; Schreckenberger, Mathias

2015-08-18

We constructed and evaluated reference brain FDG-PET databases for usage by three software programs (Computer-aided diagnosis for dementia (CAD4D), Statistical Parametric Mapping (SPM) and NEUROSTAT), which allow a user-independent detection of dementia-related hypometabolism in patients' brain FDG-PET. Thirty-seven healthy volunteers were scanned in order to construct brain FDG reference databases, which reflect the normal, age-dependent glucose consumption in human brain, using either software. Databases were compared to each other to assess the impact of different stereotactic normalization algorithms used by either software package. In addition, performance of the new reference databases in the detection of altered glucose consumption in the brains of patients was evaluated by calculating statistical maps of regional hypometabolism in FDG-PET of 20 patients with confirmed Alzheimer's dementia (AD) and of 10 non-AD patients. Extent (hypometabolic volume referred to as cluster size) and magnitude (peak z-score) of detected hypometabolism was statistically analyzed. Differences between the reference databases built by CAD4D, SPM or NEUROSTAT were observed. Due to the different normalization methods, altered spatial FDG patterns were found. When analyzing patient data with the reference databases created using CAD4D, SPM or NEUROSTAT, similar characteristic clusters of hypometabolism in the same brain regions were found in the AD group with either software. However, larger z-scores were observed with CAD4D and NEUROSTAT than those reported by SPM. Better concordance with CAD4D and NEUROSTAT was achieved using the spatially normalized images of SPM and an independent z-score calculation. The three software packages identified the peak z-scores in the same brain region in 11 of 20 AD cases, and there was concordance between CAD4D and SPM in 16 AD subjects. The clinical evaluation of brain FDG-PET of 20 AD patients with either CAD4D-, SPM- or NEUROSTAT-generated databases from an identical reference dataset showed similar patterns of hypometabolism in the brain regions known to be involved in AD. The extent of hypometabolism and peak z-score appeared to be influenced by the calculation method used in each software package rather than by different spatial normalization parameters.

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.

Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

PubMed

Hou, Haifeng; Tian, Mei; Zhang, Hong

2012-05-01

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Copyright © 2012 Wiley Periodicals, Inc.

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia.

PubMed

Akamatsu, Go; Ohnishi, Akihito; Aita, Kazuki; Ikari, Yasuhiko; Yamamoto, Yasuji; Senda, Michio

2017-01-01

Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-β pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET. Each amyloid PET agent has its own proper administration instructions and recommended uptake time, scan duration, and the method of image display and interpretation. In addition, we have introduced general scanning information, including subject positioning, reconstruction parameters, and quantitative and statistical image analysis. We believe that this article could make amyloid PET a more reliable tool in clinical study and practice.

Performance modeling of a wearable brain PET (BET) camera

NASA Astrophysics Data System (ADS)

Schmidtlein, C. R.; Turner, J. N.; Thompson, M. O.; Mandal, K. C.; Häggström, I.; Zhang, J.; Humm, J. L.; Feiglin, D. H.; Krol, A.

2016-03-01

Purpose: To explore, by means of analytical and Monte Carlo modeling, performance of a novel lightweight and low-cost wearable helmet-shaped Brain PET (BET) camera based on thin-film digital Geiger Avalanche Photo Diode (dGAPD) with LSO and LaBr3 scintillators for imaging in vivo human brain processes for freely moving and acting subjects responding to various stimuli in any environment. Methods: We performed analytical and Monte Carlo modeling PET performance of a spherical cap BET device and cylindrical brain PET (CYL) device, both with 25 cm diameter and the same total mass of LSO scintillator. Total mass of LSO in both the BET and CYL systems is about 32 kg for a 25 mm thick scintillator, and 13 kg for 10 mm thick scintillator (assuming an LSO density of 7.3 g/ml). We also investigated a similar system using an LaBr3 scintillator corresponding to 22 kg and 9 kg for the 25 mm and 10 mm thick systems (assuming an LaBr3 density of 5.08 g/ml). In addition, we considered a clinical whole body (WB) LSO PET/CT scanner with 82 cm ring diameter and 15.8 cm axial length to represent a reference system. BET consisted of distributed Autonomous Detector Arrays (ADAs) integrated into Intelligent Autonomous Detector Blocks (IADBs). The ADA comprised of an array of small LYSO scintillator volumes (voxels with base a×a: 1.0 <= a <= 2.0 mm and length c: 3.0 <= c <= 6.0 mm) with 5-65 μm thick reflective layers on its five sides and sixth side optically coupled to the matching array of dGAPDs and processing electronics with total thickness of 50 μm. Simulated energy resolution was 10.8% and 3.3% for LSO and LaBr3 respectively and the coincidence window was set at 2 ns. The brain was simulated as a sphere of uniform F-18 activity with diameter of 10 cm embedded in a center of water sphere with diameter of 10 cm. Results: Analytical and Monte Carlo models showed similar results for lower energy window values (458 keV versus 445 keV for LSO, and 492 keV versus 485 keV for LaBr3), and for the relative performance of system sensitivity. Monte Carlo results further showed that the BET geometry had >50% better noise equivalent count (NEC) performance relative to the CYL geometry, and >1100% better performance than a WB geometry for 25 mm thick LSO and LaBr3. For 10 mm thick LaBr3 equivalent mass systems LSO (7 mm thick) performed ~40% higher NEC than LaBr3. Analytic and Monte Carlo simulations also showed that 1×1×3 mm scintillator crystals can achieve ~1.2 mm FWHM spatial resolution. Conclusions: This study shows that a spherical cap brain PET system can provide improved NEC while preserving spatial resolution when compared to an equivalent dedicated cylindrical PET brain camera and shows greatly improved PET performance relative to a conventional whole body PET/CT. In addition, our simulations show that LSO will generally outperform LaBr3 for NEC unless the timing resolution for LaBr3 is considerably smaller than presently used for LSO, i.e. well below 300 ps.

Brain and Brown Adipose Tissue Metabolism in Transgenic Tg2576 Mice Models of Alzheimer Disease Assessed Using 18F-FDG PET Imaging

PubMed Central

Coleman, Robert A.; Liang, Christopher; Patel, Rima; Ali, Sarah

2017-01-01

Objective: Imaging animal models of Alzheimer disease (AD) is useful for the development of therapeutic drugs and understanding AD. Transgenic Swedish hAPPswe Tg2576 mice are a good model of β-amyloid plaques. We report 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) imaging of brain and intrascapular brown adipose tissue (IBAT) in transgenic mice 2576 (Tg2576) and wild-type (WT) mice. Methods: Transgenic Tg2576 mice and WT mice, >18 months were injected intraperitonally with ≈ 25 to 30 MBq 18F-FDG while awake. After 60 minutes, they were anesthetized with isoflurane (2.5%) and imaged with Inveon MicroPET. Select mice were killed, imaged ex vivo, and 20 µm sections cut for autoradiography. 18F-FDG uptake in brain and IBAT PET and brain autoradiographs were analyzed. Results: Fasting blood glucose levels averaged 120 mg/dL for WT and 100 mg/dL for Tg2576. Compared to WT, Tg2576 mice exhibited a decrease in SUVglc in the various brain regions. Average reductions in the cerebrum regions were as high as −20%, while changes in cerebellum were −3%. Uptake of 18F-FDG in IBAT decreased by −60% in Tg2576 mice and was found to be significant. Intrascapular brown adipose tissue findings in Tg2576 mice are new and not previously reported. Use of blood glucose for PET data analysis and corpus callosum as reference region for autoradiographic analysis were important to detect change in Tg2576 mice. Conclusion: Our results suggest that 18F-FDG uptake in the Tg2576 mice brain show 18F-FDG deficits only when blood glucose is taken into consideration. PMID:28654383

11C-Methionine Positron Emission Tomography/Computed Tomography Versus 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Evaluation of Residual or Recurrent World Health Organization Grades II and III Meningioma After Treatment.

PubMed

Tomura, Noriaki; Saginoya, Toshiyuki; Goto, Hiromi

2018-04-02

The aim of this study was to determine the assessment of positron emission tomography-computed tomography using C-methionine (MET PET/CT) for World Health Organization (WHO) grades II and III meningiomas; MET PET/CT was compared with PET/CT using F-fluorodeoxy glucose (FDG PET/CT). This study was performed in 17 cases with residual and/or recurrent WHO grades II and III meningiomas. Two neuroradiologists reviewed both PET/CT scans. For agreement, the κ coefficient was measured. Difference in tumor-to-normal brain uptake ratios (T/N ratios) between 2 PET/CT scans was analyzed. Correlation between the maximum tumor size and T/N ratio in PET/CT was studied. For agreement by both reviewers, the κ coefficient was 0.51 (P < 0.05). The T/N ratio was significantly higher for MET PET/CT (3.24 ± 1.36) than for FDG PET/CT (0.93 ± 0.44) (P < 0.01). C-methionine ratio significantly correlated with tumor size (y = 8.1x + 16.3, n = 22, P < 0.05), but FDG ratio did not CONCLUSIONS: C-methionine PET/CT has superior potential for imaging of WHO grades II and III meningiomas with residual or recurrent tumors compared with FDG PET/CT.

MRI and PET Compatible Bed for Direct Co-Registration in Small Animals

NASA Astrophysics Data System (ADS)

Bartoli, Antonietta; Esposito, Giovanna; D'Angeli, Luca; Chaabane, Linda; Terreno, Enzo

2013-06-01

To obtain an accurate co-registration with stand-alone PET and MRI scanners, we developed a compatible bed system for mice and rats that enables both images to be acquired without repositioning the animals. MRI acquisitions were performed on a preclinical 7T scanner (Pharmascan, Bruker), whereas PET scans were acquired on a YAP-(S)PET (ISE s.r.l.). The bed performance was tested both on a phantom (NEMA Image Quality phantom) and in vivo (healthy rats and mice brain). Fiducial markers filled up with a drop of 18 F were visible in both modalities. Co-registration process was performed using the point-based registration technique. The reproducibility and accuracy of the co-registration were assessed using the phantom. The reproducibility of the translation distances was 0.2 mm along the z axis. On the other hand, the accuracy depended on the physical size of the phantom structures under investigation but was always lower than 4%. Regions of Interest (ROIs) drawn on the fused images were used for quantification purposes. PET and MRI intensity profiles on small structures of the phantom showed that the underestimation in activity concentration reached 90% in regions that were smaller than the PET spatial resolution, while the MRI allowed a good visualization of the 1 mm 0 rod. PET/MRI images of healthy mice and rats highlighted the expected superior capability of MRI to define brain structures. The simplicity of our developed MRI/PET compatible bed and the quality of the fused images obtained offers a promising opportunity for a future preclinical translation, particularly for neuroimaging studies.

Motion correction of PET brain images through deconvolution: II. Practical implementation and algorithm optimization

NASA Astrophysics Data System (ADS)

Raghunath, N.; Faber, T. L.; Suryanarayanan, S.; Votaw, J. R.

2009-02-01

Image quality is significantly degraded even by small amounts of patient motion in very high-resolution PET scanners. When patient motion is known, deconvolution methods can be used to correct the reconstructed image and reduce motion blur. This paper describes the implementation and optimization of an iterative deconvolution method that uses an ordered subset approach to make it practical and clinically viable. We performed ten separate FDG PET scans using the Hoffman brain phantom and simultaneously measured its motion using the Polaris Vicra tracking system (Northern Digital Inc., Ontario, Canada). The feasibility and effectiveness of the technique was studied by performing scans with different motion and deconvolution parameters. Deconvolution resulted in visually better images and significant improvement as quantified by the Universal Quality Index (UQI) and contrast measures. Finally, the technique was applied to human studies to demonstrate marked improvement. Thus, the deconvolution technique presented here appears promising as a valid alternative to existing motion correction methods for PET. It has the potential for deblurring an image from any modality if the causative motion is known and its effect can be represented in a system matrix.

Encoding-related brain activity during deep processing of verbal materials: a PET study.

PubMed

Fujii, Toshikatsu; Okuda, Jiro; Tsukiura, Takashi; Ohtake, Hiroya; Suzuki, Maki; Kawashima, Ryuta; Itoh, Masatoshi; Fukuda, Hiroshi; Yamadori, Atsushi

2002-12-01

The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.

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.

Discovery of Phosphodiesterase 10A (PDE10A) PET Tracer AMG 580 to Support Clinical Studies.

PubMed

Hu, Essa; Chen, Ning; Kunz, Roxanne K; Hwang, Dah-Ren; Michelsen, Klaus; Davis, Carl; Ma, Ji; Shi, Jianxia; Lester-Zeiner, Dianna; Hungate, Randall; Treanor, James; Chen, Hang; Allen, Jennifer R

2016-07-14

We report the discovery of PDE10A PET tracer AMG 580 developed to support proof of concept studies with PDE10A inhibitors in the clinic. To find a tracer with higher binding potential (BPND) in NHP than our previously reported tracer 1, we implemented a surface plasmon resonance assay to measure the binding off-rate to identify candidates with slower washout rate in vivo. Five candidates (2-6) from two structurally distinct scaffolds were identified that possessed both the in vitro characteristics that would favor central penetration and the structural features necessary for PET isotope radiolabeling. Two cinnolines (2, 3) and one keto-benzimidazole (5) exhibited PDE10A target specificity and brain uptake comparable to or better than 1 in the in vivo LC-MS/MS kinetics distribution study in SD rats. In NHP PET imaging study, [(18)F]-5 produced a significantly improved BPND of 3.1 and was nominated as PDE10A PET tracer clinical candidate for further studies.

The impact of 18 F-FET PET-CT on target definition in image-guided stereotactic radiotherapy in patients with skull base lesions.

PubMed

Badakhshi, Harun; Graf, Reinhold; Prasad, Vikas; Budach, Volker

2014-06-25

18 F-fluoro-ethyl-tyrosine PET is gaining more indications in the field of oncology. We investigated the potentials of usage of FET-PET/CT in addition to MRI for definition of gross tumor volume (GTV) in stereotactic radiotherapy of lesions of skull base. We included in a prospective setting 21 cases. An MRI was performed, completed by FET PET/CT. Different GTV's were defined based on respective imaging tools: 1. GTVMRI, 2. GTV MRI /CT, 3. GTV composit (1 + 2), and GTVPET = GTV Boost. Lesions could be visualised by MRI and FET-PET/CT in all patients. FET tracer enhancement was found in all cases. Skull base infiltration by these lesions was observed by MRI, CT (PET/CT) and FET-PET (PET/CT) in all patients. Totally, brain tissue infiltration was seen in 10 patients. While, in 7 (out 10) cases, MRI and CT (from PET/CT) were indicating brain infiltration, FET-PET could add additional information regarding infiltrative behaviour: in 3 (out 10) patients, infiltration of the brain was displayed merely in FET-PET. An enlargement of GTVMRI/CT due to the FET-PET driven information, which revealed GTVcomposite , was necessary in 7 cases,. This enlargement was significant by definition (> 10% of GTVMRI/CT). The mean PET-effect on GTV counted for 1 ± 4 cm3. The restricted boost fields were based mainly on the GTVPET volume. In mean, about 8.5 cm3 of GTVMRI/CT, which showed no FET uptake, were excluded from target volume. GTV boost driven by only-PET-activity, was in mean by 33% smaller than the initial large treatment field, GTV composite, for those cases received boost treatment. FET-PET lead to significant (>10%) changes in the initial treatment fields in 11/21 patients and showed additional tumour volume relevant for radiation planning in 6/21 cases, and led to a subsequent decrease of more than 10% of the initial volumes for the boost fields. The implementation of FET PET into the planning procedures showed a benefit in terms of accurate definition of skull base lesions as targets for Image-guided stereotactic Radiotherapy. This has to be investigated prospectively in larger cohorts.

Effects of Long-Term Caffeine Consumption on the Adenosine A1 Receptor in the Rat Brain: an In Vivo PET Study with [18F]CPFPX.

PubMed

Nabbi-Schroeter, Danje; Elmenhorst, David; Oskamp, Angela; Laskowski, Stefanie; Bauer, Andreas; Kroll, Tina

2018-04-01

Caffeine, a nonselective antagonist of adenosine receptors, is the most popular psychostimulant worldwide. Recently, a protective role of moderate chronic caffeine consumption against neurodegenerative diseases such as Alzheimer's and Parkinson's disease has been discussed. Thus, aim of the present study was an in vivo investigation of effects of long-term caffeine consumption on the adenosine A 1 receptor (A 1 AR) in the rat brain. Sixteen adult, male rats underwent five positron emission tomography (PET) scans with the highly selective A 1 AR radioligand [ 18 F]CPFPX in order to determine A 1 AR availability. After the first baseline PET scan, the animals were assigned to two groups: Caffeine treatment and control group. The caffeine-treated animals received caffeinated tap water (30 mg/kg bodyweight/day, corresponding to 4-5 cups of coffee per day in humans) for 12 weeks. Subsequently, caffeine was withdrawn and repeated PET measurements were performed on day 1, 2, 4, and 7 of caffeine withdrawal. The control animals were measured according to the same time schedule. At day 1, after 4.4 h of caffeine withdrawal, a significant decrease (- 34.5%, p < 0.001) of whole brain A 1 AR availability was observed. Unlike all other investigated brain regions in caffeine-treated rats, the hypothalamus and nucleus accumbens showed no significant intraindividual differences between baseline and first withdrawal PET scan. After approximately 27 h of caffeine withdrawal, the region- and group-specific effects disappeared and A 1 AR availability settled around baseline. The present study provides evidence that chronic caffeine consumption does not lead to persistent changes in functional availability of cerebral A 1 ARs which have previously been associated with neuroprotective effects of caffeine. The acute and region-specific decrease in cerebral A 1 AR availability directly after caffeine withdrawal is most likely caused by residual amounts of caffeine metabolites disguising an unchanged A 1 AR expression at this early time-point.

Radiosynthesis of the candidate beta-amyloid radioligand [(11)C]AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys.

PubMed

Andersson, Jan D; Varnäs, Katarina; Cselényi, Zsolt; Gulyás, Balázs; Wensbo, David; Finnema, Sjoerd J; Swahn, Britt-Marie; Svensson, Samuel; Nyberg, Svante; Farde, Lars; Halldin, Christer

2010-10-01

Beta-amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high-contrast positron emission tomography (PET) imaging of Abeta-deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon-11, to perform in vivo characterization of [(11)C]AZD2184 ([(11)C]5) in the cynomolgus monkey brain as well as whole-body dosimetry, and to examine the metabolism of the labeled radioligand. [(11)C]5 was prepared by a two-step radiosynthesis starting with the reaction of 5-(6-(tert-butyldimethylsilyloxy)benzo[d]thiazol-2-yl)pyridin-2-amine with [(11)C]methyl iodide followed by deprotection using water. Four brain PET measurements in two cynomolgus monkeys and one whole-body PET measurement were performed with [(11)C]5. There was a high and rapid brain uptake (2.2-3.4% of injected dose at 2 min). The distribution of brain radioactivity was fairly uniform, with early to late-brain concentration ratios (peak vs. 60 min) higher for [(11)C]5 than ratios previously reported for [(11)C]PIB (8.2 and 4.6, respectively). Based on the whole-body data, it was estimated that an effective dose in an adult male would be 6.2 muSv/MBq and thus would be safe from a radiation point of view for multiple scans within the same year. [(11)C]5 shows binding characteristics, suggesting low levels of white-matter retention, and may thus provide improved contrast when compared with currently used PET radioligands for visualization of Abeta-deposits. On the basis of the labeling chemistry and the results of the biological evaluation, we conclude that [(11)C]5 should be useful for routine clinical studies. (c) 2010 Wiley-Liss, Inc.

Communication among neurons.

PubMed

Marner, Lisbeth

2012-04-01

The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are considered and the relation to the prevailing beta-amyloid hypothesis is discussed.

Acute marijuana effects on rCBF and cognition: a PET study.

PubMed

O'Leary, D S; Block, R I; Flaum, M; Schultz, S K; Boles Ponto, L L; Watkins, G L; Hurtig, R R; Andreasen, N C; Hichwa, R D

2000-11-27

The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

Postmortem 3-D brain hemisphere cortical tau and amyloid-β pathology mapping and quantification as a validation method of neuropathology imaging.

PubMed

Smid, Lojze M; Kepe, Vladimir; Vinters, Harry V; Bresjanac, Mara; Toyokuni, Tatsushi; Satyamurthy, Nagichettiar; Wong, Koon-Pong; Huang, Sung-Cheng; Silverman, Daniel H S; Miller, Karen; Small, Gary W; Barrio, Jorge R

2013-01-01

This work is aimed at correlating pre-mortem [18F]FDDNP positron emission tomography (PET) scan results in a patient with dementia with Lewy bodies (DLB), with cortical neuropathology distribution determined postmortem in three physical dimensions in whole brain coronal sections. Analysis of total amyloid-β (Aβ) distribution in frontal cortex and posterior cingulate gyrus confirmed its statistically significant correlation with cortical [18F]FDDNP PET binding values (distribution volume ratios, DVR) (p < 0.001, R = 0.97, R2 = 0.94). Neurofibrillary tangle (NFT) distribution correlated significantly with cortical [18F]FDDNP PET DVR in the temporal lobe (p < 0.001, R = 0.87, R2 = 0.76). Linear combination of Aβ and NFT densities was highly predictive of [18F]FDDNP PET DVR through all analyzed regions of interest (p < 0.0001, R = 0.92, R2 = 0.85), and both densities contributed significantly to the model. Lewy bodies were present at a much lower level than either Aβ or NFTs and did not significantly contribute to the in vivo signal. [18F]FDG PET scan results in this patient were consistent with the distinctive DLB pattern of hypometabolism. This work offers a mapping brain model applicable to all imaging probes for verification of imaging results with Aβ and/or tau neuropathology brain distribution using immunohistochemistry, fluorescence microscopy, and autoradiography.

F-18 choline PET does not detect increased metabolism in F-18 fluoroethyltyrosine-negative low-grade gliomas.

PubMed

Roelcke, Ulrich; Bruehlmeier, Matthias; Hefti, Martin; Hundsberger, Thomas; Nitzsche, Egbert U

2012-01-01

Positron emission tomography (PET) with radiolabeled amino acids provides information on biopsy target and chemotherapy response in patients with low-grade gliomas (LGG). In this article, we addressed whether PET with F-18 choline (CHO) detects increased metabolism in F-18 fluoroethyltyrosine (FET)-negative LGG patients. Six LGG patients with nongadolinium-enhancing (magnetic resonance) FET-negative LGG were imaged with CHO PET. Regions of interest were positioned over tumor and contralateral brain. Uptake of FET and CHO was quantified as count ratio of tumor to contralateral brain. The mean FET uptake ratio for FET-negative LGG was 0.95 ± 0.03 (mean ± standard deviation). Five tumors did not show increased uptake ratios for CHO (0.96 ± 0.12). Slightly increased CHO uptake was found in 1 patient (1.24), which, however, was not associated with tumor visualization. Amino acid and choline uptake appear to behave similar in nongadolinium-enhancing LGG. For clinical purposes, CHO PET is not superior to FET PET.

Discriminative Power of Arterial Spin Labeling Magnetic Resonance Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Changes for Amyloid-β-Positive Subjects in the Alzheimer's Disease Continuum.

PubMed

Tosun, Duygu; Schuff, Norbert; Jagust, William; Weiner, Michael W

2016-01-01

Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-β-positive (Aβ+) subjects in the AD continuum from healthy controls. The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Aβ based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Aβ+ subjects in the early disease stages from the Aβ- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Aβ+ subjects from the Aβ- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum. © 2015 S. Karger AG, Basel.

Influence of O-methylated metabolite penetrating the blood-brain barrier to estimation of dopamine synthesis capacity in human L-[β-(11)C]DOPA PET.

PubMed

Matsubara, Keisuke; Ikoma, Yoko; Okada, Maki; Ibaraki, Masanobu; Suhara, Tetsuya; Kinoshita, Toshibumi; Ito, Hiroshi

2014-02-01

O-methyl metabolite (L-[β-(11)C]OMD) of (11)C-labeled L-3,4-dihydroxyphenylalanine (L-[β-(11)C]DOPA) can penetrate into brain tissue through the blood-brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[β-(11)C]DOPA. We evaluated the impact of L-[β-(11)C]OMD on the estimation of the dopamine synthesis capacity in a human L-[β-(11)C]DOPA PET study. The metabolite correction with mathematical modeling of L-[β-(11)C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [(18)F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[β-(11)C]OMD in 10 normal volunteers. The component of L-[β-(11)C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[β-(11)C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate (kref) was estimated by Gjedde-Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate (Ki) by Gjedde-Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[β-(11)C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.

Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

NASA Astrophysics Data System (ADS)

Casey, Kenneth L.

1999-07-01

Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

Kinetic analysis of central ( sup 11 C)raclopride binding to D2-dopamine receptors studied by PET--a comparison to the equilibrium analysis

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

Farde, L.; Eriksson, L.; Blomquist, G.

1989-10-01

(11C)Raclopride binding to central D2-dopamine receptors in humans has previously been examined by positron emission tomography (PET). Based on the rapid occurrence of binding equilibrium, a saturation analysis has been developed for the determination of receptor density (Bmax) and affinity (Kd). For analysis of PET measurements obtained with other ligands, a kinetic three-compartment model has been used. In the present study, the brain uptake of (11C)raclopride was analyzed further by applying both a kinetic and an equilibrium analysis to data obtained from four PET experiments in each of three healthy subjects. First regional CBV was determined. In the second andmore » third experiment, (11C)-raclopride with high and low specific activity was used. In a fourth experiment, the (11C)raclopride enantiomer (11C)FLB472 was used to examine the concentration of free radioligand and nonspecific binding in brain. Radio-activity in arterial blood was measured using an automated blood sampling system. Bmax and Kd values for (11C)raclopride binding could be determined also with the kinetic analysis. As expected theoretically, those values were similar to those obtained with the equilibrium analysis. In addition, the kinetic analysis allowed separate determination of the association and dissociation rate constants, kon and koff, respectively. Examination of (11C)raclopride and (11C)FLB472 uptake in brain regions devoid of specific D2-dopamine receptor binding indicated a fourth compartment in which uptake was reversible, nonstereoselective, and nonsaturable in the dose range studied.« less

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.

Small-animal PET study of adenosine A(1) receptors in rat brain: blocking receptors and raising extracellular adenosine.

PubMed

Paul, Soumen; Khanapur, Shivashankar; Rybczynska, Anna A; Kwizera, Chantal; Sijbesma, Jurgen W A; Ishiwata, Kiichi; Willemsen, Antoon T M; Elsinga, Philip H; Dierckx, Rudi A J O; van Waarde, Aren

2011-08-01

Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-(11)C-methyl-3-propyl-xanthine ((11)C-MPDX) and PET. This study aims to test whether (11)C-MPDX can be used for quantitative studies of cerebral A(1)R in rodents. (11)C-MPDX was injected (intravenously) into isoflurane-anesthetized male Wistar rats (300 g). A dynamic scan of the central nervous system was obtained, using a small-animal PET camera. A cannula in a femoral artery was used for blood sampling. Three groups of animals were studied: group 1, controls (saline-treated); group 2, animals pretreated with the A(1)R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 mg, intraperitoneally); and group 3, animals pretreated (intraperitoneally) with a 20% solution of ethanol in saline (2 mL) plus the adenosine kinase inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d] pyrimidine dihydrochloride (ABT-702) (1 mg). DPCPX is known to occupy cerebral A(1)R, whereas ethanol and ABT-702 increase extracellular adenosine. In groups 1 and 3, the brain was clearly visualized. High uptake of (11)C-MPDX was noted in striatum, hippocampus, and cerebellum. In group 2, tracer uptake was strongly suppressed and regional differences were abolished. The treatment of group 3 resulted in an unexpected 40%-45% increase of the cerebral uptake of radioactivity as indicated by increases of PET standardized uptake value, distribution volume from Logan plot, nondisplaceable binding potential from 2-tissue-compartment model fit, and standardized uptake value from a biodistribution study performed after the PET scan. The partition coefficient of the tracer (K(1)/k(2) from the model fit) was not altered under the study conditions. (11)C-MPDX shows a regional distribution in rat brain consistent with binding to A(1)R. Tracer binding is blocked by the selective A(1)R antagonist DPCPX. Pretreatment of animals with ethanol and adenosine kinase inhibitor increases (11)C-MPDX uptake. This increase may reflect an increased availability of A(1)R after acute exposure to ethanol.

A multi-atlas based method for automated anatomical Macaca fascicularis brain MRI segmentation and PET kinetic extraction.

PubMed

Ballanger, Bénédicte; Tremblay, Léon; Sgambato-Faure, Véronique; Beaudoin-Gobert, Maude; Lavenne, Franck; Le Bars, Didier; Costes, Nicolas

2013-08-15

MRI templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate PET studies. Segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. We present a set of atlases manually delineated on brain MRI scans of the monkey Macaca fascicularis. We use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on MRI and extracting regional PET measures. Twelve individual Macaca fascicularis high-resolution 3DT1 MR images were acquired. Four individual atlases were created by manually drawing 42 anatomical structures, including cortical and sub-cortical structures, white matter regions, and ventricles. To create the MRI template, we first chose one MRI to define a reference space, and then performed a two-step iterative procedure: affine registration of individual MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs. Automated segmentation in native space was obtained in two ways: 1) Maximum probability atlases were created by decision fusion of two to four individual atlases in the reference space, and transformation back into the individual native space (MAXPROB)(.) 2) One to four individual atlases were registered directly to the individual native space, and combined by decision fusion (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the volume difference. The robustness and reproducibility of PET regional measurements obtained via automated segmentation was evaluated on four co-registered MRI/PET datasets, which included test-retest data. Dice indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with all four individual atlases. There was no significant mean volume bias. The standard deviation of the bias decreased significantly when increasing the number of individual atlases. MAXPROB performed better when increasing the number of atlases used. When all four atlases were used for the MAXPROB creation, the accuracy of morphometric segmentation approached that of the PROPAG method. PET measures extracted either via automatic methods or via the manually defined regions were strongly correlated, with no significant regional differences between methods. Intra-class correlation coefficients for test-retest data were over 0.87. Compared to single atlas extractions, multi-atlas methods improve the accuracy of region definition. They also perform comparably to manually defined regions for PET quantification. Multiple atlases of Macaca fascicularis brains are now available and allow reproducible and simplified analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

Gender differences in cerebral metabolism for color processing in mice: A PET/MRI Study.

PubMed

Njemanze, Philip C; Kranz, Mathias; Amend, Mario; Hauser, Jens; Wehrl, Hans; Brust, Peter

2017-01-01

Color processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women. The present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition. PET revealed a reverse pattern relative to dark condition compared to previous human studies: Male mice presented with left visual cortex dominance for blue through the right eye, while female mice presented with right visual cortex dominance for blue through the left eye. We applied statistical parametric mapping (SPM) to examine gender differences in activated architectonic areas within the orbital and medial prefrontal cortex and related cortical and sub-cortical areas that lead to the striatum, medial thalamus and other brain areas. The metabolic connectivity of the orbital and medial prefrontal cortex evoked by blue stimulation spread through a wide range of brain structures implicated in viscerosensory and visceromotor systems in the left intra-hemispheric regions in male, but in the right-to-left inter-hemispheric regions in female mice. Color functional ocular dominance plasticity was noted in the right eye in male mice but in the left eye in female mice. This study of color processing in an animal model could be applied in the study of the role of gender differences in brain disease.

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer.

PubMed

Ulaner, Gary A; Lyashchenko, Serge K; Riedl, Christopher; Ruan, Shutian; Zanzonico, Pat B; Lake, Diana; Jhaveri, Komal; Zeglis, Brian; Lewis, Jason S; O'Donoghue, Joseph A

2018-06-01

In what we believe to be a first-in-human study, we evaluated the safety and dosimetry of 89 Zr-pertuzumab PET/CT for human epidermal growth factor receptor 2 (HER2)-targeted imaging in patients with HER2-positive breast cancer. Methods: Patients with HER2-positive breast cancer and evidence of distant metastases were enrolled in an institutional review board-approved prospective clinical trial. Pertuzumab was conjugated with deferoxamine and radiolabeled with 89 Zr. Patients underwent PET/CT with 74 MBq of 89 Zr-pertuzumab in a total antibody mass of 20-50 mg of pertuzumab. PET/CT, whole-body probe counts, and blood drawing were performed over 8 d to assess pharmacokinetics, biodistribution, and dosimetry. PET/CT images were evaluated for the ability to visualize HER2-positive metastases. Results: Six patients with HER2-positive metastatic breast cancer were enrolled and administered 89 Zr-pertuzumab. No toxicities occurred. Dosimetry estimates from OLINDA demonstrated that the organs receiving the highest doses (mean ± SD) were the liver (1.75 ± 0.21 mGy/MBq), the kidneys (1.27 ± 0.28 mGy/MBq), and the heart wall (1.22 ± 0.16 mGy/MBq), with an average effective dose of 0.54 ± 0.07 mSv/MBq. PET/CT demonstrated optimal imaging 5-8 d after administration. 89 Zr-pertuzumab was able to image multiple sites of malignancy and suggested that they were HER2-positive. In 2 patients with both known HER2-positive and HER2-negative primary breast cancers and brain metastases, 89 Zr-pertuzumab PET/CT suggested that the brain metastases were HER2-positive. In 1 of the 2 patients, subsequent resection of a brain metastasis proved HER2-positive disease, confirming that the 89 Zr-pertuzumab avidity was a true-positive result for HER2-positive malignancy. Conclusion: This first-in-human study demonstrated safety, dosimetry, biodistribution, and successful HER2-targeted imaging with 89 Zr-pertuzumab PET/CT. Potential clinical applications include assessment of the HER2 status of lesions that may not be accessible to biopsy and assessment of HER2 heterogeneity. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [(11)C]Iomazenil in healthy human subjects.

PubMed

Bremner, J D; Horti, A; Staib, L H; Zea-Ponce, Y; Soufer, R; Charney, D S; Baldwin, R

2000-01-01

Quantitation of the PET benzodiazepine receptor antagonist, [(11)C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [(11)C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (>100 Ci/mmol) [(11)C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V(3)'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V(3)', were similar to results obtained with the SPECT radioligand [(123)I]iomazenil, and a prior report with low specific activity [(11)C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [(11)C]Iomazenil provides a reliable measure of benzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley-Liss, Inc.

Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar.

PubMed

Kreisl, William C; Bhatia, Ritwik; Morse, Cheryl L; Woock, Alicia E; Zoghbi, Sami S; Shetty, H Umesha; Pike, Victor W; Innis, Robert B

2015-01-01

The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier, and its resultant spare capacity requires substantial blockade to increase the uptake of avid substrates, blunting the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined 2 P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and 2 routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate (11)C-N-desmethyl-loperamide (dLop) while avoiding side effects associated with high doses of tariquidar. Forty-two (11)C-dLop PET scans were obtained from 37 healthy volunteers. PET was performed with (11)C-dLop under the following 5 conditions: injected under baseline conditions without P-gp inhibition, injected 1 h after intravenous tariquidar infusion, injected during intravenous tariquidar infusion, injected after oral tariquidar, and injected after disulfiram. (11)C-dLop uptake was quantified with kinetic modeling using metabolite-corrected arterial input function or by measuring the area under the time-activity curve in the brain from 10 to 30 min. Neither oral tariquidar nor oral disulfiram increased brain uptake of (11)C-dLop. Injecting (11)C-dLop during tariquidar infusion, when plasma tariquidar concentrations reach their peak, resulted in a brain uptake of the radioligand approximately 5-fold greater than baseline. Brain uptake was similar with 2 and 4 mg of intravenous tariquidar per kilogram; however, the lower dose was better tolerated. Injecting (11)C-dLop after tariquidar infusion also increased brain uptake, though higher doses (up to 6 mg/kg) were required. Brain uptake of (11)C-dLop increased fairly linearly with increasing plasma tariquidar concentrations, but we are uncertain whether maximal uptake was achieved. We sought to increase the dynamic range of P-gp function measured after blockade. Performing (11)C-dLop PET during peak plasma concentrations of tariquidar, achieved with concurrent administration of intravenous tariquidar, resulted in greater P-gp inhibition at the human blood-brain barrier than delayed administration and allowed the use of a lower, more tolerable dose of tariquidar. On the basis of prior monkey studies, we suspect that plasma concentrations of tariquidar did not fully block P-gp; however, higher doses of tariquidar would likely be associated with unacceptable side effects. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography

PubMed Central

Pike, Victor W.; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepción; Statnick, Michael A.; Kimura, Yasuyuki; Hong, Jinsoo; Zoghbi, Sami S.; Fujita, Masahiro; Toledo, Miguel A.; Diaz, Nuria; Gackenheimer, Susan L.; Tauscher, Johannes T.; Barth, Vanessa N.; Innis, Robert B.

2011-01-01

Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by 11C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [11C](S)-10a–c, gave similar results. Baseline scans showed high entry of radioactivity into brain to give a distribution reflecting that expected for NOP receptors. Pre-block experiments showed high early peak levels of brain radioactivity which rapidly declined to a much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [11C](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects. PMID:21438532

[11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats.

PubMed

Zessin, Jörg; Deuther-Conrad, Winnie; Kretzschmar, Marion; Wüst, Frank; Pawelke, Beate; Brust, Peter; Steinbach, Jörg; Bergmann, Ralf

2006-01-01

N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [(11)C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value. Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

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.

Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging.

PubMed

Toyota, Yasunori; Miyake, Keisuke; Kawai, Nobuyuki; Hatakeyama, Tetsuhiro; Yamamoto, Yuka; Toyohara, Jun; Nishiyama, Yoshihiro; Tamiya, Takashi

2015-01-01

3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, (18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of (11)C-4DST PET in the diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET. Twenty patients with primary and recurrent brain gliomas underwent (18)F-FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were compared among different glioma grades. Correlation between the Ki-67 labeling index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also examined. (11)C-4DST uptake was significantly higher than that of (18)F-FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT. No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were noted among different glioma grades. Linear regression analysis showed a significant correlation between the Ki-67 labeling index and the T/N ratio of (11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of (11)C-4DST and (18)F-FLT in the tumor (r = 0.79, P = 0.0001). The present study demonstrates that (11)C-4DST is useful for the imaging of human brain gliomas with PET. A relatively higher background uptake of (11)C-4DST in the normal brain compared to (18)F-FLT limits the detection of low-tracer-uptake tumors. Moreover, no superiority was found in (11)C-4DST over (18)F-FLT in the evaluation of cell proliferation.

Chronic Methamphetamine Effects on Brain Structure and Function in Rats

PubMed Central

Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

2016-01-01

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity. PMID:27275601

Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

PubMed

Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

2016-01-01

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity.

PET Studies of CX-157

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

Fowler, Joanna; Furey, Michael

We completed measuring Brain MAO A activity in 15 subjects at baseline and after different doses of CX157 and also at different times after each dose. Fifty five scans were completed. We determined that plasma levels of the drug are a surrogate marker for the degree of MAO A inhibition in the brain.

Evaluation of [11C]metergoline as a PET radiotracer for 5HTR in nonhuman primates

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

Hooker, J.M.; Hooker, J.M.; Kim, S.W.

2010-04-20

Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

PET/CT imaging evidence of FUS-mediated (18)F-FDG uptake changes in rat brain

PubMed Central

Kim, Hyungmin; Park, Mi-Ae; Wang, Shuyan; Chiu, Alan; Fischer, Krisztina; Yoo, Seung-Schik

2013-01-01

Purpose: Transcranial focused ultrasound (FUS) delivers highly focused acoustic energy to a small region of the brain in a noninvasive manner. Recent studies have revealed that FUS, which is administered either in pulsed or continuous waves, can elicit or suppress neural tissue excitability. This neuromodulatory property of FUS has been demonstrated via direct motion detection, electrophysiological recordings, functional magnetic resonance imaging (fMRI), confocal imaging, and microdialysis sampling of neurotransmitters. This study presents new evidence of local increase in glucose metabolism induced by FUS to the rat brain using FDG (18-fludeoxyglucose) positron emission tomography (PET). Methods: Sprague–Dawley rats underwent sonication to a unilateral hemispheric area of the brain prior to PET scan. The pulsed sonication (350 kHz, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, and duration of 300 ms) was applied in 2 s intervals for 40 min immediately after the FDG injection via tail vein. Subsequently, the PET was acquired in dynamic list-mode to image FDG activity for an hour, and reconstructed into a single volume representing standardized uptake value (SUV). The raw SUV as well as its asymmetry index (AI) were measured from five different volume-of-interests (VOIs) of the brain for both hemispheres, and compared between sonicated and unsonicated groups. Results: Statistically significant hemispheric changes in SUV were observed only at the center of sonication focus within the FUS group [paired t-test; t(7) = 3.57, p < 0.05]. There were no significant hemispheric differences in SUV within the control group in any of the VOIs. A statistically significant elevation in AI (t-test; t(7) = 3.40, p < 0.05) was observed at the center of sonication focus (7.9 ± 2.5%, the deviations are in standard error) among the FUS group when compared to the control group (−0.8 ± 1.2%). Conclusions: Spatially distinct increases in the glucose metabolic activity in the rat brain is present only at the center of sonication focus, suggesting localized functional neuromodulation mediated by the sonication. PMID:23464343

Evaluation of drug effects on cerebral blood flow and glucose uptake in un-anesthetized and un-stimulated rats: application of free-moving apparatus enabling to keep rats free during PET/SPECT tracer injection and uptake.

PubMed

Sugita, Taku; Kondo, Yusuke; Ishino, Seigo; Mori, Ikuo; Horiguchi, Takashi; Ogawa, Mikako; Magata, Yasuhiro

2018-05-15

The purpose of this study is the development of novel fluorine-18-fluorodeoxyglucose (F-FDG)-PET and Tc-hexamethylpropylene amine oxime (HMPAO) SPECT methods with free-moving apparatus on conscious rats to investigate brain activity without the effects of anesthesia and tactual stimulation. We also assessed the sensitivity of the experimental system by an intervention study using fluoxetine as a reference drug. A catheter was inserted into the femoral vein and connected to a free-moving cannula system. After fluoxetine administration, the rats were given an injection of F-FDG or Tc-HMPAO via the intravenous cannula and released into a free-moving cage. After the tracer was trapped in the brain, the rats were anesthetized and scanned with PET or SPECT scanners. Then a volume of interest analysis and statistical parametric mapping were performed. We could inject the tracer without touching the rats, while keeping them conscious until the tracers were distributed and trapped in the brain using the developed system. The effects of fluoxetine on glucose uptake and cerebral blood flow were perceptively detected by volume of interest and statistical parametric mapping analysis. We successfully developed free-moving F-FDG-PET and Tc-HMPAO-SPECT imaging systems and detected detailed glucose uptake and cerebral blood flow changes in the conscious rat brain with fluoxetine administration. This system is expected to be useful to assess brain activity without the effects of anesthesia and tactual stimulation to evaluate drug effect or animal brain function.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Specific binding of [(18)F]fluoroethyl-harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain.

PubMed

Maschauer, Simone; Haller, Adelina; Riss, Patrick J; Kuwert, Torsten; Prante, Olaf; Cumming, Paul

2015-12-01

We investigated [(18)F]fluoroethyl-harmol ([(18)F]FEH) as a reversible and selective ligand for positron emission tomography (PET) studies of monoamine oxidase A (MAO-A). Binding of [(18)F]FEH in rat brain cryostat sections indicated high affinity (KD = 3 nM), and density (Bmax; 600 pmol/g). The plasma free fraction was 45%, and untransformed parent constituted only 13% of plasma radioactivity at 10 min after injection. Compartmental analysis of PET recordings in pargyline-treated rats showed high permeability to brain (K1; 0.32 mL/g/min) and slow washout (k2; 0.024/min), resulting in a uniformly high equilibrium distribution volume (VD; 20 mL/g). Using this VD to estimate unbound ligand in brain of untreated rats, the binding potential ranged from 4.2 in cerebellum to 7.2 in thalamus. We also calculated maps of rats receiving [(18)F]FEH at a range of specific activities, and then estimated saturation binding parameters in the living brain. In thalamus, striatum and frontal cortex KD was globally close to 300 nM and Bmax was close to 1600 pmol/g; the 100-fold discrepancy in affinity suggests a very low free fraction for [(18)F]FEH in the living brain. Based on a synthesis of findings, we calculate the endogenous dopamine concentration to be 0.4 μM in the striatal compartment containing MAO-A, thus unlikely to exert competition against [(18)F]FEH binding in vivo. In summary, [(18)F]FEH has good properties for the detection of MAO-A in the rat brain by PET, and may present logistic advantages for clinical research at centers lacking a medical cyclotron. We made a compartmental analysis of [(18)F]fluoroethylharmol ([(18)F]FEH) binding to monoamine oxidase A (MAO-A) in living rat brain and estimated the saturation binding parameters from the binding potential (BPND). The Bmax was of comparable magnitude to that in vitro, but with apparent affinity (300 nM), it was 100-fold lower in vivo. PET imaging with [(18) F]FEH is well suited for quantitation of MAO-A in living brain. © 2015 International Society for Neurochemistry.

Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-¹⁸F-fluoropropyl)pyridine (¹⁸F-Nifrolene) using PET.

PubMed

Pichika, Rama; Kuruvilla, Sharon A; Patel, Narmisha; Vu, Kenny; Sinha, Sangamitra; Easwaramoorthy, Balu; Narayanan, Tanjore K; Shi, Bingzhi; Christian, Bradley; Mukherjee, Jogeshwar

2013-01-01

Imaging agents for nicotinic α4β2 receptors in the brain have been under way for studying various CNS disorders. Previous studies from our laboratories have reported the successful development of agonist, ¹⁸F-nifene. In attempts to develop potential antagonists, ¹⁸F-nifrolidine and ¹⁸F-nifzetidine were previously reported. Further optimization of these fluoropropyl derivatives has now been carried out resulting in 3-(2-(S)-3,4-dehydropyrrolinylmethoxy)-5-(3'-Fluoropropyl)pyridine (nifrolene) as a new high affinity agent for nicotinic α4β2 receptors. Nifrolene in rat brain homogenate assays--labeled with ³H-cytisine--exhibited a binding affinity of 0.36 nM. The fluorine-18 analog, ¹⁸F-nifrolene, was synthesized in approximately 10%-20% yield and specific activity was estimated to be >2000 Ci/mmol. Rat brain slices indicated selective binding to anterior thalamic nuclei, thalamus, subiculum, striata, cortex and other regions consistent with α4β2 receptor distribution. This selective binding was displaced >90% by 300 μM nicotine. Thalamus to cerebellum ratio (>10) was the highest for ¹⁸F-nifrolene with several other regions showing selective binding. In vivo rat PET studies exhibited rapid uptake of ¹⁸F-nifrolene in the brain with specific retention in the thalamus and other brain regions while clearing out from the cerebellum. Thalamus to cerebellum ratio value in the rat was >4. Administration of nicotine caused a rapid decline in the thalamic ¹⁸F-nifrolene suggesting reversible binding to nicotinic receptors. PET imaging studies of ¹⁸F-nifrolene in anesthetized rhesus monkey revealed highest binding in the thalamus followed by regions of the lateral cingulated and temporal cortex. Cerebellum showed the least binding. Thalamus to cerebellum ratio in the monkey brain was >3 at 120 min. These ratios of ¹⁸F-nifrolene are higher than measured for ¹⁸F-nifrolidine and ¹⁸F-nifzetidine. ¹⁸F-Nifrolene thus shows promise as a new PET imaging agent for α4β2 nAChR. Copyright © 2013 Elsevier Inc. All rights reserved.

Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [(11)C]MADAM PET study.

PubMed

Finnema, Sjoerd J; Halldin, Christer; Bang-Andersen, Benny; Bundgaard, Christoffer; Farde, Lars

2015-11-01

A number of serotonin receptor positron emission tomography (PET) radioligands have been shown to be sensitive to changes in extracellular serotonin concentration, in a generalization of the well-known dopamine competition model. High doses of selective serotonin reuptake inhibitors (SSRIs) decrease serotonin receptor availability in monkey brain, consistent with increased serotonin concentrations. However, two recent studies on healthy human subjects, using a single, lower and clinically relevant SSRI dose, showed increased cortical serotonin receptor radioligand binding, suggesting potential decreases in serotonin concentration in projection regions when initiating treatment. The cross-species differential SSRI effect may be partly explained by serotonin transporter (SERT) occupancy in monkey brain being higher than is clinically relevant. We here determine SERT occupancy after single doses of escitalopram or citalopram by conducting PET measurements with [(11)C]MADAM in monkeys. Relationships between dose, plasma concentration and SERT occupancy were estimated by one-site binding analyses. Binding affinity was expressed as dose (ID50) or plasma concentration (K i) where 50 % SERT occupancy was achieved. Estimated ID50 and K i values were 0.020 mg/kg and 9.6 nmol/L for escitalopram and 0.059 mg/kg and 9.7 nmol/L for citalopram, respectively. Obtained K i values are comparable to values reported in humans. Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies which examined serotonin sensitivity of receptor radioligands. PET-measured cross-species differential effects of SSRI on cortical serotonin concentration may thus be related to SSRI dose. Future monkey studies using SSRI doses inducing clinically relevant SERT occupancy may further illuminate the delayed onset of SSRI therapeutic effects.

The use of longitudinal 18F-FET MicroPET imaging to evaluate response to irinotecan in orthotopic human glioblastoma multiforme xenografts.

PubMed

Nedergaard, Mette K; Kristoffersen, Karina; Michaelsen, Signe R; Madsen, Jacob; Poulsen, Hans S; Stockhausen, Marie-Thérése; Lassen, Ulrik; Kjaer, Andreas

2014-01-01

Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared. Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens. The relative tumor-to-brain (T/B) ratio of SUV max was significantly lower after one week (123 ± 6%, n = 7 vs. 147 ± 6%, n = 7; p = 0.018) and after two weeks (142 ± 8%, n = 5 vs. 204 ± 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = -0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts. 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.

Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury: A pilot study.

PubMed

Yoon, Seo Yeon; Lee, Sang Chul; Kim, Na Young; An, Young-Sil; Kim, Yong Wook

2017-11-01

Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET).We consecutively enrolled 11 patients with FOG after HIBI. The patients' overall brain metabolism was measured by F-18 FDG PET, and we compared their regional brain metabolic activity with that from 15 healthy controls using a voxel-by-voxel-based statistical mapping analysis. Additionally, we correlated each patient's FOG severity with the brain metabolism using a covariance analysis.Patients with FOG had significantly decreased brain glucose metabolism in the midbrain, bilateral thalamus, bilateral cingulate gyri, right supramarginal gyrus, right angular gyrus, right paracentral lobule, and left precentral gyrus (PFDR-corrected < .01, k = 50). No significant increases in brain metabolism were noted in patients with FOG. The covariance analysis identified significant correlations between the FOG severity and the brain metabolism in the right lingual gyrus, left fusiform gyrus, and bilateral cerebellar crus I (Puncorrected < 0.001, k = 50).Our data suggest that brain regions in the gait-related neural network, including the cerebral cortex, subcortical structures, brainstem, and cerebellum, may significantly contribute to the development of FOG in HIBI. Moreover, the FOG severity may be associated with the visual cortex and cerebellar regions.

In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma

PubMed Central

Coughlin, J M; Wang, Y; Ambinder, E B; Ward, R E; Minn, I; Vranesic, M; Kim, P K; Ford, C N; Higgs, C; Hayes, L N; Schretlen, D J; Dannals, R F; Kassiou, M; Sawa, A; Pomper, M G

2016-01-01

Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [11C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [11C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease. PMID:27070405

Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment.

PubMed

Verger, Antoine; Stoffels, Gabriele; Galldiks, Norbert; Lohmann, Philipp; Willuweit, Antje; Neumaier, Bernd; Geisler, Stefanie; Langen, Karl-Josef

2018-04-23

Cis-4-[ 18 F]fluoro-D-proline (D-cis-[ 18 F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[ 18 F]FPro in human brain tumors after multimodal treatment. In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[ 18 F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBR mean , LBR max ), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n = 9), clinical follow-up (n = 10), or by [ 18 F]FET PET (n = 10). D-cis-[ 18 F]FPro showed high uptake in both recurrent brain tumors (n = 11) and lesions classified as treatment-related changes (TRC) only (n = 16) (LBR mean 2.2 ± 0.7 and 2.1 ± 0.6, n.s.; LBR max 3.4 ± 1.2 and 3.2 ± 1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[ 18 F]FPro uptake. Distribution of [ 18 F]FET and D-cis-[ 18 F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different. The high accumulation of D-cis-[ 18 F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[ 18 F]FPro for treatment monitoring.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.

PubMed

Barrio, Jorge R; Small, Gary W; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A; Giza, Christopher C; Fitzsimmons, Robert P; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

2015-04-21

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

PubMed Central

Barrio, Jorge R.; Small, Gary W.; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A.; Giza, Christopher C.; Fitzsimmons, Robert P.; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

2015-01-01

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. PMID:25848027

PET Studies in Nonhuman Primate Models of Cocaine Abuse: Translational Research Related to Vulnerability and Neuroadaptations

PubMed Central

Gould, Robert W.; Duke, Angela N.; Nader, Michael A.

2013-01-01

The current review highlights the utility of positron emission tomography (PET) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self-administration in nonhuman primate models of cocaine abuse. Environmental (e.g., social rank) and sex-specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed. Cocaine-related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models. Lastly, the long-term consequences of cocaine on neurobiology are discussed. PET imaging and longitudinal, within-subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug-dependent treatment seekers. Non-invasive PET imaging will allow for individualized treatment strategies. Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain. PMID:23458573

99mTc-MDM Brain SPECT for the Detection of Recurrent/Remnant Glioma-Comparison With ceMRI and 18F-FLT PET Imaging: Initial Results.

PubMed

Singh, Baljinder; Kumar, Narendra; Sharma, Sarika; Watts, Ankit; Hazari, Puja P; Rani, Nisha; Vyas, Sameer; Anish, Bhattacharya; Mishra, Anil K

2015-10-01

To evaluate the diagnostic use of an indigenously developed single vial ready to label (with Tc) kit preparation of bis-methionine-DTPA (Tc-MDM) for the detection of recurrent/residual glioma. We prospectively studied 32 patients (21 male and 11 female subjects aged 43.0±16.0 years) with clinical suspicion of postoperative recurrent/residual glioma. After radical radiotherapy (54.0-60.0 Gy) with or without concurrent temozolomide as indicated, Tc-MDM SPECT and ceMRI of the brain was performed in all the patients and F-FLT-PET imaging in 16 of 32 patients. MDM SPECT and ceMRI findings were concordant in 28 patients (15 positive and 13 negative). The findings were discordant in the remaining 5 patients, with positive ceMRI and negative MDM-SPECT in 2 patients and negative ceMRI and positive MDM-SPECT in 3 patients. Tc-MDM-SPECT, F-FLT PET, and ceMRI scan findings were positive in 9 of 16 and negative in 5 of 16 patients. In the remaining 2 of 16 patients, both F-FLT-PET and Tc-MDM-SPECT were positive, but ceMRI was negative. Sensitivity, specificity, PPV, NPV, and DA of Tc-MDM-SPECT for diagnosing recurrent/residual glioma were 88.24%, 81.25%, 83.3%, 86.7%, and 84.8%, respectively. The diagnostic accuracy of Tc-bis-methionine (MDM)-SPECT imaging was comparable with that of ceMRI and F-FLT-PET and may be useful in the management of glioma patients in the postsurgical follow-up period. This imaging technique may be of special interest in peripheral hospitals/developing countries lacking access to expensive PET/cyclotron technology. However, comparison with the existing "gold standard" PET tracers, especially with C-11-methionine-PET imaging and histopathological correlation, is warranted in a large cohort of glioma patients through multicentric studies.

Resting functional imaging tools (MRS, SPECT, PET and PCT).

PubMed

Van Der Naalt, J

2015-01-01

Functional imaging includes imaging techniques that provide information about the metabolic and hemodynamic status of the brain. Most commonly applied functional imaging techniques in patients with traumatic brain injury (TBI) include magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), positron emission tomography (PET) and perfusion CT (PCT). These imaging modalities are used to determine the extent of injury, to provide information for the prediction of outcome, and to assess evidence of cerebral ischemia. In TBI, secondary brain damage mainly comprises ischemia and is present in more than 80% of fatal cases with traumatic brain injury (Graham et al., 1989; Bouma et al., 1991; Coles et al., 2004). In particular, while SPECT measures cerebral perfusion and MRS determines metabolism, PET is able to assess both perfusion and cerebral metabolism. This chapter will describe the application of these techniques in traumatic brain injury separately for the major groups of severity comprising the mild and moderate to severe group. The application in TBI and potential difficulties of each technique is described. The use of imaging techniques in children will be separately outlined. © 2015 Elsevier B.V. All rights reserved.

Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

PubMed

Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

2016-01-01

Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM.

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.

Development of a 3D Brain PET Scanner Using CdTe Semiconductor Detectors and Its First Clinical Application

NASA Astrophysics Data System (ADS)

Morimoto, Y.; Ueno, Y.; Takeuchi, W.; Kojima, S.; Matsuzaki, K.; Ishitsu, T.; Umegaki, K.; Kiyanagi, Y.; Kubo, N.; Katoh, C.; Shiga, T.; Shirato, H.; Tamaki, N.

2011-10-01

Targeting improved spatial resolution, a three-dimensional positron-emission-tomography (PET) scanner employing CdTe semiconductor detectors and using depth-of-interaction (DOI) information was developed, and its physical performance was evaluated. This PET scanner is the first to use semiconductor detectors dedicated to the human brain and head-and-neck region. Imaging performance of the scanner used for 18F -fluorodeoxy glucose (FDG) scans of phantoms and human brains was evaluated. The gantry of the scanner has a 35.0-cm-diameter patient port, the trans-axial field of view (FOV) is 31.0 cm, and the axial FOV is 24.6 cm. The energy resolution averaged over all detector channels and timing resolution were 4.1% and 6.8 ns (each in FWHM), respectively. Spatial resolution measured at the center of FOV was 2.3-mm FWHM-which is one of the best resolutions achieved by human PET scanners. Noise-equivalent count ratio (NEC2R) has a maximum in the energy window of 390 to 540 keV and is 36 kcps/Bq/cm3 at 3.7 kBq/cm3 . The sensitivity of the system according to NEMA 1994 was 25.9 cps/Bq/cm3. Scatter fraction of the scanner is 37% for the energy window of 390 to 540 keV and 23% for 450 to 540 keV. Images of a hot-rod phantom and images of brain glucose metabolism show that the structural accuracy of the images obtained with the semiconductor PET scanner is higher than that possible with a conventional Bismuth Germanium Oxide (BGO) PET scanner. In addition, the developed scanner permits better delineation of the head-and-neck cancer. These results show that the semiconductor PET scanner will play a major role in the upcoming era of personalized medicine.

Concept of an upright wearable positron emission tomography imager in humans.

PubMed

Bauer, Christopher E; Brefczynski-Lewis, Julie; Marano, Gary; Mandich, Mary-Beth; Stolin, Alexander; Martone, Peter; Lewis, James W; Jaliparthi, Gangadhar; Raylman, Raymond R; Majewski, Stan

2016-09-01

Positron Emission Tomography (PET) is traditionally used to image patients in restrictive positions, with few devices allowing for upright, brain-dedicated imaging. Our team has explored the concept of wearable PET imagers which could provide functional brain imaging of freely moving subjects. To test feasibility and determine future considerations for development, we built a rudimentary proof-of-concept prototype (Helmet_PET) and conducted tests in phantoms and four human volunteers. Twelve Silicon Photomultiplier-based detectors were assembled in a ring with exterior weight support and an interior mechanism that could be adjustably fitted to the head. We conducted brain phantom tests as well as scanned four patients scheduled for diagnostic F(18-) FDG PET/CT imaging. For human subjects the imager was angled such that field of view included basal ganglia and visual cortex to test for typical resting-state pattern. Imaging in two subjects was performed ~4 hr after PET/CT imaging to simulate lower injected F(18-) FDG dose by taking advantage of the natural radioactive decay of the tracer (F(18) half-life of 110 min), with an estimated imaging dosage of 25% of the standard. We found that imaging with a simple lightweight ring of detectors was feasible using a fraction of the standard radioligand dose. Activity levels in the human participants were quantitatively similar to standard PET in a set of anatomical ROIs. Typical resting-state brain pattern activation was demonstrated even in a 1 min scan of active head rotation. To our knowledge, this is the first demonstration of imaging a human subject with a novel wearable PET imager that moves with robust head movements. We discuss potential research and clinical applications that will drive the design of a fully functional device. Designs will need to consider trade-offs between a low weight device with high mobility and a heavier device with greater sensitivity and larger field of view.

FDG-PET imaging in mild traumatic brain injury: a critical review

PubMed Central

Byrnes, Kimberly R.; Wilson, Colin M.; Brabazon, Fiona; von Leden, Ramona; Jurgens, Jennifer S.; Oakes, Terrence R.; Selwyn, Reed G.

2013-01-01

Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States and is a contributing factor to one third of all injury related deaths annually. According to the CDC, approximately 75% of all reported TBIs are concussions or considered mild in form, although the number of unreported mild TBIs (mTBI) and patients not seeking medical attention is unknown. Currently, classification of mTBI or concussion is a clinical assessment since diagnostic imaging is typically inconclusive due to subtle, obscure, or absent changes in anatomical or physiological parameters measured using standard magnetic resonance (MR) or computed tomography (CT) imaging protocols. Molecular imaging techniques that examine functional processes within the brain, such as measurement of glucose uptake and metabolism using [18F]fluorodeoxyglucose and positron emission tomography (FDG-PET), have the ability to detect changes after mTBI. Recent technological improvements in the resolution of PET systems, the integration of PET with magnetic resonance imaging (MRI), and the availability of normal healthy human databases and commercial image analysis software contribute to the growing use of molecular imaging in basic science research and advances in clinical imaging. This review will discuss the technological considerations and limitations of FDG-PET, including differentiation between glucose uptake and glucose metabolism and the significance of these measurements. In addition, the current state of FDG-PET imaging in assessing mTBI in clinical and preclinical research will be considered. Finally, this review will provide insight into potential critical data elements and recommended standardization to improve the application of FDG-PET to mTBI research and clinical practice. PMID:24409143

Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies

PubMed Central

Tong, Junchao; Meyer, Jeffrey H; Furukawa, Yoshiaki; Boileau, Isabelle; Chang, Li-Jan; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J

2013-01-01

Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [11C]harmine, [11C]clorgyline, and [11C]befloxatone; MAO-B: [11C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n=38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [11C]befloxatone (binding potential (BP), r=0.61, P=0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P<0.01) for [11C]harmine (distribution volume, r=0.86), [11C]clorgyline (λk3, r=0.82), and [11C]deprenyl-D2 (λk3 or modified Patlak slope, r=0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ∼2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality. PMID:23403377

Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.

PubMed

Yang, Yanping; Wang, Xuedan; Yang, Hui; Fu, Hualong; Zhang, Jinming; Zhang, Xiaojun; Dai, Jiapei; Zhang, Zhiyong; Lin, Chunping; Guo, Yuzhi; Cui, Mengchao

2016-11-07

This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)- 18 F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with K i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[ 18 F]28 possessed high binding potency (K i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain 2min /brain 60min = 27.8) that is superior to well-established [ 18 F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[ 18 F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[ 18 F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[ 18 F]28 to detect Aβ plaques with high signal-to-noise ratio.

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.

Simultaneous MRI and PET imaging of a rat brain

NASA Astrophysics Data System (ADS)

Raylman, Raymond R.; Majewski, Stan; Lemieux, Susan K.; Sendhil Velan, S.; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Zorn, Carl; Marano, Gary D.

2006-12-01

Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

Optimization of PET instrumentation for brain activation studies

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

Dahlbom, M.; Cherry, S.R.; Hoffman, E.J.

By performing cerebral blood flow studies with positron emission tomography (PET), and comparing blood flow images of different states of activation, functional mapping of the brain is possible. The ability of current commercial instruments to perform such studies is investigated in this work, based on a comparison of noise equivalent count (NEC) rates. Differences in the NEC performance of the different scanners in conjunction with scanner design parameters, provide insights into the importance of block design (size, dead time, crystal thickness) and overall scanner design (sensitivity and scatter fraction) for optimizing data from activation studies. The newer scanners with removablemore » septa, operating with 3-D acquisition, have much higher sensitivity, but require new methodology for optimized operation. Only by administering multiple low doses (fractionation) of the flow tracer can the high sensitivity be utilized.« less

Radioisotope generators for short-lived positron emitters applicable to positron emission tomography

NASA Astrophysics Data System (ADS)

Yano, Y.

1989-04-01

Radioisotope generators provide short-lived positron emitters for positron emission tomography (PET) without the need for an on-site cyclotron. These generators consist of a long-lived parent radionuclide, generally produced on an accelerator, from which the short-lived daughter radionuclide is separated and used as needed. Generators developed and applied to PET studies include 288 d 68Ge for 68 min 68Ga, 25 d 82Sr for 76 s 82Rb and 20.1 h 122Xe for 3.6 min 122I. These radiotracers have been used for the assessment of myocardial and brain blood flow in patient studies. Additionally, 82Rb has been used to determine the breakdown in the blood brain barrier in brain tumor patients who have undergone radiation therapy. When used in conjunction with 18F-fluorodeoxylucose produced on a regional cyclotron for the measurement of glucose utilization in brain tumors, differential diagnosis can be made between tumor regrowth and radiation therapy necrosis. Other possible applications include the detection of vascular lesions with 68Ga labeled platelets or porphyrins.

PET imaging and quantitation of Internet-addicted patients and normal controls

NASA Astrophysics Data System (ADS)

Jeong, Ha-Kyu; Kim, Hee-Joung; Jung, Haijo; Son, Hye-Kyung; Kim, Dong-Hyeon; Yun, Mijin; Shin, Yee-Jin; Lee, Jong-Doo

2002-04-01

Internet addicted patients (IAPs) have widely been increased, as Internet games are becoming very popular in daily life. The purpose of this study was to investigate regional brain activation patterns associated with excessive use of Internet games in adolescents. Six normal controls (NCs) and eight IAPs who were classified as addiction group by adapted version of DSM-IV for pathologic gambling were participated. 18F-FDG PET studies were performed for all adolescents at their rest and activated condition after 20 minutes of each subject's favorite Internet game. To investigate quantitative metabolic differences in both groups, all possible combinations of group comparison were carried out using Statistical Parametric Mapping (SPM 99). Regional brain activation foci were identified on Talairach coordinate. SPM results showed increased metabolic activation in occipital lobes for both groups. Higher metabolisms were seen at resting condition in IAPs than that of in NCs. In comparison to both groups, IAPs showed different patterns of regional brain metabolic activation compared with that of NCs. It suggests that addictive use of Internet games may result in functional alteration of developing brain in adolescents.

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer

PubMed Central

Cuaron, John; Dunphy, Mark; Rimner, Andreas

2013-01-01

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET. PMID:23316478

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer.

PubMed

Cuaron, John; Dunphy, Mark; Rimner, Andreas

2012-01-01

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated (18)F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. (18)F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. (18)F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on (18)F-FDG-PET scan when CT criteria for malignant involvement are not met. (18)F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. (18)F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. (18)F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3-6 months, using (18)F-FDG-PET to evaluate equivocal CT findings. As high (18)F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, (18)F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable (18)F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.

Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

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

Knapp, F.F. Jr.; McPherson, D.W.; Luo, H.

1995-06-01

Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development ofmore » the new iodinated IQNP ligand based on QNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the {open_quotes}partial{close_quotes} subtype selective IONP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.« less

Development of a circular shape Si-PM-based detector ring for breast-dedicated PET system

NASA Astrophysics Data System (ADS)

Nakanishi, Kouhei; Yamamoto, Seiichi; Watabe, Hiroshi; Abe, Shinji; Fujita, Naotoshi; Kato, Katsuhiko

2018-02-01

In clinical situations, various breast-dedicated positron emission tomography (PET) systems have been used. However, clinical breast-dedicated PET systems have polygonal detector ring. Polygonal detector ring sometimes causes image artifact, so complicated reconstruction algorithm is needed to reduce artifact. Consequently, we developed a circular detector ring for breast-dedicated PET to obtain images without artifact using a simple reconstruction algorithm. We used Lu1.9Gd0.1SiO5 (LGSO) scintillator block which was made of 1.5 x 1.9 x 15 mm pixels that were arranged in an 8 x 24 matrix. As photodetectors, we used silicon photomultiplier (Si-PM) arrays whose channel size was 3 x 3 mm. A detector unit was composed of four scintillator blocks, 16 Si-PM arrays and a light guide. The developed detector unit had angled configuration since the light guide was bending. A detector unit had three gaps with an angle of 5.625° between scintillator blocks. With these configurations, we could arrange 64 scintillator blocks in nearly circular shape (regular 64-sided polygon) using 16 detector units. The use of the smaller number of detector units could reduce the size of the front-end electronics circuits. The inner diameter of the developed detector ring was 260 mm. This size was similar to those of brain PET systems, so our breast-dedicated PET detector ring can measure not only breast but also brain. Measured radial, tangential and axial spatial resolution of the detector ring reconstructed by the filtered back-projection (FBP) algorithm were 2.1 mm FWHM, 2.0 mm FWHM and 1.7 mm FWHM at center of field of view (FOV), respectively. The sensitivity was 2.0% at center of the axial FOV. With the developed detector ring, we could obtain high resolution image of the breast phantom and the brain phantom. We conclude that our developed Si-PM-based detector ring is promising for a high resolution breast-dedicated PET system that can also be used for brain PET system.

Application of positron emission tomography to neuroimaging in sports sciences.

PubMed

Tashiro, Manabu; Itoh, Masatoshi; Fujimoto, Toshihiko; Masud, Md Mehedi; Watanuki, Shoichi; Yanai, Kazuhiko

2008-08-01

To investigate exercise-induced regional metabolic and perfusion changes in the human brain, various methods are available, such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS) and electroencephalography (EEG). In this paper, details of methods of metabolic measurement using PET, [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(15)O]radio-labelled water ([(15)O]H(2)O) will be explained. Functional neuroimaging in the field of neuroscience was started in the 1970s using an autoradiography technique on experimental animals. The first human functional neuroimaging exercise study was conducted in 1987 using a rough measurement system known as (133)Xe inhalation. Although the data was useful, more detailed and exact functional neuroimaging, especially with respect to spatial resolution, was achieved by positron emission tomography. Early studies measured the cerebral blood flow changes during exercise. Recently, PET was made more applicable to exercise physiology and psychology by the use of the tracer [(18)F]FDG. This technique allowed subjects to be scanned after an exercise task is completed but still obtain data from the exercise itself, which is similar to autoradiography studies. In this report, methodological information is provided with respect to the recommended protocol design, the selection of the scanning mode, how to evaluate the cerebral glucose metabolism and how to interpret the regional brain activity using voxel-by-voxel analysis and regions of interest techniques (ROI). Considering the important role of exercise in health promotion, further efforts in this line of research should be encouraged in order to better understand health behavior. Although the number of research papers is still limited, recent work has indicated that the [(18)F]FDG-PET technique is a useful tool to understand brain activity during exercise.

Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

PubMed

Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

2013-04-01

Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

Positron emission tomography reveals correlations between brain metabolism and mood changes in hyperthyroidism.

PubMed

Schreckenberger, M F; Egle, U T; Drecker, S; Buchholz, H G; Weber, M M; Bartenstein, P; Kahaly, G J

2006-12-01

Hyperthyroidism is frequently associated with emotional distress. The underlying cerebral processes of the endocrine-induced mood changes are unclear. The objective of this study was to investigate, for the first time, the neuronal correlates of thyrotoxicosis-associated psychic symptoms using positron emission tomography (PET). The study was designed as a cross-sectional trial. The study was performed at joint nuclear medicine and thyroid clinics. Twelve patients with untreated Graves' hyperthyroidism were evaluated. Levels of emotional distress were self-rated by means of the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender-matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan. Subsequently, the functional relationship between brain metabolism and the psychometric scores was analyzed. Compared with controls and visualized by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001) glucose metabolism in the limbic system (uncus and inferior temporal gyrus). Activation foci in the posterior cingulate and in the inferior parietal lobe were correlated with both anxiety and depression scales (P < 0.001). Compared with patients with normal anxiety levels, those with increased anxiety yielded an enhanced glucose metabolism (P < 0.001) in the bilateral sensory association cortex. Serum free T3/free T4 levels negatively correlated with regional glucose metabolism in the medial posterior cingulate. Thyrotoxicosis and associated psychic symptoms are correlated to regional metabolic changes in the main structures of the limbic/paralimbic system.

GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP.

PubMed

Ramanan, Vijay K; Risacher, Shannon L; Nho, Kwangsik; Kim, Sungeun; Shen, Li; McDonald, Brenna C; Yoder, Karmen K; Hutchins, Gary D; West, John D; Tallman, Eileen F; Gao, Sujuan; Foroud, Tatiana M; Farlow, Martin R; De Jager, Philip L; Bennett, David A; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford R; Toga, Arthur W; Green, Robert C; Jagust, William J; Weiner, Michael W; Saykin, Andrew J

2015-10-01

Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.

PubMed

Staley, J K; Van Dyck, C H; Tan, P Z; Al Tikriti, M; Ramsby, Q; Klump, H; Ng, C; Garg, P; Soufer, R; Baldwin, R M; Innis, R B

2001-04-01

The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.

Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI

NASA Astrophysics Data System (ADS)

Harsha Maramraju, Sri; Smith, S. David; Junnarkar, Sachin S.; Schulz, Daniela; Stoll, Sean; Ravindranath, Bosky; Purschke, Martin L.; Rescia, Sergio; Southekal, Sudeepti; Pratte, Jean-François; Vaska, Paul; Woody, Craig L.; Schlyer, David J.

2011-04-01

We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm3) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [11C]raclopride and 2-deoxy-2-[18F]fluoro-d-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.

Functional brain imaging and bioacoustics in the Bottlenose dolphins, Tursiops truncatus

NASA Astrophysics Data System (ADS)

Ridgway, Sam; Finneran, James; Carder, Donald; van Bonn, William; Smith, Cynthia; Houser, Dorian; Mattrey, Robert; Hoh, Carl

2003-10-01

The dolphin brain is the central processing computer for a complex and effective underwater echolocation and communication system. Until now, it has not been possible to study or diagnose disorders of the dolphin brain employing modern functional imaging methods like those used in human medicine. Our most recent studies employ established methods such as behavioral tasks, physiological observations, and computed tomography (CT) and, for the first time, single photon emission computed tomography (SPECT), and positron emission tomography (PET). Trained dolphins slide out of their enclosure on to a mat and are transported by trainers and veterinarians to the laboratory for injection of a ligand. Following ligand injection, brief experiments include trained vocal responses to acoustic, visual, or tactile stimuli. We have used the ligand technetium (Tc-99m) biscisate (Neurolite) to image circulatory flow by SPECT. Fluro-deoxy-d-glucose (18-F-FDG) has been employed to image brain metabolism with PET. Veterinarians carefully monitored dolphins during and after the procedure. Through these methods, we have demonstrated that functional imaging can be employed safely and productively with dolphins to obtain valuable information on brain structure and function for medical and research purposes. Hemispheric differences and variations in flow and metabolism in different brain areas will be shown.

Radionecrosis versus disease progression in brain metastasis. Value of (18)F-DOPA PET/CT/MRI.

PubMed

Hernández Pinzón, J; Mena, D; Aguilar, M; Biafore, F; Recondo, G; Bastianello, M

2016-01-01

The use of (18)F-DOPA PET/CT with magnetic resonance imaging fusion and the use of visual methods and quantitative analysis helps to differentiate between changes post-radiosurgery vs. suspicion of disease progression in a patient with brain metastases from melanoma, thus facilitating taking early surgical action. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI.

PubMed

Stegger, Lars; Martirosian, Petros; Schwenzer, Nina; Bisdas, Sotirios; Kolb, Armin; Pfannenberg, Christina; Claussen, Claus D; Pichler, Bernd; Schick, Fritz; Boss, Andreas

2012-11-01

Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear. To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device. ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 × 128 and 192 × 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors. Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51 ± 9 and 51 ± 7 mL/100 g/min for the 128 × 128 and 192 × 192 matrices (stand-alone MR, 57 ± 2 and 55 ± 5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 × 192 matrix size (P < 0.01), the relative signal change (δS) was significantly lower for the 192 × 192 matrix size (P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality. ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.

Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

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

Maass, Anne; Landau, Susan; Baker, Suzanne L.

The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current paper was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ +) patients with mild cognitive impairment (MCI) or AD-dementia underwent [ 18F]AV-1451more » PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ - controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Finally, our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.« less

Maturation of metabolic connectivity of the adolescent rat brain

PubMed Central

Choi, Hongyoon; Choi, Yoori; Kim, Kyu Wan; Kang, Hyejin; Hwang, Do Won; Kim, E Edmund; Chung, June-Key; Lee, Dong Soo

2015-01-01

Neuroimaging has been used to examine developmental changes of the brain. While PET studies revealed maturation-related changes, maturation of metabolic connectivity of the brain is not yet understood. Here, we show that rat brain metabolism is reconfigured to achieve long-distance connections with higher energy efficiency during maturation. Metabolism increased in anterior cerebrum and decreased in thalamus and cerebellum during maturation. When functional covariance patterns of PET images were examined, metabolic networks including default mode network (DMN) were extracted. Connectivity increased between the anterior and posterior parts of DMN and sensory-motor cortices during maturation. Energy efficiency, a ratio of connectivity strength to metabolism of a region, increased in medial prefrontal and retrosplenial cortices. Our data revealed that metabolic networks mature to increase metabolic connections and establish its efficiency between large-scale spatial components from childhood to early adulthood. Neurodevelopmental diseases might be understood by abnormal reconfiguration of metabolic connectivity and efficiency. DOI: http://dx.doi.org/10.7554/eLife.11571.001 PMID:26613413

Equilibrium modeling of 5-HT(2A) receptors with [18F]deuteroaltanserin and PET: feasibility of a constant infusion paradigm.

PubMed

van Dyck, C H; Soares, J C; Tan, P Z; Staley, J K; Baldwin, R M; Amici, L A; Fu, X; Garg, P K; Seibyl, J P; Charney, D S; Innis, R B

2000-11-01

[(18)F]Altanserin has emerged as a promising positron emission tomography (PET) ligand for serotonin-2A (5-HT(2A)) receptors. The deuterium substitution of both of the 2'-hydrogens of altanserin ([(18)F]deuteroaltanserin) yields a metabolically more stable radiotracer with higher ratios of parent tracer to radiometabolites and increased specific brain uptake than [(18)F]altanserin. The slower metabolism of the deuterated analog might preclude the possibility of achieving stable plasma and brain activities with a bolus plus constant infusion within a reasonable time frame for an (18)F-labeled tracer (T(1/2) 110 min). Thus, the purpose of this study was to test the feasibility in human subjects of a constant infusion paradigm for equilibrium modeling of [(18)F]deuteroaltanserin with PET. Seven healthy male subjects were injected with [(18)F]deuteroaltanserin as a bolus plus constant infusion lasting 10 h postinjection. PET acquisitions and venous blood sampling were performed throughout the infusion period. Linear regression analysis revealed that time-activity curves for both specific brain uptake and plasma [(18)F]deuteroaltanserin concentration stabilized after about 5 h. This permitted equilibrium modeling and estimation of V(')(3) (ratio of specific uptake to total plasma parent concentration) and the binding potential V(3) (ratio of specific uptake to free plasma parent concentration). Cortical/cerebellar ratios were increased by 26% relative to those we previously observed with [(18)F]altanserin using similar methodology in a somewhat older subject sample. These results demonstrate feasibility of equilibrium imaging with [(18)F]deuteroaltanserin and suggest that it may be superior to [(18)F]altanserin as a PET radioligand.

FDG-PET reproducibility in tumor-bearing mice: comparing a traditional SUV approach with a tumor-to-brain tissue ratio approach.

PubMed

Busk, Morten; Munk, Ole L; Jakobsen, Steen; Frøkiær, Jørgen; Overgaard, Jens; Horsman, Michael R

2017-05-01

Current [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) procedures in tumor-bearing mice typically includes fasting, anesthesia, and standardized uptake value (SUV)-based quantification. Such procedures may be inappropriate for prolonged multiscan experiments. We hypothesize that normalization of tumor FDG retention relative to a suitable reference tissue may improve accuracy as this method may be less susceptible to uncontrollable day-to-day changes in blood glucose levels, physical activity, or unnoticed imperfect tail vein injections. Fed non-anesthetized tumor-bearing mice were administered FDG intravenously (i.v.) or intraperitoneally (i.p.) and PET scanned on consecutive days using a Mediso nanoScan PET/magnetic resonance imaging (MRI). Reproducibility of various PET-deduced measures of tumor FDG retention, including normalization to FDG signal in reference organs and a conventional SUV approach, was evaluated. Day-to-day variability in i.v. injected mice was lower when tumor FDG retention was normalized to brain signal (T/B), compared to normalization to other tissues or when using SUV-based normalization. Assessment of tissue radioactivity in dissected tissues confirmed the validity of PET-derived T/B ratios. Mean T/B and SUV values were similar in i.v. and i.p. administered animals, but SUV normalization was more robust in the i.p. group than in the i.v. group. Multimodality scanners allow tissue delineation and normalization of tumor FDG uptake relative to reference tissues. Normalization to brain, but not liver or kidney, improved scan reproducibility considerably and was superior to traditional SUV quantification in i.v. tracer-injected animals. Day-to-day variability in SUV's was lower in i.p. than in i.v. injected animals, and i.p. injections may therefore be a valuable alternative in prolonged rodent studies, where repeated vein injections are undesirable.

Lean body mass correction of standardized uptake value in simultaneous whole-body positron emission tomography and magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Jochimsen, Thies H.; Schulz, Jessica; Busse, Harald; Werner, Peter; Schaudinn, Alexander; Zeisig, Vilia; Kurch, Lars; Seese, Anita; Barthel, Henryk; Sattler, Bernhard; Sabri, Osama

2015-06-01

This study explores the possibility of using simultaneous positron emission tomography—magnetic resonance imaging (PET-MRI) to estimate the lean body mass (LBM) in order to obtain a standardized uptake value (SUV) which is less dependent on the patients' adiposity. This approach is compared to (1) the commonly-used method based on a predictive equation for LBM, and (2) to using an LBM derived from PET-CT data. It is hypothesized that an MRI-based correction of SUV provides a robust method due to the high soft-tissue contrast of MRI. A straightforward approach to calculate an MRI-derived LBM is presented. It is based on the fat and water images computed from the two-point Dixon MRI primarily used for attenuation correction in PET-MRI. From these images, a water fraction was obtained for each voxel. Averaging over the whole body yielded the weight-normalized LBM. Performance of the new approach in terms of reducing variations of 18F-Fludeoxyglucose SUVs in brain and liver across 19 subjects was compared with results using predictive methods and PET-CT data to estimate the LBM. The MRI-based method reduced the coefficient of variation of SUVs in the brain by 41  ± 10% which is comparable to the reduction by the PET-CT method (35  ± 10%). The reduction of the predictive LBM method was 29  ± 8%. In the liver, the reduction was less clear, presumably due to other sources of variation. In conclusion, employing the Dixon data in simultaneous PET-MRI for calculation of lean body mass provides a brain SUV which is less dependent on patient adiposity. The reduced dependency is comparable to that obtained by CT and predictive equations. Therefore, it is more comparable across patients. The technique does not impose an overhead in measurement time and is straightforward to implement.

Lean body mass correction of standardized uptake value in simultaneous whole-body positron emission tomography and magnetic resonance imaging.

PubMed

Jochimsen, Thies H; Schulz, Jessica; Busse, Harald; Werner, Peter; Schaudinn, Alexander; Zeisig, Vilia; Kurch, Lars; Seese, Anita; Barthel, Henryk; Sattler, Bernhard; Sabri, Osama

2015-06-21

This study explores the possibility of using simultaneous positron emission tomography--magnetic resonance imaging (PET-MRI) to estimate the lean body mass (LBM) in order to obtain a standardized uptake value (SUV) which is less dependent on the patients' adiposity. This approach is compared to (1) the commonly-used method based on a predictive equation for LBM, and (2) to using an LBM derived from PET-CT data. It is hypothesized that an MRI-based correction of SUV provides a robust method due to the high soft-tissue contrast of MRI. A straightforward approach to calculate an MRI-derived LBM is presented. It is based on the fat and water images computed from the two-point Dixon MRI primarily used for attenuation correction in PET-MRI. From these images, a water fraction was obtained for each voxel. Averaging over the whole body yielded the weight-normalized LBM. Performance of the new approach in terms of reducing variations of (18)F-Fludeoxyglucose SUVs in brain and liver across 19 subjects was compared with results using predictive methods and PET-CT data to estimate the LBM. The MRI-based method reduced the coefficient of variation of SUVs in the brain by 41 ± 10% which is comparable to the reduction by the PET-CT method (35 ± 10%). The reduction of the predictive LBM method was 29 ± 8%. In the liver, the reduction was less clear, presumably due to other sources of variation. In conclusion, employing the Dixon data in simultaneous PET-MRI for calculation of lean body mass provides a brain SUV which is less dependent on patient adiposity. The reduced dependency is comparable to that obtained by CT and predictive equations. Therefore, it is more comparable across patients. The technique does not impose an overhead in measurement time and is straightforward to implement.

The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

PubMed

Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

2015-01-01

Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve cerebral metabolism around the hematoma by attenuating apoptotic cell death after ICH. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Designing a compact high performance brain PET scanner—simulation study

NASA Astrophysics Data System (ADS)

Gong, Kuang; Majewski, Stan; Kinahan, Paul E.; Harrison, Robert L.; Elston, Brian F.; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V.; Brefczynski-Lewis, Julie A.; Qi, Jinyi

2016-05-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér-Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of-interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging.

Designing a compact high performance brain PET scanner—simulation study

PubMed Central

Gong, Kuang; Majewski, Stan; Kinahan, Paul E; Harrison, Robert L; Elston, Brian F; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V; Brefczynski-Lewis, Julie A; Qi, Jinyi

2016-01-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér–Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of- interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging. PMID:27081753

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

PubMed

Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally administered labelled CNS drugs in the living human body.

[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging.

PubMed

Marquié, Marta; Siao Tick Chong, Michael; Antón-Fernández, Alejandro; Verwer, Eline E; Sáez-Calveras, Nil; Meltzer, Avery C; Ramanan, Prianca; Amaral, Ana C; Gonzalez, Jose; Normandin, Marc D; Frosch, Matthew P; Gómez-Isla, Teresa

2017-10-01

[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I-II, n = 6), intermediate Braak (III-IV, n = 7) and high Braak (V-VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging-pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations.

Impairment of nonverbal recognition in Alzheimer disease: a PET O-15 study.

PubMed

Anderson, K E; Brickman, A M; Flynn, J; Scarmeas, N; Van Heertum, R; Sackeim, H; Marder, K S; Bell, K; Moeller, J R; Stern, Y

2007-07-03

To characterize deficits in nonverbal recognition memory and functional brain changes associated with these deficits in Alzheimer disease (AD). Using O-15 PET, we studied 11 patients with AD and 17 cognitively intact elders during the combined encoding and retrieval periods of a nonverbal recognition task. Both task conditions involved recognition of line drawings of abstract shapes. In both conditions, subjects were first presented a list of shapes as study items, and then a list as test items, containing items from the study list and foils. In the titrated demand condition, the shape study list size (SLS) was adjusted prior to imaging so that each subject performed at approximately 75% recognition accuracy; difficulty during PET scanning in this condition was approximately matched across subjects. A control task was used in which SLS = 1 shape. During performance of the titrated demand condition, SLS averaged 4.55 (+/-1.86) shapes for patients with AD and 7.53 (+/-4.81) for healthy elderly subjects (p = 0.031). However, both groups of subjects were closely matched on performance in the titrated demand condition during PET scanning with 72.17% (+/-7.98%) correct for patients with AD and 72.25% (+/-7.03%) for elders (p = 0.979). PET results demonstrated that patients with AD showed greater mean differences between the titrated demand condition and control in areas including the left fusiform and inferior frontal regions (Brodmann areas 19 and 45). Relative fusiform and inferior frontal differences may reflect the Alzheimer disease (AD) patients' compensatory engagement of alternate brain regions. The strategy used by patients with AD is likely to be a general mechanism of compensation, rather than task-specific.

(11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists.

PubMed

Van Laere, Koenraad J; Sanabria-Bohórquez, Sandra M; Mozley, David P; Burns, Donald H; Hamill, Terence G; Van Hecken, Anne; De Lepeleire, Inge; Koole, Michel; Bormans, Guy; de Hoon, Jan; Depré, Marleen; Cerchio, Kristine; Plalcza, John; Han, Lingling; Renger, John; Hargreaves, Richard J; Iannone, Robert

2014-01-01

The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity. Using PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level. The mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses. (11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

PET/CT in giant cell arteritis: High 18F-FDG uptake in the temporal, occipital and vertebral arteries.

PubMed

Rehak, Z; Vasina, J; Ptacek, J; Kazda, T; Fojtik, Z; Nemec, P

18 F-FDG PET/CT imaging is useful in patients with fever of unknown origin and can detect giant cell arteritis in extracranial large arteries. However, it is usually assumed that temporal arteries cannot be visualized with a PET/CT scanner due to their small diameter. Three patients with clinical symptoms of temporal arteritis were examined using a standard whole body PET/CT protocol (skull base - mid thighs) followed by a head PET/CT scan using the brain protocol. High 18 F-FDG uptake in the aorta and some arterial branches were detected in all 3 patients with the whole body protocol. Using the brain protocol, head imaging led to detection of high 18 F-FDG uptake in temporal arteries as well as in their branches (3 patients), in occipital arteries (2 patients) and also in vertebral arteries (3 patients). Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Probing neurodegeneration and aging: A PET approach

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

VanBrocklin, H.F.

1995-12-31

Positron Emission Tomography (PET) imaging has received wide application to the study of the aging brain and its diseases, most notably Parkinson`s Disease (PD) and Alzheimer`s Disease (AD). Basic neurological processes such as blood flow and glucose metabolism have been most often measured. Radioligands developed for specific neurochemical systems have amplified the flow and metabolism studies by more precisely defining the changes associated with degenerative processes. Our present research focuses on two additional applications of radiopharmaceutical development and PET imaging - (1) investigating the fundamental mechanisms of neurodegeneration and aging, and (2) assessing novel therapeutic intervention for PD with PETmore » imaging. We have synthesized fluorine-18 labeled analogs of rotenone, a natural product that possesses high affinity to Complex I of the mitochondrial electron transport chain, and evaluated their potential to study changes in neuronal mitochondrial density and function. A large body evidence points to mitochondrial dysfunction as a key factor in aging and neurodegeneration. We are also currently evaluating the use of genetically transfected cells to treat PD. Primates are being imaged with [{sup 18}F]flouro-m-L-tyrosine before and after MPTP Parkinsonian type lesioning and following implantation of genetically altered cells capable of secreting tyrosine hydroxylase into the lesioned area. The ability to develop and apply PET probes has significantly enhanced the understanding of normal, aging, and degenerative processes of the brain.« less

Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

PubMed

Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

2016-01-01

The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (P<0.01) were found in the NSCLC patients (n = 83). The hypermetabolism regions (bilateral insula, putamen, pallidum, thalamus, hippocampus and amygdala, the right side of cerebellum, orbital part of right inferior frontal gyrus and vermis) were component parts of visceral to brain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

Towards quantitative [18F]FDG-PET/MRI of the brain: Automated MR-driven calculation of an image-derived input function for the non-invasive determination of cerebral glucose metabolic rates.

PubMed

Sundar, Lalith Ks; Muzik, Otto; Rischka, Lucas; Hahn, Andreas; Rausch, Ivo; Lanzenberger, Rupert; Hienert, Marius; Klebermass, Eva-Maria; Füchsel, Frank-Günther; Hacker, Marcus; Pilz, Magdalena; Pataraia, Ekaterina; Traub-Weidinger, Tatjana; Beyer, Thomas

2018-01-01

Absolute quantification of PET brain imaging requires the measurement of an arterial input function (AIF), typically obtained invasively via an arterial cannulation. We present an approach to automatically calculate an image-derived input function (IDIF) and cerebral metabolic rates of glucose (CMRGlc) from the [18F]FDG PET data using an integrated PET/MRI system. Ten healthy controls underwent test-retest dynamic [18F]FDG-PET/MRI examinations. The imaging protocol consisted of a 60-min PET list-mode acquisition together with a time-of-flight MR angiography scan for segmenting the carotid arteries and intermittent MR navigators to monitor subject movement. AIFs were collected as the reference standard. Attenuation correction was performed using a separate low-dose CT scan. Assessment of the percentage difference between area-under-the-curve of IDIF and AIF yielded values within ±5%. Similar test-retest variability was seen between AIFs (9 ± 8) % and the IDIFs (9 ± 7) %. Absolute percentage difference between CMRGlc values obtained from AIF and IDIF across all examinations and selected brain regions was 3.2% (interquartile range: (2.4-4.3) %, maximum < 10%). High test-retest intravariability was observed between CMRGlc values obtained from AIF (14%) and IDIF (17%). The proposed approach provides an IDIF, which can be effectively used in lieu of AIF.

Three dimensional image correlation of CT, MR, and PET studies in radiotherapy treatment planning of brain tumors.

PubMed

Schad, L R; Boesecke, R; Schlegel, W; Hartmann, G H; Sturm, V; Strauss, L G; Lorenz, W J

1987-01-01

A treatment planning system for stereotactic convergent beam irradiation of deeply localized brain tumors is reported. The treatment technique consists of several moving field irradiations in noncoplanar planes at a linear accelerator facility. Using collimated narrow beams, a high concentration of dose within small volumes with a dose gradient of 10-15%/mm was obtained. The dose calculation was based on geometrical information of multiplanar CT or magnetic resonance (MR) imaging data. The patient's head was fixed in a stereotactic localization system, which is usable at CT, MR, and positron emission tomography (PET) installations. Special computer programs for correction of the geometrical MR distortions allowed a precise correlation of the different imaging modalities. The therapist can use combinations of CT, MR, and PET data for defining target volume. For instance, the superior soft tissue contrast of MR coupled with the metabolic features of PET may be a useful addition in the radiation treatment planning process. Furthermore, other features such as calculated dose distribution to critical structures can also be transferred from one set of imaging data to another and can be displayed as three-dimensional shaded structures.

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer's Disease.

PubMed

Fantoni, Enrico R; Chalkidou, Anastasia; O' Brien, John T; Farrar, Gill; Hammers, Alexander

2018-01-01

Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis). Data was abstracted by consensus among two observers and assessed for bias. Clinical utility was measured by diagnostic change, diagnostic confidence, and patient management before and after aPET. Three groups were further analyzed: control patients for whom feedback of aPET scan results was delayed; aPET Appropriate Use Criteria (AUC+) cases; and patients undergoing additional FDG/CSF testing. For 1,142 cases with only aPET, 31.3% of diagnoses were revised, whereas 3.2% of diagnoses changed in the delayed aPET control group (p < 0.0001). Increased diagnostic confidence following aPET was found for 62.1% of 870 patients. Management changes with aPET were found in 72.2% of 740 cases and in 55.5% of 299 cases in the control group (p < 0.0001). The diagnostic value of aPET in AUC+ patients or when FDG/CSF were additionally available did not substantially differ from the value of aPET alone in the wider population. Amyloid PET contributed to diagnostic revision in almost a third of cases and demonstrated value in increasing diagnostic confidence and refining management plans.

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer’s Disease

PubMed Central

Fantoni, Enrico R.; Chalkidou, Anastasia; O’ Brien, John T.; Farrar, Gill; Hammers, Alexander

2018-01-01

Background: Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. Objective: To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. Methods: Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis). Data was abstracted by consensus among two observers and assessed for bias. Clinical utility was measured by diagnostic change, diagnostic confidence, and patient management before and after aPET. Three groups were further analyzed: control patients for whom feedback of aPET scan results was delayed; aPET Appropriate Use Criteria (AUC+) cases; and patients undergoing additional FDG/CSF testing. Results: For 1,142 cases with only aPET, 31.3% of diagnoses were revised, whereas 3.2% of diagnoses changed in the delayed aPET control group (p < 0.0001). Increased diagnostic confidence following aPET was found for 62.1% of 870 patients. Management changes with aPET were found in 72.2% of 740 cases and in 55.5% of 299 cases in the control group (p < 0.0001). The diagnostic value of aPET in AUC+ patients or when FDG/CSF were additionally available did not substantially differ from the value of aPET alone in the wider population. Conclusions: Amyloid PET contributed to diagnostic revision in almost a third of cases and demonstrated value in increasing diagnostic confidence and refining management plans. PMID:29689725

Assessment of 10B concentration in boron neutron capture therapy: potential of image-guided therapy using 18FBPA PET.

PubMed

Shimosegawa, Eku; Isohashi, Kayako; Naka, Sadahiro; Horitsugi, Genki; Hatazawa, Jun

2016-12-01

In boron neutron capture therapy (BNCT) for cancer, the accurate estimation of 10 B tissue concentrations, especially in neighboring normal organs, is important to avoid adverse effects. The 10 B concentration in normal organs after loading with 10 B, however, has not been established in humans. In this study, we performed 4-borono-2-[ 18 F]-fluoro-phenylalanine ( 18 FBPA) PET in healthy volunteers and estimated the chronological changes in the 10 B concentrations of normal organs. In 6 healthy volunteers, whole-body 18 FBPA PET scans were repeated 7 times during 1 h, and the mean 18 FBPA distributions of 13 organs were measured. Based on the 18 FBPA PET data, we then estimated the changes in the 10 B concentrations of the organs when the injection of a therapeutic dose of 10 BPA-fructose complex ( 10 BPA-fr; 30 g, 500 mg/kg body weight) was assumed. The maximum mean 18 FBPA concentrations were reached at 2-6 min after injection in all the organs except the brain and urinary bladder. The mean 18 FBPA concentration in normal brain plateaued at 24 min after injection. When the injection of a therapeutic dose of 10 BPA-fr was assumed, the estimated mean 10 B concentration in the kidney increased to 126.1 ± 24.2 ppm at 3 min after injection and then rapidly decreased to 30.9 ± 7.4 ppm at 53 min. The estimated mean 10 B concentration in the bladder gradually increased and reached 383.6 ± 214.7 ppm at 51 min. The mean 10 B concentration in the brain was estimated to be 7.6 ± 1.5 ppm at 57 min. 18 FBPA PET has a potential to estimate 10 B concentration of normal organs before neutron irradiation of BNCT when several assumptions are validated in the future studies.

Neuropsychological and FDG-PET profiles in VGKC autoimmune limbic encephalitis.

PubMed

Dodich, Alessandra; Cerami, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Alongi, Pierpaolo; Crespi, Chiara; Canessa, Nicola; Andreetta, Francesca; Falini, Andrea; Cappa, Stefano F; Perani, Daniela

2016-10-01

Limbic encephalitis (LE) is characterized by an acute or subacute onset with memory impairments, confusional state, behavioral disorders, variably associated with seizures and dystonic movements. It is due to inflammatory processes that selectively affect the medial temporal lobe structures. Voltage-gate potassium channel (VGKC) autoantibodies are frequently observed. In this study, we assessed at the individual level FDG-PET brain metabolic dysfunctions and neuropsychological profiles in three autoimmune LE cases seropositive for neuronal VGKC-complex autoantibodies. LGI1 and CASPR2 potassium channel complex autoantibody subtyping was performed. Cognitive abilities were evaluated with an in-depth neuropsychological battery focused on episodic memory and affective recognition/processing skills. FDG-PET data were analyzed at single-subject level according to a standardized and validated voxel-based Statistical Parametric Mapping (SPM) method. Patients showed severe episodic memory and fear recognition deficits at the neuropsychological assessment. No disorder of mentalizing processing was present. Variable patterns of increases and decreases of brain glucose metabolism emerged in the limbic structures, highlighting the pathology-driven selective vulnerability of this system. Additional involvement of cortical and subcortical regions, particularly in the sensorimotor system and basal ganglia, was found. Episodic memory and fear recognition deficits characterize the cognitive profile of LE. Commonalities and differences may occur in the brain metabolic patterns. Single-subject voxel-based analysis of FDG-PET imaging could be useful in the early detection of the metabolic correlates of cognitive and non-cognitive deficits characterizing LE condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Study of amyloid-β peptide functional brain networks in AD, MCI and HC.

PubMed

Jiang, Jiehui; Duan, Huoqiang; Huang, Zheming; Yu, Zhihua

2015-01-01

One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD.

Use of FDG-PET to detect a chronic odontogenic infection as a possible source of the brain abscess.

PubMed

Sato, Jun; Kuroshima, Takeshi; Wada, Mayumi; Satoh, Akira; Watanabe, Shiro; Okamoto, Shozo; Shiga, Tohru; Tamaki, Nagara; Kitagawa, Yoshimasa

2016-05-01

This study describes the use of (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to detect a chronic odontogenic infection as the possible origin of a brain abscess (BA). A 74-year-old man with esophageal carcinoma was referred to our department to determine the origin of a BA in his oral cavity. He had no acute odontogenic infections. The BA was drained, and bacteria of the Staphylococcus milleri group were detected. Whole body FDG-PET revealed that the only sites of definite uptake of FDG were the esophageal carcinoma and the left upper maxillary region (SUVmax: 4.5). These findings suggested that the BA may have originated from a chronic periodontal infection. Six teeth with progressive chronic periodontal disease were extracted to remove the possible source of BA. These findings excluded the possibility of direct spread of bacteria from the odontogenic infectious lesion to the intracranial cavity. After extraction, there was no relapse of BA.

Gender Differences of Brain Glucose Metabolic Networks Revealed by FDG-PET: Evidence from a Large Cohort of 400 Young Adults

PubMed Central

Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Background Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. Materials and Methods FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Results Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. Conclusion This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients. PMID:24358312

Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

PubMed

Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

Rationale for Activity Based Alternatives in Lieu of Lectures. Research Brief

ERIC Educational Resources Information Center

Walker, Karen

2005-01-01

Since the 1990s was declared to be the decade of the brain, technology has advanced enough through MRIs, CAT Scans and PET Scans, that live brains have been able to be studied. Although this is still a relatively new field of study, what has been discovered thus far, has wide reaching implications for educators in the area of pedagogy and how to…

Improving the convergence rate in affine registration of PET and SPECT brain images using histogram equalization.

PubMed

Salas-Gonzalez, D; Górriz, J M; Ramírez, J; Padilla, P; Illán, I A

2013-01-01

A procedure to improve the convergence rate for affine registration methods of medical brain images when the images differ greatly from the template is presented. The methodology is based on a histogram matching of the source images with respect to the reference brain template before proceeding with the affine registration. The preprocessed source brain images are spatially normalized to a template using a general affine model with 12 parameters. A sum of squared differences between the source images and the template is considered as objective function, and a Gauss-Newton optimization algorithm is used to find the minimum of the cost function. Using histogram equalization as a preprocessing step improves the convergence rate in the affine registration algorithm of brain images as we show in this work using SPECT and PET brain images.

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.

Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

NASA Astrophysics Data System (ADS)

Asselin, Marie-Claude; Cunningham, Vincent J.; Amano, Shigeko; Gunn, Roger N.; Nahmias, Claude

2004-03-01

A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[18F]fluoro-L-DOPA and one subject injected with [11C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest.

PET imaging in ischemic cerebrovascular disease: current status and future directions.

PubMed

Heiss, Wolf-Dieter

2014-10-01

Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases.

Molecular Imaging of ABCB1 and ABCG2 Inhibition at the Human Blood-Brain Barrier Using Elacridar and 11C-Erlotinib PET.

PubMed

Verheijen, Remy B; Yaqub, Maqsood; Sawicki, Emilia; van Tellingen, Olaf; Lammertsma, Adriaan A; Nuijen, Bastiaan; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R; Hendrikse, N Harry; Steeghs, Neeltje

2018-06-01

Transporters such as ABCB1 and ABCG2 limit the exposure of several anticancer drugs to the brain, leading to suboptimal treatment in the central nervous system. The purpose of this study was to investigate the effects of the ABCB1 and ABCG2 inhibitor elacridar on brain uptake using 11 C-erlotinib PET. Methods: Elacridar and cold erlotinib were administered orally to wild-type (WT) and Abcb1a/b;Abcg2 knockout mice. In addition, brain uptake was measured using 11 C-erlotinib imaging and ex vivo scintillation counting in knockout and WT mice. Six patients with advanced solid tumors underwent 11 C-erlotinib PET scans before and after a 1,000-mg dose of elacridar. 11 C-erlotinib brain uptake was quantified by pharmacokinetic modeling using volume of distribution (V T ) as the outcome parameter. In addition, 15 O-H 2 O scans to measure cerebral blood flow were acquired before each 11 C-erlotinib scan. Results: Brain uptake of 11 C-erlotinib was 2.6-fold higher in Abcb1a/b;Abcg2 knockout mice than in WT mice, measured as percentage injected dose per gram of tissue ( P = 0.01). In WT mice, the addition of elacridar (at systemic plasma concentrations of ≥200 ng/mL) resulted in an increased brain concentration of erlotinib, without affecting erlotinib plasma concentration. In patients, the V T of 11 C-erlotinib did not increase after intake of elacridar (0.213 ± 0.12 vs. 0.205 ± 0.07, P = 0.91). 15 O-H 2 O PET showed no significant changes in cerebral blood flow. Elacridar exposure in patients was 401 ± 154 ng/mL. No increase in V T with increased elacridar plasma exposure was found over the 271-619 ng/mL range. Conclusion: When Abcb1 and Abcg2 were disrupted in mice, brain uptake of 11 C-erlotinib increased both at a tracer dose and at a pharmacologic dose. In patients, brain uptake of 11 C-erlotinib was not higher after administration of elacridar. The more pronounced role that ABCG2 appears to play at the human blood-brain barrier and the lower potency of elacridar to inhibit ABCG2 may be an explanation of these interspecies differences. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

The history of cerebral PET scanning

PubMed Central

Portnow, Leah H.; Vaillancourt, David E.; Okun, Michael S.

2013-01-01

Objective: To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Background: Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post–World War II period provided the necessary infrastructure for the first cerebral PET scan. Methods: A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at www.sfn.org. A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. Results: The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Conclusions: Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders. PMID:23460618

The history of cerebral PET scanning: from physiology to cutting-edge technology.

PubMed

Portnow, Leah H; Vaillancourt, David E; Okun, Michael S

2013-03-05

To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post-World War II period provided the necessary infrastructure for the first cerebral PET scan. A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at www.sfn.org. A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders.

Visualisation of brain tumors and quantitation of the protein synthesis rate with L-1-[C-11]-tyrosine

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

Pruim, J.; Willemsen, A.T.M.; Waarde, A. van

1994-05-01

We have developed the tracer L-1-[C-11]-tyrosine (TYR) for the quantitation of the protein synthesis rate (PSR) in tumours. Here the first results with TYR in a group of patients with (suspected) primary or recurrent brain tumours are reported. Twenty-six patients were studied: 12 male, 14 female, age 45{plus_minus}16 (mean{plus_minus}S.D.) years. At the time of the study the diagnosis of a primary tumour or recurrent tumour was considered on the basis of clinical symptoms and CT/MRI. Patients received 237{plus_minus}111 MBq TYR i.v. Seventeen patients were studied in a dynamic mode (frame sequence: 10 x 0.5, 3 x 5, 3 x 10more » minutes). During the studies, arterial blood samples were taken for measurement of the input function, and the assessment of metabolites ([C-11]CO{sub 2}, [C-11]proteins). ROIs were placed over the tumour and using a modified Patlak-analysis the PSR was calculated. In the other 9 patients a static emission scan was made, 20-40 min after injection. All images were corrected for attenuation via a transmission scan. Histology or cytology of the tumour was obtained shortly after the TYR-PET in 20 patients. The calculated PSR of the tumours was 1.0{plus_minus}0.6 nmol/ml/min. This is in range with our animal experiments. The PSR in brain tissue of the contralateral hemisphere was 0.7{plus_minus}0.4 nmol/ml/min. Sixteen of the turnouts were correctly identified with TYR-PET. Also, 2 benign lesions were correctly identified. TYR-PET gave 1 false-positive (infarction) and 1 false-negative (astrocytoma of intermediate malignancy) result. In a few patients with extensive peri-tumoural edema on MRI/CT, additional tumour locations were found with TYR-PET, proven to be malignant on biopsy. In conclusion: TYR is applicable for the visualisation of brain tumours. The possibility of calculating a PSR allows its use in the evaluation of therapy.« less

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

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

Small-worldness and gender differences of large scale brain metabolic covariance networks in young adults: a FDG PET study of 400 subjects.

PubMed

Hu, Yuxiao; Xu, Qiang; Shen, Junkang; Li, Kai; Zhu, Hong; Zhang, Zhiqiang; Lu, Guangming

2015-02-01

Many studies have demonstrated the small-worldness of the human brain, and have revealed a sexual dimorphism in brain network properties. However, little is known about the gender effects on the topological organization of the brain metabolic covariance networks. To investigate the small-worldness and the gender differences in the topological architectures of human brain metabolic networks. FDG-PET data of 400 healthy right-handed subjects (200 women and 200 age-matched men) were involved in the present study. Metabolic networks of each gender were constructed by calculating the covariance of regional cerebral glucose metabolism (rCMglc) across subjects on the basis of AAL parcellation. Gender differences of network and nodal properties were investigated by using the graph theoretical approaches. Moreover, the gender-related difference of rCMglc in each brain region was tested for investigating the relationships between the hub regions and the brain regions showing significant gender-related differences in rCMglc. We found prominent small-world properties in the domain of metabolic networks in each gender. No significant gender difference in the global characteristics was found. Gender differences of nodal characteristic were observed in a few brain regions. We also found bilateral and lateralized distributions of network hubs in the females and males. Furthermore, we first reported that some hubs of a gender located in the brain regions showing weaker rCMglc in this gender than the other gender. The present study demonstrated that small-worldness was existed in metabolic networks, and revealed gender differences of organizational patterns in metabolic network. These results maybe provided insights into the understanding of the metabolic substrates underlying individual differences in cognition and behaviors. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Composite PET and MRI for accurate localization and metabolic modeling: a very useful tool for research and clinic

NASA Astrophysics Data System (ADS)

Bidaut, Luc M.

1991-06-01

In order to help in analyzing PET data and really take advantage of their metabolic content, a system was designed and implemented to align and process data from various medical imaging modalities, particularly (but not only) for brain studies. Although this system is for now mostly used for anatomical localization, multi-modality ROIs and pharmaco-kinetic modeling, more multi-modality protocols will be implemented in the future, not only to help in PET reconstruction data correction and semi-automated ROI definition, but also for helping in improving diagnostic accuracy along with surgery and therapy planning.

Positron Emission Tomography and Neuropathologic Estimates of Fibrillar Amyloid-β in a Patient With Down Syndrome and Alzheimer Disease

PubMed Central

Sabbagh, Marwan N.; Fleisher, Adam; Chen, Kewei; Rogers, Joseph; Berk, Camryn; Reiman, Eric; Pontecorvo, Michael; Mintun, Mark; Skovronsky, Daniel; Jacobson, Sandra A.; Sue, Lucia I.; Liebsack, Carolyn; Charney, Albert S.; Cole, Lauren; Belden, Christine; Beach, Thomas G.

2012-01-01

Background Down syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined. Objectives To characterize PET estimates of fibrillar Aβ burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death. Design/Methods With the family’s informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient’s diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient’s diagnosis or PET measurements. Results Visual ratings and automated analyses of the PET image revealed a heavy fibrillar Aβ burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late-onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan. Conclusions Florbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Aβ burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Aβ and to evaluate investigational Aβ-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease. PMID:22084131

PET Imaging of Tau Deposition in the Aging Human Brain

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

Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.

Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. In this study, using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline inmore » global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. In conclusion, the present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.« less

PET Imaging of Tau Deposition in the Aging Human Brain

DOE PAGES

Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.; ...

2016-03-02

Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. In this study, using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline inmore » global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. In conclusion, the present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.« less

Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men.

PubMed

Shumay, Elena; Logan, Jean; Volkow, Nora D; Fowler, Joanna S

2012-10-01

Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters-revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAO A levels (using PET and [(11)C]clorgyline, a radiotracer with specificity for MAO A) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAO A activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAO A levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior.

Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAOA enzyme in healthy men

PubMed Central

Shumay, Elena; Logan, Jean; Volkow, Nora D.; Fowler, Joanna S.

2012-01-01

Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAOA)—an enzyme metabolizing neurotransmitters—revealed that MAOA levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAOA levels (using PET and [11C]clorgyline, a radiotracer with specificity for MAOA) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAOA activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAOA levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior. PMID:22948232

Regional cerebral glucose metabolic abnormality in Prader-Willi syndrome: A 18F-FDG PET study under sedation.

PubMed

Kim, Sang Eun; Jin, Dong-Kyu; Cho, Sang Soo; Kim, Ji-Hae; Hong, Sungdo David; Paik, Kyung Hoon; Oh, Yoo Joung; Kim, An Hee; Kwon, Eun Kyung; Choe, Yon Ho

2006-07-01

Prader-Willi syndrome (PWS) is a genetic disorder caused by the nonexpression of paternal genes in the PWS region of chromosome 15q11-13 and is the most common cause of human syndromic obesity. We investigated regional brain metabolic impairment in children with PWS by 18F-FDG PET. Sixteen children with PWS (9 males, 7 females; mean age +/- SD, 4.2 +/- 1.1 y) and 7 healthy children (4 males, 3 females; mean age +/- SD, 4.0 +/- 1.7 y) underwent brain 18F-FDG PET in the resting state. The images of PWS children were compared using statistical parametric mapping analysis with those of healthy children in a voxelwise manner. Group comparison showed that children with PWS had decreased glucose metabolism in the right superior temporal gyrus and left cerebellar vermis, regions that are associated with taste perception/food reward and cognitive and emotional function, respectively. Metabolism was increased in the right orbitofrontal, bilateral middle frontal, right inferior frontal, left superior frontal, and bilateral anterior cingulate gyri, right temporal pole, and left uncus, regions that are involved in cognitive functions related to eating or obsessive-compulsive behavior. Interestingly, no significant metabolic abnormality was found in the hypothalamus, the brain region believed to be most involved in energy intake and expenditure. This study describes the neural substrate underlying the abnormal eating behavior and psychobehavioral problems of PWS.

Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

PubMed

Perneczky, R; Drzezga, A; Diehl-Schmid, J; Schmid, G; Wohlschläger, A; Kars, S; Grimmer, T; Wagenpfeil, S; Monsch, A; Kurz, A

2006-09-01

Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

Anatomy assisted PET image reconstruction incorporating multi-resolution joint entropy

NASA Astrophysics Data System (ADS)

Tang, Jing; Rahmim, Arman

2015-01-01

A promising approach in PET image reconstruction is to incorporate high resolution anatomical information (measured from MR or CT) taking the anato-functional similarity measures such as mutual information or joint entropy (JE) as the prior. These similarity measures only classify voxels based on intensity values, while neglecting structural spatial information. In this work, we developed an anatomy-assisted maximum a posteriori (MAP) reconstruction algorithm wherein the JE measure is supplied by spatial information generated using wavelet multi-resolution analysis. The proposed wavelet-based JE (WJE) MAP algorithm involves calculation of derivatives of the subband JE measures with respect to individual PET image voxel intensities, which we have shown can be computed very similarly to how the inverse wavelet transform is implemented. We performed a simulation study with the BrainWeb phantom creating PET data corresponding to different noise levels. Realistically simulated T1-weighted MR images provided by BrainWeb modeling were applied in the anatomy-assisted reconstruction with the WJE-MAP algorithm and the intensity-only JE-MAP algorithm. Quantitative analysis showed that the WJE-MAP algorithm performed similarly to the JE-MAP algorithm at low noise level in the gray matter (GM) and white matter (WM) regions in terms of noise versus bias tradeoff. When noise increased to medium level in the simulated data, the WJE-MAP algorithm started to surpass the JE-MAP algorithm in the GM region, which is less uniform with smaller isolated structures compared to the WM region. In the high noise level simulation, the WJE-MAP algorithm presented clear improvement over the JE-MAP algorithm in both the GM and WM regions. In addition to the simulation study, we applied the reconstruction algorithms to real patient studies involving DPA-173 PET data and Florbetapir PET data with corresponding T1-MPRAGE MRI images. Compared to the intensity-only JE-MAP algorithm, the WJE-MAP algorithm resulted in comparable regional mean values to those from the maximum likelihood algorithm while reducing noise. Achieving robust performance in various noise-level simulation and patient studies, the WJE-MAP algorithm demonstrates its potential in clinical quantitative PET imaging.

Modifiable Risk Factors and Brain Positron Emission Tomography Measures of Amyloid and Tau in Nondemented Adults with Memory Complaints.

PubMed

Merrill, David A; Siddarth, Prabha; Raji, Cyrus A; Emerson, Natacha D; Rueda, Florangel; Ercoli, Linda M; Miller, Karen J; Lavretsky, Helen; Harris, Laurel M; Burggren, Alison C; Bookheimer, Susan Y; Barrio, Jorge R; Small, Gary W

2016-09-01

Exercise and diet impact body composition, but their age-related brain effects are unclear at the molecular imaging level. To address these issues, the authors determined whether body mass index (BMI), physical activity, and diet relate to brain positron emission tomography (PET) of amyloid plaques and tau tangles using 2-(1-(6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP). Volunteers (N = 44; mean age: 62.6 ± 10.7 years) with subjective memory impairment (N = 24) or mild cognitive impairment (MCI; N = 20) were recruited by soliciting for memory complaints. Levels of physical activity and extent of following a Mediterranean-type diet were self-reported. FDDNP-PET scans assessed plaque/tangle binding in Alzheimer disease-associated regions (frontal, parietal, medial and lateral temporal, posterior cingulate). Mixed models controlling for known covariates examined BMI, physical activity, and diet in relation to FDDNP-PET. MCI subjects with above normal BMI (>25) had higher FDDNP-PET binding compared with those with normal BMI (1.11(0.03) versus 1.08(0.03), ES = 1.04, t(35) = 3.3, p = 0.002). Greater physical activity was associated with lower FDDNP-PET binding in MCI subjects (1.07(0.03) versus 1.11(0.03), ES = 1.13, t(35) = -3.1, p = 0.004) but not in subjects with subjective memory impairment (1.07(0.03) versus 1.07(0.03), ES = 0.02, t(35) = -0.1, p = 0.9). Healthier diet related to lower FDDNP-PET binding, regardless of cognitive status (1.07(0.03) versus 1.09(0.02), ES = 0.72, t(35) = -2.1, p = 0.04). These preliminary findings are consistent with a relationship between risk modifiersand brain plaque/tangle deposition in nondemented individuals and supports maintenance of normal body weight, regular physical activity, and healthy diet to protect the brain during aging. (clinicaltrials.gov; NCT00355498). Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

ASSOCIATION BETWEEN GAB2 HAPLOTYPE AND HIGHER GLUCOSE METABOLISM IN ALZHEIMER'S DISEASE-AFFECTED BRAIN REGIONS IN COGNITIVELY NORMAL APOEε4 CARRIERS

PubMed Central

Liang, Winnie S.; Chen, Kewei; Lee, Wendy; Sidhar, Kunal; Corneveaux, Jason J.; Allen, April N.; Myers, Amanda; Villa, Stephen; Meechoovet, Bessie; Pruzin, Jeremy; Bandy, Daniel; Fleisher, Adam S.; Langbaum, Jessica B.S.; Huentelman, Matthew J.; Jensen, Kendall; Dunckley, Travis; Caselli, Richard J.; Kaib, Susan; Reiman, Eric M.

2010-01-01

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ε4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative presymptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOEε4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOEε4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk. PMID:20888920

PET image reconstruction using multi-parametric anato-functional priors

NASA Astrophysics Data System (ADS)

Mehranian, Abolfazl; Belzunce, Martin A.; Niccolini, Flavia; Politis, Marios; Prieto, Claudia; Turkheimer, Federico; Hammers, Alexander; Reader, Andrew J.

2017-08-01

In this study, we investigate the application of multi-parametric anato-functional (MR-PET) priors for the maximum a posteriori (MAP) reconstruction of brain PET data in order to address the limitations of the conventional anatomical priors in the presence of PET-MR mismatches. In addition to partial volume correction benefits, the suitability of these priors for reconstruction of low-count PET data is also introduced and demonstrated, comparing to standard maximum-likelihood (ML) reconstruction of high-count data. The conventional local Tikhonov and total variation (TV) priors and current state-of-the-art anatomical priors including the Kaipio, non-local Tikhonov prior with Bowsher and Gaussian similarity kernels are investigated and presented in a unified framework. The Gaussian kernels are calculated using both voxel- and patch-based feature vectors. To cope with PET and MR mismatches, the Bowsher and Gaussian priors are extended to multi-parametric priors. In addition, we propose a modified joint Burg entropy prior that by definition exploits all parametric information in the MAP reconstruction of PET data. The performance of the priors was extensively evaluated using 3D simulations and two clinical brain datasets of [18F]florbetaben and [18F]FDG radiotracers. For simulations, several anato-functional mismatches were intentionally introduced between the PET and MR images, and furthermore, for the FDG clinical dataset, two PET-unique active tumours were embedded in the PET data. Our simulation results showed that the joint Burg entropy prior far outperformed the conventional anatomical priors in terms of preserving PET unique lesions, while still reconstructing functional boundaries with corresponding MR boundaries. In addition, the multi-parametric extension of the Gaussian and Bowsher priors led to enhanced preservation of edge and PET unique features and also an improved bias-variance performance. In agreement with the simulation results, the clinical results also showed that the Gaussian prior with voxel-based feature vectors, the Bowsher and the joint Burg entropy priors were the best performing priors. However, for the FDG dataset with simulated tumours, the TV and proposed priors were capable of preserving the PET-unique tumours. Finally, an important outcome was the demonstration that the MAP reconstruction of a low-count FDG PET dataset using the proposed joint entropy prior can lead to comparable image quality to a conventional ML reconstruction with up to 5 times more counts. In conclusion, multi-parametric anato-functional priors provide a solution to address the pitfalls of the conventional priors and are therefore likely to increase the diagnostic confidence in MR-guided PET image reconstructions.

Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with 18F- fluorodeoxy-glucose PET imaging in the Athymic Nude Rat

NASA Astrophysics Data System (ADS)

Varghai, Davood; Cross, Nathan; Spring-Robinson, Chandra; Sharma, Rahul; Feyes, Denise K.; Ahmad, Yusra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

2007-02-01

Introduction: We have previously demonstrated the use of phthalocyanine Pc 4 for the photodynamic therapy (PDT) of ectopic human glial tumors in the athymic nude rat brain. We wish to determine whether 18F-fluorodeoxy-glucose ( 18F-FDG) Positron Emission Tomography (PET) imaging can detect the reduction in tumor metabolism that must occur after Pc 4-PDT-induced necrosis. Methods: 2.5 x 10 5 U87 cells were injected into the brains of 12 athymic nude rats. After 7 days of tumor growth, all 12 animals were imaged functionally by 18F-FDG micro-PET (μPET) and structurally by micro-CT and/or micro-MR. These animals received 0.5 mg/kg b.w. Pc 4 via tail-vein injection. One day later the scalp was re-incised and the tumor illuminated with 30 J/cm2 of 672-nm light from a diode laser. The next day these animals were again 18F-FDG μPET imaged. Next, the animals were euthanized and their brains were explanted for H&E histology. Results: Histology showed that tumors in the 6 Pc 4-PDT-treated animals demonstrated necrosis ranging from full to frank (severe). Preliminary analysis showed that 18F-FDG μPET activity in 3 of the 6 non-PDT group (i.e., no tumor necrosis observed) animals was seen to increase 2.28 times following tumor photoirradiation, whereas 18F-FDG μPET activity in 5 of the 6 PDT group (i.e., tumor necrosis observed) animals was seen to increase 1.15 times following tumor photoirradiation. Discussion: The increased 18F-FDG μPET activity in the PDT group was unexpected. We had expected this activity to decrease and are presently investigating the cause of this observation.

Brain metabolism in patients with vegetative state after post-resuscitated hypoxic-ischemic brain injury: statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography.

PubMed

Kim, Yong Wook; Kim, Hyoung Seop; An, Young-sil

2013-03-01

Hypoxic-ischemic brain injury (HIBI) after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies investigated the changes of brain metabolism in patients with vegetative state (VS) after post-resuscitated HIBI. This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness (LOC) in patients with VS after post-resuscitated HIBI. We consecutively enrolled 17 patients with VS after HIBI, who experienced cardiopulmonary resuscitation. Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) and we compared regional brain metabolic patterns from 17 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis. Additionally, we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis. Compared with normal controls, the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus, bilateral posterior cingulate gyrus, bilateral middle frontal gyri, bilateral superior parietal gyri, bilateral middle occipital gyri, bilateral precentral gyri (PFEW correctecd < 0.0001), and increased brain metabolism in bilateral insula, bilateral cerebella, and the brainstem (PFEW correctecd < 0.0001). In covariance analysis, the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri (Puncorrected < 0.005). Our study demonstrated that the precuneus, the posterior cingulate area and the frontoparietal cortex, which is a component of neural correlate for consciousness, may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI. In post-resuscitated HIBI, measurement of brain metabolism using PET images may be helpful for investigating the brain function that cannot be obtained by morphological imaging and can be used to assess the brain area responsible for consciousness.

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

kil K. E.; Biegon A.; Kil, K.-E.

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies inmore » the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 {+-} 2.21 Ci/{micro}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain aromatase, it may be useful in measuring letrozole distribution and pharmacokinetics in brain and peripheral organs.« less

Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study.

PubMed

Brody, Arthur L; Hubert, Robert; Enoki, Ryutaro; Garcia, Lizette Y; Mamoun, Michael S; Okita, Kyoji; London, Edythe D; Nurmi, Erika L; Seaman, Lauren C; Mandelkern, Mark A

2017-07-01

In the brain, microglia continuously scan the surrounding extracellular space in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of translocator protein (TSPO) 18 kDa, thereby making the TSPO expression a marker for neuroinflammation. We used the radiotracer [ 11 C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation. Forty-five participants (30 smokers and 15 non-smokers) completed the study and had usable data. Participants underwent a dynamic PET scanning session with bolus injection of [ 11 C]DAA1106 (with smokers in the satiated state) and blood draws during PET scanning to determine TSPO affinity genotype and plasma nicotine levels. Whole-brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (smoker vs non-smoker) and genotype as factors, thereby controlling for genotype. Smokers and non-smokers differed in whole-brain SUVs (P=0.006) owing to smokers having 16.8% lower values than non-smokers. The groups did not differ in injected radiotracer dose or body weight, which were used to calculate SUV. An inverse association was found between whole-brain SUV and reported cigarettes per day (P<0.05), but no significant relationship was found for plasma nicotine. Thus, smokers have less [ 11 C]DAA1106 binding globally than non-smokers, indicating less microglial activation. Study findings are consistent with much prior research demonstrating that smokers have impaired inflammatory functioning compared with non-smokers and that constituents of tobacco smoke other than nicotine affect inflammatory processes.

Influence of alcoholism and cholesterol on TSPO binding in brain: PET [11C]PBR28 studies in humans and rodents.

PubMed

Kim, Sung Won; Wiers, Corinde E; Tyler, Ryan; Shokri-Kojori, Ehsan; Jang, Yeon Joo; Zehra, Amna; Freeman, Clara; Ramirez, Veronica; Lindgren, Elsa; Miller, Gregg; Cabrera, Elizabeth A; Stodden, Tyler; Guo, Min; Demiral, Şükrü B; Diazgranados, Nancy; Park, Luke; Liow, Jeih-San; Pike, Victor; Morse, Cheryl; Vendruscolo, Leandro F; Innis, Robert B; Koob, George F; Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D

2018-05-03

Neuroinflammation appears to contribute to neurotoxicity observed with heavy alcohol consumption. To assess whether chronic alcohol results in neuroinflammation we used PET and [ 11 C]PBR28, a ligand that binds to the 18-kDa translocator protein (TSPO), to compare participants with an alcohol use disorder (AUD: n = 19) with healthy controls (HC: n = 17), and alcohol-dependent (n = 9) with -nondependent rats (n = 10). Because TSPO is implicated in cholesterol's transport for steroidogenesis, we investigated whether plasma cholesterol levels influenced [ 11 C]PBR28 binding. [ 11 C]PBR28 binding did not differ between AUD and HC. However, when separating by TSPO genotype rs6971, we showed that medium-affinity binders AUD participants showed lower [ 11 C]PBR28 binding than HC in regions of interest (whole brain, gray and white matter, hippocampus, and thalamus), but no group differences were observed in high-affinity binders. Cholesterol levels inversely correlated with brain [ 11 C]PBR28 binding in combined groups, due to a correlation in AUD participants. In rodents, we observed no differences in brain [ 11 C]PBR28 uptake between alcohol-dependent and -nondependent rats. These findings, which are consistent with two previous [ 11 C]PBR28 PET studies, may indicate lower activation of microglia in AUD, whereas failure to observe alcohol effects in the rodent model indicate that species differences do not explain the discrepancy with prior rodent autoradiographic studies reporting increases in TSPO binding with chronic alcohol. However, reduced binding in AUD participants could also reflect competition from endogenous TSPO ligands such as cholesterol; and since the rs6971 polymorphism affects the cholesterol-binding domain of TSPO this could explain why differences were observed only in medium-affinity binders.

A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome

PubMed Central

Steinhoff, Nikolaus; Heine, Astrid M.; Vogl, Julia; Weiss, Konrad; Aschraf, Asita; Hajek, Paul; Schnider, Peter; Tucek, Gerhard

2015-01-01

The global cerebral network allows music “ to do to us what it does.” While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people. Consequently, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing, and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT) provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS) during MT. Each patient had three PET investigations: (i) during a resting state, (ii) during the first exposure to MT, and (iii) during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week), while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34%) than in the control group after 5 weeks. The preliminary results suggest that MT activates the three brain regions described above. In this article, we present our approach to the neuroscience of MT and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research. PMID:26347603

A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome.

PubMed

Steinhoff, Nikolaus; Heine, Astrid M; Vogl, Julia; Weiss, Konrad; Aschraf, Asita; Hajek, Paul; Schnider, Peter; Tucek, Gerhard

2015-01-01

The global cerebral network allows music " to do to us what it does." While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people. Consequently, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing, and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT) provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS) during MT. Each patient had three PET investigations: (i) during a resting state, (ii) during the first exposure to MT, and (iii) during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week), while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34%) than in the control group after 5 weeks. The preliminary results suggest that MT activates the three brain regions described above. In this article, we present our approach to the neuroscience of MT and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research.

FDG-PET in early AD diagnosis.

PubMed

Chew, Jessica; Silverman, Daniel H S

2013-05-01

FDG-PET is a valuable tool that will continue to aid in identifying AD in its prodromal and early dementia stages, distinguishing it from other causes of dementia, and tracking progression of the disease. As brain FDG-PET scans and well-trained readers of these scans are becoming more widely available to clinicians who are becoming more informed about the role FDG-PET can play in early AD diagnosis, its use is expected to increase. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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.

[18F]FP-(+)-DTBZ PET study in a lactacystin-treated rat model of Parkinson disease.

PubMed

Weng, Chi-Chang; Huang, Siao-Lan; Chen, Zi-An; Lin, Kun-Ju; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Kung, Mei-Ping; Wey, Shiaw-Pyng; Hsu, Ching-Han

2017-08-01

Lactacystin has been used to establish rodent models of Parkinson disease (PD), with cerebral α-synuclein inclusions. This study evaluated the uptake of [ 18 F]9-fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]FP-(+)-DTBZ), a vesicular monoamine transporter type 2 (VMAT2)-targeting radiotracer, through positron emission tomography (PET) in lactacystin-treated rat brains. Adult male Sprague-Dawley rats were randomly treated with a single intracranial dose of lactacystin (2 or 5 μg) or saline (served as the sham control) into the left medial forebrain bundle. A 30-min static [ 18 F]FP-(+)-DTBZ brain PET scan was performed following an intravenous [ 18 F]FP-(+)-DTBZ dose (approximately 22 MBq) in each animal at 2 and 3 weeks after lactacystin treatment. Upon completing the last PET scans, the animals were killed, and their brains were dissected for ex vivo autoradiography (ARG) and immunohistochemical (IHC) staining of tyrosine hydroxylase (TH) as well as VMAT2. Both the 2- and 5-μg lactacystin-treated groups exhibited significantly decreased specific [ 18 F]FP-(+)-DTBZ uptake in the ipsilateral striata (I-ST) at 2 weeks (1.51 and 1.16, respectively) and 3 weeks (1.36 and 1.00, respectively) after lactacystin treatment, compared with the uptake in the corresponding contralateral striata (C-ST) (3.48 and 3.08 for the 2- and 5-μg lactacystin-treated groups, respectively, at 2 weeks; 3.36 and 3.11 for the 2- and 5-μg lactacystin-treated groups, respectively, at 3 weeks) and the sham controls (3.34-3.53). Lactacystin-induced decline in I-ST [ 18 F]FP-(+)-DTBZ uptake was also demonstrated through ex vivo ARG, and the corresponding dopaminergic neuron damage was confirmed by the results of TH- and VMAT2-IHC studies. In this PD model, lactacystin-induced dopaminergic terminal damage in the ipsilateral striatum could be clearly visualized through in vivo [ 18 F]FP-(+)-DTBZ PET imaging. This may serve as a useful approach for evaluating the effectiveness of new treatments for PD.

[18F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model.

PubMed

Vignal, Nicolas; Cisternino, Salvatore; Rizzo-Padoin, Nathalie; San, Carine; Hontonnou, Fortune; Gelé, Thibaut; Declèves, Xavier; Sarda-Mantel, Laure; Hosten, Benoît

2018-06-07

[ 18 F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [ 18 F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation induced by an intraperitoneal injection of Salmonella enterica serovar Typhimurium lipopolysaccharides (LPS; 5 mg/kg) 24 h before PET imaging. [ 18 F]FEPPA was synthesized by nucleophilic substitution (90 °C, 10 min) with tosylated precursor, followed by improved semi-preparative HPLC purification (retention time 14 min). [ 18 F]FEPPA radiosynthesis were carried out in 55 min (from EOB). The non-decay corrected radiochemical yield were 34 ± 2% ( n = 17), and the radiochemical purity greater than 99%, with a molar activity of 198 ± 125 GBq/µmol at the end of synthesis. Western blot analysis demonstrated a 2.2-fold increase in TSPO brain expression in the LPS treated mice compared to controls. This was consistent with the significant increase of [ 18 F]FEPPA brain total volume of distribution ( V T ) estimated with pharmacokinetic modelling. In conclusion, [ 18 F]FEPPA radiosynthesis was implemented with high yields. The new purification/formulation with only class 3 solvents is more suitable for in vivo studies.

Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein.

PubMed

Seneca, Nicholas; Zoghbi, Sami S; Liow, Jeih-San; Kreisl, William; Herscovitch, Peter; Jenko, Kimberly; Gladding, Robert L; Taku, Andrew; Pike, Victor W; Innis, Robert B

2009-05-01

P-glycoprotein (P-gp) is a membrane-bound efflux pump that limits the distribution of drugs to several organs of the body. At the blood-brain barrier, P-gp blocks the entry of both loperamide and its metabolite, N-desmethyl-loperamide (N-dLop), and thereby prevents central opiate effects. Animal studies have shown that (11)C-dLop, compared with (11)C-loperamide, is an especially promising radiotracer because it generates negligible radiometabolites that enter the brain. The purposes of this study were to determine whether (11)C-dLop is a substrate for P-gp at the blood-brain barrier in humans and to measure the distribution of radioactivity in the entire body to estimate radiation exposure. Brain PET scans were acquired in 4 healthy subjects for 90 min and included concurrent measurements of the plasma concentration of unchanged radiotracer. Time-activity data from the whole brain were quantified using a 1-tissue-compartment model to estimate the rate of entry (K(1)) of radiotracer into the brain. Whole-body PET scans were acquired in 8 healthy subjects for 120 min. For brain imaging, after the injection of (11)C-dLop the concentration of radioactivity in the brain was low (standardized uptake value, approximately 15%) and stable after approximately 20 min. In contrast, uptake of radioactivity in the pituitary was about 50-fold higher than that in the brain. The plasma concentration of (11)C-dLop declined rapidly, but the percentage composition of plasma was unusually stable, with the parent radiotracer constituting 85% of total radioactivity after approximately 5 min. The rate of brain entry was low (K(1) = 0.009 +/- 0.002 mL.cm(-3).min(-1); n = 4). For whole-body imaging, as a measure of radiation exposure to the entire body the effective dose of (11)C-dLop was 7.8 +/- 0.6 muSv/MBq (n = 8). The low brain uptake of radioactivity is consistent with (11)C-dLop being a substrate for P-gp in humans and confirms that this radiotracer generates negligible quantities of brain-penetrant radiometabolites. In addition, the low rate of K(1) is consistent with P-gp rapidly effluxing substrates while they transit through the lipid bilayer. The radiation exposure of (11)C-dLop is similar to that of many other (11)C-radiotracers. Thus, (11)C-dLop is a promising radiotracer to study the function of P-gp at the blood-brain barrier, at which impaired function would allow increased uptake into the brain.

Positron emission tomography assessment of 8-OH-DPAT-mediated changes in an index of cerebral glucose metabolism in female marmosets

PubMed Central

Converse, Alexander K.; Aubert, Yves; Farhoud, Mohammed; Weichert, Jamey P.; Rowland, Ian J.; Ingrisano, Nicole M.; Allers, Kelly A.; Sommer, Bernd; Abbott, David H.

2013-01-01

As part of a larger experiment investigating serotonergic regulation of female marmoset sexual behavior, this study was designed to (1) advance methods for PET imaging of common marmoset monkey brain, (2) measure normalized FDG uptake as an index of local cerebral metabolic rates for glucose, and (3) study changes induced in this index of cerebral glucose metabolism by chronic treatment of female marmosets with a serotonin 1A receptor (5-HT1A) agonist. We hypothesized that chronic treatment with the 5-HT1A agonist 8-OH-DPAT would alter the glucose metabolism index in dorsal raphe (DR), medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus (VMH), and field CA1 of hippocampus. Eight adult ovariectomized female common marmosets (Callithrix jacchus) were studied with and without estradiol replacement. In a crossover design, each subject was treated daily with 8-OH-DPAT (0.1 mg/kg SC daily) or saline. After 42–49 days of treatment, the glucose metabolism radiotracer FDG was administered to each female immediately prior to 30 min of interaction with her male pairmate, after which the subject was anesthetized and imaged by PET. Whole brain normalized PET images were analyzed with anatomically defined regions of interest (ROI). Whole brain voxelwise mapping was also used to explore treatment effects and correlations between alterations in the glucose metabolism index and pairmate interactions. The rank order of normalized FDG uptake was VMH/mPOA>DR>mPFC/CA1 in both conditions. 8-OH-DPAT did not induce alterations in the glucose metabolism index in ROIs. Voxelwise mapping showed a significant reduction in normalized FDG uptake in response to 8-OH-DPAT in a cluster in medial occipital cortex as well as a significant correlation between increased rejection of mount attempts and reduced normalized FDG uptake in an overlapping cluster. In conclusion, PET imaging has been used to measure FDG uptake relative to whole brain in marmoset monkeys. Voxelwise mapping shows that 8-OH-DPAT reduces this index of glucose metabolism in medial occipital cortex, consistent with alterations in female sexual behavior. PMID:22233732

Clinical utility of FDG-PET in amyotrophic lateral sclerosis and Huntington's disease.

PubMed

Agosta, Federica; Altomare, Daniele; Festari, Cristina; Orini, Stefania; Gandolfo, Federica; Boccardi, Marina; Arbizu, Javier; Bouwman, Femke; Drzezga, Alexander; Nestor, Peter; Nobili, Flavio; Walker, Zuzana; Pagani, Marco

2018-05-01

To evaluate the incremental value of FDG-PET over clinical tests in: (i) diagnosis of amyotrophic lateral sclerosis (ALS); (ii) picking early signs of neurodegeneration in patients with a genetic risk of Huntington's disease (HD); and detecting metabolic changes related to cognitive impairment in (iii) ALS and (iv) HD patients. Four comprehensive literature searches were conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on these four diagnostic scenarios. The availability of evidence was good for FDG-PET utility to support the diagnosis of ALS, poor for identifying presymptomatic subjects carrying HD mutation who will convert to HD, and lacking for identifying cognitive-related metabolic changes in both ALS and HD. After the Delphi consensual procedure, the panel did not support the clinical use of FDG-PET for any of the four scenarios. Relative to other neurodegenerative diseases, the clinical use of FDG-PET in ALS and HD is still in its infancy. Once validated by disease-control studies, FDG-PET might represent a potentially useful biomarker for ALS diagnosis. FDG-PET is presently not justified as a routine investigation to predict conversion to HD, nor to detect evidence of brain dysfunction justifying cognitive decline in ALS and HD.

The role of amino acid PET in the light of the new WHO classification 2016 for brain tumors.

PubMed

Suchorska, Bogdana; Albert, Nathalie L; Bauer, Elena K; Tonn, Jörg-Christian; Galldiks, Norbert

2018-04-26

Since its introduction in 2016, the revision of the World Health Organization (WHO) classification of central nervous system tumours has already changed the diagnostic and therapeutic approach in glial tumors. Blurring the lines between entities formerly labelled as "high-grade" or "low-grade", molecular markers define distinct biological subtypes with different clinical course. This new classification raises the demand for non-invasive imaging methods focussing on depicting metabolic processes. We performed a review of current literature on the use of amino acid PET (AA-PET) for obtaining diagnostic or prognostic information on glioma in the setting of the current WHO 2016 classification. So far, only a few studies have focussed on combining molecular genetic information and metabolic imaging using AA-PET. The current review summarizes the information available on "molecular grading" as well as prognostic information obtained from AA-PET and delivers an insight into a possible interrelation between metabolic imaging and glioma genetics. Within the framework of molecular characterization of gliomas, metabolic imaging using AA-PET is a promising tool for non-invasive characterisation of molecular features and to provide additional prognostic information. Further studies incorporating molecular and metabolic features are necessary to improve the explanatory power of AA-PET in glial tumors.

Reduction-responsive PEtOz-SS-PCL micelle with tailored size to overcome blood-brain barrier and enhance doxorubicin antiglioma effect.

PubMed

Li, Yuling; Baiyang, Li; Leran, Bu; Zhen, Wang; Yandong, Xie; Baixiang, Du; Dandan, Zhu; Yufu, Zhu; Jun, Liang; Rutong, Yu; Hongmei, Liu

2017-11-01

A series of novel reduction-responsive micelles with tailored size were designed and prepared to release doxorubicin (DOX) for treating glioma, which were developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly (ε-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small size and rapid drug release in reductive intracellular environments. Biodistribution and in vivo imaging studies in C6 glioma mice tumor model showed that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior accumulation and fast drug release in tumor sites. In vivo antitumor activity demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6-Luci cells-bearing mice. This study shows great potential in tailoring the micelle size and introducing the responsive bonds or compartment for intracellular drug delivery and release in glioma treatment by designing the architecture of the polymer.

Chalcone Based Homodimeric PET Agent, 11C-(Chal)2DEA-Me, for Beta Amyloid Imaging: Synthesis and Bioevaluation.

PubMed

Chauhan, Kanchan; Tiwari, Anjani K; Chadha, Nidhi; Kaul, Ankur; Singh, Ajai Kumar; Datta, Anupama

2018-04-02

Homodimeric chalcone based 11 C-PET radiotracer, 11 C-(Chal) 2 DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aβ) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aβ fibrils. The bivalent ligand 11 C-(Chal) 2 DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11 C-Chal-Me, and classical Aβ agents. The radiolabeling yield with carbon-11 was 40-55% (decay corrected) with specific activity of 65-90 GBq/μmol. A significant ( p < 0.0001) improvement in the binding affinity of 11 C-(Chal) 2 DEA-Me with synthetic Aβ42 aggregates over the monomer, 11 C-Chal-Me, demonstrates the utility of the bivalent approach. The PET imaging and biodistribution data displayed suitable brain pharmacokinetics of both ligands with higher brain uptake in the case of the bivalent ligand. Metabolite analysis of healthy ddY mouse brain homogenates exhibited high stability of the radiotracers in the brain with >93% intact tracer at 30 min post injection. Both chalcone derivatives were fluorescent in nature and demonstrated significant changes in the emission properties after binding with Aβ42. The preliminary analysis indicates high potential of 11 C-(Chal) 2 DEA-Me as in vivo Aβ42 imaging tracer and highlights the significance of the bivalent approach to achieve a higher biological response for detection of early stages of amyloidosis.

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.

Anticholinesterase Effect on Motor Kinematic Measures and Brain Activation in Parkinson’s Disease

PubMed Central

Mentis, Marc J.; Delalot, Dominique; Naqvi, Hassan; Gordon, Mark F.; Gudesblatt, Mark; Edwards, Christine; Donatelli, Luke; Dhawan, Vijay; Eidelberg, David

2015-01-01

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson’s disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity. PMID:16228997

Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging.

PubMed

Bernier, Michaël; Croteau, Etienne; Castellano, Christian-Alexandre; Cunnane, Stephen C; Whittingstall, Kevin

2017-04-15

Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas. Copyright © 2017 Elsevier Inc. All rights reserved.

Semi-Supervised Tripled Dictionary Learning for Standard-dose PET Image Prediction using Low-dose PET and Multimodal MRI

PubMed Central

Wang, Yan; Ma, Guangkai; An, Le; Shi, Feng; Zhang, Pei; Lalush, David S.; Wu, Xi; Pu, Yifei; Zhou, Jiliu; Shen, Dinggang

2017-01-01

Objective To obtain high-quality positron emission tomography (PET) image with low-dose tracer injection, this study attempts to predict the standard-dose PET (S-PET) image from both its low-dose PET (L-PET) counterpart and corresponding magnetic resonance imaging (MRI). Methods It was achieved by patch-based sparse representation (SR), using the training samples with a complete set of MRI, L-PET and S-PET modalities for dictionary construction. However, the number of training samples with complete modalities is often limited. In practice, many samples generally have incomplete modalities (i.e., with one or two missing modalities) that thus cannot be used in the prediction process. In light of this, we develop a semi-supervised tripled dictionary learning (SSTDL) method for S-PET image prediction, which can utilize not only the samples with complete modalities (called complete samples) but also the samples with incomplete modalities (called incomplete samples), to take advantage of the large number of available training samples and thus further improve the prediction performance. Results Validation was done on a real human brain dataset consisting of 18 subjects, and the results show that our method is superior to the SR and other baseline methods. Conclusion This work proposed a new S-PET prediction method, which can significantly improve the PET image quality with low-dose injection. Significance The proposed method is favorable in clinical application since it can decrease the potential radiation risk for patients. PMID:27187939

Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in 64Cu PET Imaging for Alzheimer's Disease.

PubMed

Sharma, Anuj K; Schultz, Jason W; Prior, John T; Rath, Nigam P; Mirica, Liviu M

2017-11-20

Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, 11 C and 18 F, have short half-lives, and their usage is thus somewhat limited. By comparison, the 64 Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu 2+ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid β fibrillar aggregates. Determination of the protonation constants (pK a values) and stability constants (log β values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel 64 Cu PET imaging agents for Alzheimer's disease.

Real-time 3D motion tracking for small animal brain PET

NASA Astrophysics Data System (ADS)

Kyme, A. Z.; Zhou, V. W.; Meikle, S. R.; Fulton, R. R.

2008-05-01

High-resolution positron emission tomography (PET) imaging of conscious, unrestrained laboratory animals presents many challenges. Some form of motion correction will normally be necessary to avoid motion artefacts in the reconstruction. The aim of the current work was to develop and evaluate a motion tracking system potentially suitable for use in small animal PET. This system is based on the commercially available stereo-optical MicronTracker S60 which we have integrated with a Siemens Focus-220 microPET scanner. We present measured performance limits of the tracker and the technical details of our implementation, including calibration and synchronization of the system. A phantom study demonstrating motion tracking and correction was also performed. The system can be calibrated with sub-millimetre accuracy, and small lightweight markers can be constructed to provide accurate 3D motion data. A marked reduction in motion artefacts was demonstrated in the phantom study. The techniques and results described here represent a step towards a practical method for rigid-body motion correction in small animal PET. There is scope to achieve further improvements in the accuracy of synchronization and pose measurements in future work.

PET imaging in the assessment of normal and impaired cognitive function.

PubMed

Silverman, Daniel H S; Alavi, Abass

2005-01-01

PET has been used to directly quantify several processes relevant to the status of cerebral health and function, including cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism, and cerebral glucose use. Clinically, the most commonly performed PET studies of the brain are performed with fluorine-18-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic use in evaluating patients who have cognitive impairment, and in distinguishing among primary neurodegenerative dementias and other causes of cognitive decline. In certain pathologic circumstances, the normal coupling between blood flow and metabolic needs may be disturbed, and changes in oxygen extraction fraction can have significant prognostic value.

Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.

PubMed

Li, Yuxin; Tafti, Bashir A; Shaba, Wisam; Berenji, Gholam R

2011-07-01

A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study.

Correction of partial volume effect in (18)F-FDG PET brain studies using coregistered MR volumes: voxel based analysis of tracer uptake in the white matter.

PubMed

Coello, Christopher; Willoch, Frode; Selnes, Per; Gjerstad, Leif; Fladby, Tormod; Skretting, Arne

2013-05-15

A voxel-based algorithm to correct for partial volume effect in PET brain volumes is presented. This method (named LoReAn) is based on MRI based segmentation of anatomical regions and accurate measurements of the effective point spread function of the PET imaging process. The objective is to correct for the spill-out of activity from high-uptake anatomical structures (e.g. grey matter) into low-uptake anatomical structures (e.g. white matter) in order to quantify physiological uptake in the white matter. The new algorithm is presented and validated against the state of the art region-based geometric transfer matrix (GTM) method with synthetic and clinical data. Using synthetic data, both bias and coefficient of variation were improved in the white matter region using LoReAn compared to GTM. An increased number of anatomical regions doesn't affect the bias (<5%) and misregistration affects equally LoReAn and GTM algorithms. The LoReAn algorithm appears to be a simple and promising voxel-based algorithm for studying metabolism in white matter regions. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1992--December 31, 1992

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

Cooper, M.; Beck, R.N.

1992-06-01

This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib

NASA Astrophysics Data System (ADS)

Collier, Thomas Lee; Normandin, Marc D.; Stephenson, Nickeisha A.; Livni, Eli; Liang, Steven H.; Wooten, Dustin W.; Esfahani, Shadi A.; Stabin, Michael G.; Mahmood, Umar; Chen, Jianqing; Wang, Wei; Maresca, Kevin; Waterhouse, Rikki N.; El Fakhri, Georges; Richardson, Paul; Vasdev, Neil

2017-06-01

Lorlatinib (PF-06463922) is a next-generation small-molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for non-small cell lung cancers. An early goal is to measure the concentrations of this drug in brain tumour lesions of lung cancer patients, as penetration of the blood-brain barrier is important for optimal therapeutic outcomes. Here we prepare both 11C- and 18F-isotopologues of lorlatinib to determine the biodistribution and whole-body dosimetry assessments by positron emission tomography (PET). Non-traditional radiolabelling strategies are employed to enable an automated multistep 11C-labelling process and an iodonium ylide-based radiofluorination. Carbon-11-labelled lorlatinib is routinely prepared with good radiochemical yields and shows reasonable tumour uptake in rodents. PET imaging in non-human primates confirms that this radiotracer has high brain permeability.

Effect of gender on glucose utilization rates in healthy humans: A positron emission tomography study

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

Miura, S.A.; Schapiro, M.B.; Grady, C.L.

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate thatmore » there are no differences in resting regional cerebral glucose utilization between young men and women.« less

Mood state and cerebral metabolism in persons with age-associated memory impairment.

PubMed

Cherrier, M M; Small, G W; Komo, S; La Rue, A

1997-12-30

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4 +/- 9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.

[Features of Acquired Immunodeficiency Syndrome-related Lymphoma on (18)F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography].

PubMed

Niu, Na; Zhu, Zhao-hui; Ma, Yan-ru; Xing, Hai-qun; Li, Fang

2015-10-01

To analyze the imaging features of (18)F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography(PET)/computed tomography (CT) in acquired immune deficiency syndrome-related lymphoma (ARL) patients correlated with their clinical signs, symptoms, and treatments. Five ARL patients underwent ¹⁸F-FDG PET/CT at Peking Union Medical College Hospital from October 2008 to January 2013. Two patients received two additional follow-up studies 6 months later. Among these 5 patients, ¹⁸FDG-PET/CT helped in diagnosis of two patient and changed therapeutic strategy in other two patients. In two patients underwent ¹⁸F-FDG PET/CT brain scans, low-metabolism lesion was newly found in cerebral cortex. Of 4 patients receiving highly active antiretroviral therapy, PET/CT also demonstrated diffusely elevated ¹⁸F-FDG uptake in subcutaneous adipose tissue in two patients. ¹⁸F-FDG PET/CT is a highly useful tool in the diagnosis and treatment of ARL patients, in particular in the identification of associated encephalopathy and lipodystrophy.

Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm.

PubMed

Seo, Jeho; Cho, Hojin; Kim, Gun Tae; Kim, Chul Hoon; Kim, Dong Goo

2017-10-01

Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress. Copyright © 2016 Elsevier Inc. All rights reserved.

P-glycoprotein (ABCB1) inhibits the influx and increases the efflux of 11C-metoclopramide across the blood-brain barrier: a PET study on non-human primates.

PubMed

Auvity, Sylvain; Caillé, Fabien; Marie, Solène; Wimberley, Catriona; Bauer, Martin; Langer, Oliver; Buvat, Irène; Goutal, Sébastien; Tournier, Nicolas

2018-05-10

Rationale : PET imaging using radiolabeled high-affinity substrates of P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of 11 C-metoclopramide, as a model weak ABCB1 substrate, in non-human primates. Methods : The regional brain kinetics of a tracer dose of 11 C-metoclopramide (298 ± 44 MBq) were assessed in baboons using PET without (n = 4) or with intravenous co-infusion of the ABCB1 inhibitor tariquidar (4 mg/kg/h, n = 4). Metabolite-corrected arterial input functions were generated to estimate the regional volume of distribution ( V T ) as well as the influx ( K 1 ) and efflux ( k 2 ) rate constants, using a one-tissue compartment model. Modeling outcome parameters were correlated with image-derived parameters, i.e. area under the curve AUC 0-30 min and AUC 30-60 min (SUV.min) as well as the elimination slope (k E ; min -1 ) from 30 to 60 min of the regional time-activity curves. Results : Tariquidar significantly increased the brain distribution of 11 C-metoclopramide ( V T = 4.3 ± 0.5 mL/cm 3 and 8.7 ± 0.5 mL/cm 3 for baseline and ABCB1 inhibition conditions, respectively, P<0.001), with a 1.28-fold increase in K 1 (P < 0.05) and a 1.64-fold decrease in k 2 (P < 0.001). The effect of tariquidar was homogeneous across different brain regions. The most sensitive parameters to ABCB1 inhibition were V T (2.02-fold increase) and AUC 30-60 min (2.02-fold increase). V T was significantly (P < 0.0001) correlated with AUC 30-60 min (r 2 = 0.95), AUC 0-30 min (r 2 = 0.87) and k E (r 2 = 0.62). Conclusion : 11 C-metoclopramide PET imaging revealed the relative importance of both the influx hindrance and efflux enhancement components of ABCB1 in a relevant model of the human BBB. The overall impact of ABCB1 on drug delivery to the brain can be non-invasively estimated from image-derived outcome parameters without the need for an arterial input function. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Synthesis and preliminary biological evaluation of S-11C-methyl-D-cysteine as a new amino acid PET tracer for cancer imaging.

PubMed

Huang, Tingting; Tang, Ganghua; Wang, Hongliang; Nie, Dahong; Tang, Xiaolan; Liang, Xiang; Hu, Kongzhen; Yi, Chang; Yao, Baoguo; Tang, Caihua

2015-04-01

S-(11)C-methyl-L-cysteine (LMCYS) is an attractive amino acid tracer for clinical tumor positron emission tomography (PET) imaging. D-isomers of some radiolabeled amino acids are potential PET tracers for tumor imaging. In this work, S-(11)C-methyl-D-cysteine (DMCYS), a D-amino acid isomer of S-(11)C-methyl-cysteine for tumor imaging was developed and evaluated. DMCYS was prepared by (11)C-methylation of the precursor D-cysteine, with an uncorrected radiochemical yield over 50 % from (11)CH3I within a total synthesis time from (11)CO2 about 12 min. In vitro competitive inhibition studies showed that DMCYS uptake was primarily transported through the Na(+)-independent system L, and also the Na(+)-dependent system B(0,+) and system ASC, with almost no system A. In vitro incorporation experiments indicated that almost no protein incorporation was found in Hepa 1-6 hepatoma cell lines. Biodistribution studies demonstrated higher uptake of DMCYS in pancreas and liver at 5 min post-injection, relatively lower uptake in brain and muscle, and faster radioactivity clearance from most tissues than those of L-isomer during the entire observation time. In the PET imaging of S180 fibrosarcoma-bearing mice and turpentine-induced inflammatory model mice, 2-(18)F-fluoro-2-deoxy-D-glucose (FDG) exhibited significantly high accumulation in both tumor and inflammatory lesion with low tumor-to-inflammation ratio of 1.40, and LMCYS showed low tumor-to-inflammation ratio of 1.64 at 60 min post-injection. By contrast, DMCYS showed moderate accumulation in tumor and very low uptake in inflammatory lesion, leading to relatively higher tumor-to-inflammation ratio of 2.25 than (11)C-methyl-L-methionine (MET) (1.85) at 60 min post-injection. Also, PET images of orthotopic transplanted glioma models demonstrated that low uptake of DMCYS in normal brain tissue and high uptake in brain glioma tissue were observed. The results suggest that DMCYS is a little better than the corresponding L-isomers as a potential PET tumor-detecting agent and is superior to MET and FDG in the differentiation of tumor from inflammation.

Quantitative Evaluation of 2 Scatter-Correction Techniques for 18F-FDG Brain PET/MRI in Regard to MR-Based Attenuation Correction.

PubMed

Teuho, Jarmo; Saunavaara, Virva; Tolvanen, Tuula; Tuokkola, Terhi; Karlsson, Antti; Tuisku, Jouni; Teräs, Mika

2017-10-01

In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. Methods: The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. Results: MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. Conclusion: The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight 18 F-FDG PET/MR brain imaging. The SSS algorithm was not affected significantly by MRAC. The performance of the MC-SSS algorithm is comparable but not superior to TF-SSS, warranting further investigations of algorithm optimization and performance with different radiotracers and time-of-flight imaging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

SU-E-J-104: Single Photon Image From PET with Insertable SPECT Collimator for Boron Neutron Capture Therapy: A Feasibility Study

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

Jung, J; Yoon, D; Suh, T

2014-06-01

Purpose: The aim of our proposed system is to confirm the feasibility of extraction of two types of images from one positron emission tomography (PET) module with an insertable collimator for brain tumor treatment during the BNCT. Methods: Data from the PET module, neutron source, and collimator was entered in the Monte Carlo n-particle extended (MCNPX) source code. The coincidence events were first compiled on the PET detector, and then, the events of the prompt gamma ray were collected after neutron emission by using a single photon emission computed tomography (SPECT) collimator on the PET. The obtaining of full widthmore » at half maximum (FWHM) values from the energy spectrum was performed to collect effective events for reconstructed image. In order to evaluate the images easily, five boron regions in a brain phantom were used. The image profiles were extracted from the region of interest (ROI) of a phantom. The image was reconstructed using the ordered subsets expectation maximization (OSEM) reconstruction algorithm. The image profiles and the receiver operating characteristic (ROC) curve were compiled for quantitative analysis from the two kinds of reconstructed image. Results: The prompt gamma ray energy peak of 478 keV appeared in the energy spectrum with a FWHM of 41 keV (6.4%). On the basis of the ROC curve in Region A to Region E, the differences in the area under the curve (AUC) of the PET and SPECT images were found to be 10.2%, 11.7%, 8.2% (center, Region C), 12.6%, and 10.5%, respectively. Conclusion: We attempted to acquire the PET and SPECT images simultaneously using only PET without an additional isotope. Single photon images were acquired using an insertable collimator on a PET detector. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning (MSIP)(Grant No.2009 00420) and the Radiation Technology R and D program (Grant No.2013M2A2A7043498), Republic of Korea.« less

Memory deficits due to brain injury: unique PET findings and dream alterations

PubMed Central

Nishida, Masaki; Nariai, Tadashi; Hiura, Mikio; Ishii, Kenji; Nishikawa, Toru

2011-01-01

The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and 11C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the relief of the sleep-related symptoms. FDG-PET showed considerable improvement in glucose metabolism when he had recovered, however, evidence of neural loss remained in the FMZ-PET findings. PMID:22674950

Trans-synaptic (GABA-dopamine) modulation of cocaine induced dopamine release: A potential therapeutic strategy for cocaine abuse

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

Dewey, S.L.; Straughter-Moore, R.; Chen, R.

We recently developed a new experimental strategy for measuring interactions between functionally-linked neurotransmitter systems in the primate and human brain with PET. As part of this research, we demonstrated that increases in endogenous GABA concentrations significantly reduced striatal dopamine concentrations in the primate brain. We report here the application of the neurotransmitter interaction paradigm with PET and with microdialysis to the investigation of a novel therapeutic strategy for treating cocaine abuse based on the ability of GABA to inhibit cocaine induced increases in striatal dopamine. Using gamma-vinyl GABA (GVG, a suicide inhibitor of GABA transaminase), we performed a series ofmore » PET studies where animals received a baseline PET scan with labeled raclopride injection, animals received cocaine (2.0 mg/kg). Normally, a cocaine challenge significantly reduces the striatal binding of {sup 11}C-raclopride. However, in animals pretreated with GVG, {sup 11}C-raclopride binding was less affected by a cocaine challenge compared to control studies. Furthermore, microdialysis studies in freely moving rats demonstrate that GVG (300 mg/kg) significantly inhibited cocaine-induced increases in extracellular dopamine release. GVG also attenuated cocaine-induced increases in locomotor activity. However, at a dose of 100 mg/kg, GVG had no effect. Similar findings were obtained with alcohol. Alcohol pretreatment dose dependantly (1-4 g/kg) inhibited cocaine-induced increases in extracellular dopamine concentrations in freely moving rats. Taken together, these studies suggest that therapeutic strategies targeted at increasing central GABA concentrations may be beneficial for the treatment of cocaine abuse.« less

The use of positron emission tomography in pion radiotherapy.

PubMed

Goodman, G B; Lam, G K; Harrison, R W; Bergstrom, M; Martin, W R; Pate, B D

1986-10-01

The radioactive debris produced by pion radiotherapy can be imaged by the technique of Positron Emission Tomography (PET) as a method of non-invasive in situ verification of the pion treatment. This paper presents the first visualization of the pion stopping distribution within a tumor in a human brain using PET. Together with the tissue functional information provided by the standard PET scans using radiopharmaceuticals, the combination of pion with PET technique can provide a much better form of radiotherapy than the use of conventional radiation in both treatment planning and verification.

Kinetic modeling and long-term test-retest reproducibility of the mGluR5 PET tracer 18F-FPEB in human brain.

PubMed

Leurquin-Sterk, Gil; Postnov, Andrey; de Laat, Bart; Casteels, Cindy; Celen, Sofie; Crunelle, Cleo L; Bormans, Guy; Koole, Michel; Van Laere, Koen

2016-04-01

(18)F-FPEB is a promising PET tracer for studying the metabotropic glutamate subtype 5 receptor (mGluR5) expression in neuropsychiatric disorders. To assess the potential of (18)F-FPEB for longitudinal mGluR5 evaluation in patient studies, we evaluated the long-term test-retest reproducibility using various kinetic models in the human brain. Nine healthy volunteers underwent consecutive scans separated by a 6-month period. Dynamic PET was combined with arterial sampling and radiometabolite analysis. Total distribution volume (V(T)) and nondisplaceable binding potential (BP(ND)) were derived from a two-tissue compartment model without constraints (2TCM) and with constraining the K(1)/k(2) ratio to the value of either cerebellum (2TCM-CBL) or pons (2TCM-PONS). The effect of fitting different functions to the tracer parent fractions and reducing scan duration were assessed. Regional absolute test-retest variability (aTRV), coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were computed. The 2TCM-CBL showed best fits. The mean 6-month aTRV of V(T) ranged from 8 to 13% (CR < 25%) with ICC > 0.6 for all kinetic models. BPND from 2TCM-CBL with a sigmoid fit for the parent fractions showed the best reproducibility, with aTRV ≤ 7% (CR < 16%) and ICC > 0.9 in most regions. Reducing the scan duration from 90 to 60 min did not affect reproducibility. These results demonstrate for the first time that (18)F-FPEB brain PET has good long-term reproducibility, therefore validating its use to monitor mGluR5 expression in longitudinal clinical studies. We suggest a 2TCM-CBL with fitting a sigmoid function to the parent fractions to be optimal for this tracer. © 2016 Wiley Periodicals, Inc.

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.

Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations.

PubMed

Tronel, Claire; Largeau, Bérenger; Santiago Ribeiro, Maria Joao; Guilloteau, Denis; Dupont, Anne-Claire; Arlicot, Nicolas

2017-04-11

Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians' expectations.

NEMA NU 4-2008 validation and applications of the PET-SORTEO Monte Carlo simulations platform for the geometry of the Inveon PET preclinical scanner

NASA Astrophysics Data System (ADS)

Boisson, F.; Wimberley, C. J.; Lehnert, W.; Zahra, D.; Pham, T.; Perkins, G.; Hamze, H.; Gregoire, M.-C.; Reilhac, A.

2013-10-01

Monte Carlo-based simulation of positron emission tomography (PET) data plays a key role in the design and optimization of data correction and processing methods. Our first aim was to adapt and configure the PET-SORTEO Monte Carlo simulation program for the geometry of the widely distributed Inveon PET preclinical scanner manufactured by Siemens Preclinical Solutions. The validation was carried out against actual measurements performed on the Inveon PET scanner at the Australian Nuclear Science and Technology Organisation in Australia and at the Brain & Mind Research Institute and by strictly following the NEMA NU 4-2008 standard. The comparison of simulated and experimental performance measurements included spatial resolution, sensitivity, scatter fraction and count rates, image quality and Derenzo phantom studies. Results showed that PET-SORTEO reliably reproduces the performances of this Inveon preclinical system. In addition, imaging studies showed that the PET-SORTEO simulation program provides raw data for the Inveon scanner that can be fully corrected and reconstructed using the same programs as for the actual data. All correction techniques (attenuation, scatter, randoms, dead-time, and normalization) can be applied on the simulated data leading to fully quantitative reconstructed images. In the second part of the study, we demonstrated its ability to generate fast and realistic biological studies. PET-SORTEO is a workable and reliable tool that can be used, in a classical way, to validate and/or optimize a single PET data processing step such as a reconstruction method. However, we demonstrated that by combining a realistic simulated biological study ([11C]Raclopride here) involving different condition groups, simulation allows one also to assess and optimize the data correction, reconstruction and data processing line flow as a whole, specifically for each biological study, which is our ultimate intent.

First Human Brain Imaging by the jPET-D4 Prototype With a Pre-Computed System Matrix

NASA Astrophysics Data System (ADS)

Yamaya, Taiga; Yoshida, Eiji; Obi, Takashi; Ito, Hiroshi; Yoshikawa, Kyosan; Murayama, Hideo

2008-10-01

The jPET-D4 is a novel brain PET scanner which aims to achieve not only high spatial resolution but also high scanner sensitivity by using 4-layer depth-of-interaction (DOI) information. The dimensions of a system matrix for the jPET-D4 are 3.3 billion (lines-of-response) times 5 million (image elements) when a standard field-of-view (FOV) of 25 cm diameter is sampled with a (1.5 mm)3 voxel . The size of the system matrix is estimated as 117 petabytes (PB) with the accuracy of 8 bytes per element. An on-the-fly calculation is usually used to deal with such a huge system matrix. However we cannot avoid extension of the calculation time when we improve the accuracy of system modeling. In this work, we implemented an alternative approach based on pre-calculation of the system matrix. A histogram-based 3D OS-EM algorithm was implemented on a desktop workstation with 32 GB memory installed. The 117 PB system matrix was compressed under the limited amount of computer memory by (1) eliminating zero elements, (2) applying the DOI compression (DOIC) method and (3) applying rotational symmetry and an axial shift property of the crystal arrangement. Spanning, which degrades axial resolution, was not applied. The system modeling and the DOIC method, which had been validated in 2D image reconstruction, were expanded into 3D implementation. In particular, a new system model including the DOIC transformation was introduced to suppress resolution loss caused by the DOIC method. Experimental results showed that the jPET-D4 has almost uniform spatial resolution of better than 3 mm over the FOV. Finally the first human brain images were obtained with the jPET-D4.

A microPET comparison of the effects of etifoxine and diazepam on [(11)C]flumazenil uptake in rat brains.

PubMed

Bouillot, Caroline; Bonnefoi, Frédéric; Liger, François; Zimmer, Luc

2016-01-26

Using positron emission tomography (PET), the present study assessed the binding of [(11)C]flumazenil to GABA-A receptors in anesthetized rats following a single intravenous injection of an active dose of either etifoxine (25mg/kg) or diazepam (1mg/kg), which are both anxiolytic drugs. [(11)C]flumazenil binding was measured in five discrete brain structures, namely the caudate putamen, hippocampus, cerebellum, occipital cortex and parietal cortex. As expected, diazepam injection produced a significant decrease in [(11)C]flumazenil binding, which was interpreted as benzodiazepine GABA-A receptor occupancy, whereas etifoxine increased the binding of [(11)C]flumazenil. This first use of in vivo imaging after etifoxine administration revealed the activated binding pattern of [(11)C]flumazenil and highlighted the pharmacological differences between etifoxine and benzodiazepines. Using the same [(11)C]flumazenil radiotracer, PET neuroimaging could be applied to larger animals and, ultimately, to human subjects, thus providing new perspectives for better defining the molecular pharmacology of etifoxine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PET Imaging in Huntington's Disease.

PubMed

Roussakis, Andreas-Antonios; Piccini, Paola

2015-01-01

To date, little is known about how neurodegeneration and neuroinflammation propagate in Huntington's disease (HD). Unfortunately, no treatment is available to cure or reverse the progressive decline of function caused by the disease, thus considering HD a fatal disease. Mutation gene carriers typically remain asymptomatic for many years although alterations in the basal ganglia and cortex occur early on in mutant HD gene-carriers. Positron Emission Tomography (PET) is a functional imaging technique of nuclear medicine which enables in vivo visualization of numerous biological molecules expressed in several human tissues. Brain PET is most powerful to study in vivo neuronal and glial cells function as well as cerebral blood flow in a plethora of neurodegenerative disorders including Parkinson's disease, Alzheimer's and HD. In absence of HD-specific biomarkers for monitoring disease progression, previous PET studies in HD were merely focused on the study of dopaminergic terminals, cerebral blood flow and glucose metabolism in manifest and premanifest HD-gene carriers. More recently, research interest has been exploring novel PET targets in HD including the state of phosphodiesterse expression and the role of activated microglia. Hence, a better understanding of the HD pathogenesis mechanisms may lead to the development of targeted therapies. PET imaging follow-up studies with novel selective PET radiotracers such as 11C-IMA-107 and 11C-PBR28 may provide insight on disease progression and identify prognostic biomarkers, elucidate the underlying HD pathology and assess novel pharmaceutical agents and over time.

[(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats.

PubMed

Bascuñana, Pablo; Javela, Julián; Delgado, Mercedes; Fernández de la Rosa, Rubén; Shiha, Ahmed Anis; García-García, Luis; Pozo, Miguel Ángel

2016-10-01

Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET

PubMed Central

Rockne, Russell C.; Trister, Andrew D.; Jacobs, Joshua; Hawkins-Daarud, Andrea J.; Neal, Maxwell L.; Hendrickson, Kristi; Mrugala, Maciej M.; Rockhill, Jason K.; Kinahan, Paul; Krohn, Kenneth A.; Swanson, Kristin R.

2015-01-01

Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient's disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [18F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning. PMID:25540239

5-HT2 receptor distribution shown by [18F] setoperone PET in high-functioning autistic adults.

PubMed

Beversdorf, David Q; Nordgren, Richard E; Bonab, Ali A; Fischman, Alan J; Weise, Steven B; Dougherty, Darin D; Felopulos, Gretchen J; Zhou, Feng C; Bauman, Margaret L

2012-01-01

The serotonergic system is implicated in disordered emotional behavior. Autism is characterized by impaired processing of emotional information. The serotonergic (5-HT) system is also critically involved in brain development, and abnormal brain synthesis of serotonin is observed in autism. Furthermore, whole blood and platelet serotonin have been reported to be elevated in autism. The authors examined the CNS serotonin system in autism in vivo. 5-HT2 receptors were visualized by PET imaging of [18F]setoperone-binding in this pilot study of 6 high-functioning autistic adults and 10 matched-control participants. Autism subjects had less thalamic [18F]setoperone binding than controls, when covaried for age, but no difference reached significance in other areas. A negative relationship between thalamic binding and history of language impairment was also observed. Further studies will be needed to gain a clearer picture of the role of the 5-HT system in autism.

Discovery of a highly selective glycogen synthase kinase-3 inhibitor (PF-04802367) that modulates tau phosphorylation in brain: Translation for PET neuroimaging

PubMed Central

Liang, Steven H.; Chen, Jinshan Michael; Normandin, Marc D.; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Trapa, Patrick; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Lefker, Bruce A.; Enerson, Bradley E.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas; Patnaik, Debasis; Wagner, Florence F.; Perlis, Roy; Holson, Edward B.; Haggarty, Stephen J.; Fakhri, Georges El

2016-01-01

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology and neurology. We have identified N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. We demonstrated its efficacy in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A 11C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. PMID:27355874

The current status of positron emission tomography.

PubMed

Digby, W; Keppler, J

2000-01-01

Positron emission tomography (PET), invented over 25 years ago, is the only imaging technique that provides images of the biological basis of disease. Since disease is a biological process, PET routinely detects disease when other imaging studies, such as CT and MRI, are normal. In addition to its clinical effectiveness, PET has been shown to reduce costs, primarily due to the elimination of other less accurate diagnostic tests and ineffective surgeries. PET has been determined to be applicable to a number of specific applications in the areas of: imaging cancer patients, characterizing myocardial blood flow and viability, and brain imaging in various physiological and pathologic conditions. Tremendous progress has been made in resolving the regulatory and reimbursement issues facing the field of PET. Working with HCFA, representatives of the Institute for Clinical PET and the Society of Nuclear Medicine have brought about expanded HCFA coverage for PET. When HCFA first authorized payment for PET, all coverage decisions were restricted to HCFA and an expanded national coverage policy. HCFA revised its national coverage policy in 1997; this was the first of several steps taken by HCFA towards careful expansion of PET reimbursement. In March 1999, three new indications for whole-body PET scans were added to Medicare's coverage policy. The Institute for Clinical PET is continuing to work with HCFA on continued, appropriate expansion of the coverage policy. This article is partially excerpted from a written statement made by Terry Douglass, Ph.D., president of CTI, Inc., on May 12, 1999, before the Senate Committee on Commerce, Science and Transportation and its Subcommittee on Science, Technology and Space. This was part of the committee's study of "Emerging Technologies in the New Millennium."

Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis.

PubMed

Nakayama, N; Okumura, A; Shinoda, J; Nakashima, T; Iwama, T

2006-07-01

The cerebral metabolism of patients in the chronic stage of traumatic diffuse brain injury (TDBI) has not been fully investigated. To study the relationship between regional cerebral metabolism (rCM) and consciousness disturbance in patients with TDBI. 52 patients with TDBI in the chronic stage without large focal lesions were enrolled, and rCM was evaluated by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with statistical parametric mapping (SPM). All the patients were found to have disturbed consciousness or cognitive function and were divided into the following three groups: group A (n = 22), patients in a state with higher brain dysfunction; group B (n = 13), patients in a minimally conscious state; and group C (n = 17), patients in a vegetative state. rCM patterns on FDG-PET among these groups were evaluated and compared with those of normal control subjects on statistical parametric maps. Hypometabolism was consistently indicated bilaterally in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus. Hypometabolism in these regions was the most widespread and prominent in group C, and that in group B was more widespread and prominent than that in group A. Bilateral hypometabolism in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus may reflect the clinical deterioration of TDBI, which is due to functional and structural disconnections of neural networks rather than due to direct cerebral focal contusion.

Clinical, Dopaminergic, and Metabolic Correlations in Parkinson Disease: A Dual-Tracer PET Study.

PubMed

Liu, Feng-Tao; Ge, Jing-Jie; Wu, Jian-Jun; Wu, Ping; Ma, Yilong; Zuo, Chuan-Tao; Wang, Jian

2018-05-31

Neuroimaging indicators of Parkinson disease have been developed and applied in clinical practices. Dopaminergic imaging reflects nigrostriatal dopaminergic dysfunction, and metabolic network imaging offers disease-related metabolic changes at a system level. We aimed to elucidate the association between Parkinsonian symptoms and neuroimaging, and interactions between different imaging techniques. We conducted a dual-tracer PET study for the combined assessments of dopaminergic binding (C-CFT) and glucose metabolism (F-FDG) in 103 participants with Parkinson disease (65 male and 38 female subjects). The detailed clinical rating scores were systematically collected in all members. The interactions among dopaminergic bindings, metabolic changes, and clinical manifestations were evaluated at voxel, regional, and network levels. Striatal DAT binding correlated with akinesia-rigidity (P < 0.001) but not with tremor; the metabolic PET imaging, nonspecific to the dopaminergic dysfunction, disclosed a set of brain regions correlating with the cardinal symptoms, including tremor. In addition, the unilateral symptom correlated with the contralateral nigrostriatal dopamine loss, but with bilateral metabolic changes, suggesting their differences in the application of disease-related mechanistic studies. Further imaging-imaging correlation study revealed that dopaminergic dysfunction correlated with widely distributed metabolic changes in Parkinson disease, and the modest correlations supported the findings on the clinical-imaging correlation. In this dual-tracer PET study, we demonstrated the robust interactions among dopaminergic dysfunction, metabolic brain changes and clinical manifestations at voxel, regional, and network levels. Our findings might promote the understanding in the proper application of dopaminergic and metabolic PET imaging in Parkinson disease and offer more evidence in support of Parkinsonian pathophysiological mechanisms.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Evaluation of [11C]TAZA for amyloid β plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT.

PubMed

Pan, Min-Liang; Mukherjee, Meenakshi T; Patel, Himika H; Patel, Bhavin; Constantinescu, Cristian C; Mirbolooki, M Reza; Liang, Christopher; Mukherjee, Jogeshwar

2016-04-01

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11)C]TAZA), for binding to Aβ plaques in postmortem human brain (AD and normal control (NC)). Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aβ plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/μmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Aβ plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. [(11)C]TAZA exhibited high binding to Aβ plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. © 2016 Wiley Periodicals, Inc.

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.

Optimized MLAA for quantitative non-TOF PET/MR of the brain

NASA Astrophysics Data System (ADS)

Benoit, Didier; Ladefoged, Claes N.; Rezaei, Ahmadreza; Keller, Sune H.; Andersen, Flemming L.; Højgaard, Liselotte; Hansen, Adam E.; Holm, Søren; Nuyts, Johan

2016-12-01

For quantitative tracer distribution in positron emission tomography, attenuation correction is essential. In a hybrid PET/CT system the CT images serve as a basis for generation of the attenuation map, but in PET/MR, the MR images do not have a similarly simple relationship with the attenuation map. Hence attenuation correction in PET/MR systems is more challenging. Typically either of two MR sequences are used: the Dixon or the ultra-short time echo (UTE) techniques. However these sequences have some well-known limitations. In this study, a reconstruction technique based on a modified and optimized non-TOF MLAA is proposed for PET/MR brain imaging. The idea is to tune the parameters of the MLTR applying some information from an attenuation image computed from the UTE sequences and a T1w MR image. In this MLTR algorithm, an {αj} parameter is introduced and optimized in order to drive the algorithm to a final attenuation map most consistent with the emission data. Because the non-TOF MLAA is used, a technique to reduce the cross-talk effect is proposed. In this study, the proposed algorithm is compared to the common reconstruction methods such as OSEM using a CT attenuation map, considered as the reference, and OSEM using the Dixon and UTE attenuation maps. To show the robustness and the reproducibility of the proposed algorithm, a set of 204 [18F]FDG patients, 35 [11C]PiB patients and 1 [18F]FET patient are used. The results show that by choosing an optimized value of {αj} in MLTR, the proposed algorithm improves the results compared to the standard MR-based attenuation correction methods (i.e. OSEM using the Dixon or the UTE attenuation maps), and the cross-talk and the scale problem are limited.

Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

PubMed

Salabert, Anne-Sophie; Vaysse, Laurence; Beaurain, Marie; Alonso, Mathieu; Arribarat, Germain; Lotterie, Jean-Albert; Loubinoux, Isabelle; Tafani, Mathieu; Payoux, Pierre

2017-01-01

Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression. A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo. Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft. The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection.

Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease

PubMed Central

Zetterberg, Henrik; Mattsson, Niklas; Johansson, Per; Minthon, Lennart; Blennow, Kaj; Olsson, Mattias

2015-01-01

Objective: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). Methods: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study. Results: The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93–0.94). The best PET measures performed similarly (AUC 0.92–0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03–0.12, p < 0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. Conclusions: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. Classification of evidence: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately. PMID:26354982

Extracranial bone metastases from recurrent anaplastic astrocytoma on FDG PET/CT

PubMed Central

Li, Zu-Gui; Mu, Hai-Yu

2017-01-01

Abstract Objective: Extracranial bone metastases from astrocytoma are rare and frequently detected as part of multiorgan metastases. It is extremely rare for astrocytoma to have extracranial bone metastases alone. The importance of whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in evaluating extracranial metastasis (ECMs) has not been described effectively due to the rarity of this event. The purpose of our case report is to emphasize the role of FDG PET/CT in the assessment of tumor recurrence and extracranial bone metastases from anaplastic astrocytoma. Methods and materials: A 25-year-old woman was firstly admitted with a 4-month history of progressive blurred vision, and 2-month history of intermittent headache. Presurgical MRI imaging revealed a large mass in the left trigone of lateral ventricle. Subsequently, she underwent tumor resection, radiotherapy and chemotherapy. A final pathological diagnosis of anaplastic astrocytoma (WHO III) was made. Nearly 12 months after the surgery, the follow-up brain MR imaging revealed a contrast-enhanced lesion in the site of operative region. Whole-body FDG PET/CT imaging was performed to evaluate the situation. Results: Postoperative brain FDG PET/CT showed an abnormal focal FDG uptake corresponding to the contrast-enhanced lesion in the operative area, suggesting a tumor recurrence. Whole-body FDG PET/CT also showed multiple FDG-avid osteosclerotic lesions in the body. It was highly suggestive of extracranial bone metastases. A subsequent open bone biopsy of FDG-avid lesion in right iliac crest was performed. Histopathological and immunohistochemical findings indicated characteristic of glioma. The patient died 1 month later, nearly 13 months after the initial diagnosis. Conclusions: ECMs from anaplastic astrocytoma are extremely rare but they do occur. Whole-body FDG PET/CT imaging with inclusion of brain was valuable in differentiating tumor recurrence from radiation necrosis and in detecting uncommon extracranial bone metastases from anaplastic astrocytoma, which were closely related to prognosis of this disease. PMID:28591062

Brain correlates of stuttering and syllable production. A PET performance-correlation analysis.

PubMed

Fox, P T; Ingham, R J; Ingham, J C; Zamarripa, F; Xiong, J H; Lancaster, J L

2000-10-01

To distinguish the neural systems of normal speech from those of stuttering, PET images of brain blood flow were probed (correlated voxel-wise) with per-trial speech-behaviour scores obtained during PET imaging. Two cohorts were studied: 10 right-handed men who stuttered and 10 right-handed, age- and sex-matched non-stuttering controls. Ninety PET blood flow images were obtained in each cohort (nine per subject as three trials of each of three conditions) from which r-value statistical parametric images (SPI¿r¿) were computed. Brain correlates of stutter rate and syllable rate showed striking differences in both laterality and sign (i.e. positive or negative correlations). Stutter-rate correlates, both positive and negative, were strongly lateralized to the right cerebral and left cerebellar hemispheres. Syllable correlates in both cohorts were bilateral, with a bias towards the left cerebral and right cerebellar hemispheres, in keeping with the left-cerebral dominance for language and motor skills typical of right-handed subjects. For both stutters and syllables, the brain regions that were correlated positively were those of speech production: the mouth representation in the primary motor cortex; the supplementary motor area; the inferior lateral premotor cortex (Broca's area); the anterior insula; and the cerebellum. The principal difference between syllable-rate and stutter-rate positive correlates was hemispheric laterality. A notable exception to this rule was that cerebellar positive correlates for syllable rate were far more extensive in the stuttering cohort than in the control cohort, which suggests a specific role for the cerebellum in enabling fluent utterances in persons who stutter. Stutters were negatively correlated with right-cerebral regions (superior and middle temporal gyrus) associated with auditory perception and processing, regions which were positively correlated with syllables in both the stuttering and control cohorts. These findings support long-held theories that the brain correlates of stuttering are the speech-motor regions of the non-dominant (right) cerebral hemisphere, and extend this theory to include the non-dominant (left) cerebellar hemisphere. The present findings also indicate a specific role of the cerebellum in the fluent utterances of persons who stutter. Support is also offered for theories that implicate auditory processing problems in stuttering.

Benzodiazepine site pharmacokinetic/pharmacodynamic quantification in man: direct measurement of drug occupancy and effects on the human brain in vivo.

PubMed

Malizia, A L; Gunn, R N; Wilson, S J; Waters, S H; Bloomfield, P M; Cunningham, V J; Nutt, D J

1996-01-01

To date, the study of the relationship between drug occupancy and action in the brain has had to rely on the use of either animal models or of indirect kinetic measures in man, e.g. serum concentrations of unbound drug (as a measure of "free" drug in brain). We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man. Five healthy volunteers each had two PET scans using [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a study investigating kinetic models and the relationship between occupancy and effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was displaced from the brain by infusion of midazolam administered i.v. 30 min into the scan. In one study a higher dose of midazolam was administered than in the other (range 12.5-50 micrograms/kg). Time-activity curves of the concentration of radioligand were derived in 17 different brain regions using a stereotactic automatic method of region selection. We demonstrated that there are significant differences in an index of occupancy, induced by the two different doses of midazolam, both across brain regions and within subjects. There was a significant correlation between measured occupancy index change and pharmacodynamic effects as measured by the peak change in beta 1 spectral power on EEG. There was no significant correlation between dose administered and EEG changes; plasma concentrations of midazolam were correlated with the occupancy index and with the EEG measures. In addition, we have demonstrated that a non-regional total index of brain occupancy can be obtained by analysing the non-tomographic data obtained with the PET scanner (total radioactivity counts head curve) and that this index shows significant correlations both with the dose administered and with the pharmacodynamic measure. This last finding validates the use of other non-tomographic counting techniques (Malizia et al., 1995a) where an index of displacement can be obtained after the administration of less than 1% of the dose of radiation needed for a PET study. These studies are likely to be useful in human psychopharmacology, in particular in the assessment of tolerance and of putative changes in benzodiazepine sensitivity in anxiety disorders. The same principles can be applied to other ligand studies and will be useful to validate current PK/PD models.

Visualizing the anatomical-functional correlation of the human brain

NASA Astrophysics Data System (ADS)

Chang, YuKuang; Rockwood, Alyn P.; Reiman, Eric M.

1995-04-01

Three-dimensional tomographic images obtained from different modalities or from the same modality at different times provide complementary information. For example, while PET shows brain function, images from MRI identify anatomical structures. In this paper, we investigate the problem of displaying available information about structures and function together. Several steps are described to achieve our goal. These include segmentation of the data, registration, resampling, and display. Segmentation is used to identify brain tissue from surrounding tissues, especially in the MRI data. Registration aligns the different modalities as closely as possible. Resampling arises from the registration since two data sets do not usually correspond and the rendering method is most easily achieved if the data correspond to the same grid used in display. We combine several techniques to display the data. MRI data is reconstructed from 2D slices into 3D structures from which isosurfaces are extracted and represented by approximating polygonalizations. These are then displayed using standard graphics pipelines including shaded and transparent images. PET data measures the qualitative rates of cerebral glucose utilization or oxygen consumption. PET image is best displayed as a volume of luminous particles. The combination of both display methods allows the viewer to compare the functional information contained in the PET data with the anatomically more precise MRI data.

[18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

PubMed Central

Sarwal, A.; Hantus, S.

2016-01-01

Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed. PMID:27559482

Estimation of position resolution for DOI-PET detector using diameter 0.2 mm WLS fibers

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

Kaneko, Naomi; Ito, Hiroshi; Kawai, Hideyuki

We have been developing sub mm resolution andmore » $$ 1 million DOI-PET detector using wavelength shifting fibers (WLSF), scintillation crystals of plate shape and SiPM (MPPC: HAMAMATSU K. K.). Conventional design of DOI-PET detector is obtained about mm{sup 3} of resolution by using some blocks detecting gamma-ray in mm 3 voxel. It requires the production cost of $$ a few ten million or more for high technique of processing crystal and a lot of number of photo-devices, and this technology is reaching the limit of the resolution. Both higher resolution and lower cost of DOI-PET detector production is challenging for PET diagnosis population. We propose two type of detector. One is a whole body PET system, and the other for brain or small animal. Both PET system consist 6 blocks. the former consist of 6 layers 300 mm x 300 mm x 4 mm crystal plate. The latter consist 16 crystal layers, 4 x 4 crystal array. The size of crystal plate is 40 mm x 40 mm x 1 mm.The WLSF sheets connect to upper and lower plane. The whole PET systems connect 8 SiPMs are bonded on each side. For the brain PET, 9 WLSF fibers are bond on the each side. The expected position resolution maybe less than 1 mm at the former. We have estimation experimental performance the system using {sup 22}Na radioactive source. The collection efficiency of WLSF (R-3) sheet was achieved 10% with GAGG at 511 keV. The relation between reconstruction position and incident position is obtained linearity and achieved the resolution of 0.7 mm FWHM for x-axis of DOI by readout WLSF. (authors)« less

Characterization of brain mGluR5 binding in a pilot study of late-life major depressive disorder using positron emission tomography and [11C]ABP688

PubMed Central

DeLorenzo, C; Sovago, J; Gardus, J; Xu, J; Yang, J; Behrje, R; Kumar, J S D; Devanand, D P; Pelton, G H; Mathis, C A; Mason, N S; Gomez-Mancilla, B; Aizenstein, H; Mann, J J; Parsey, R V

2015-01-01

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in the pathophysiology of mood and anxiety disorders and is a potential treatment target in major depressive disorder (MDD). This study compared brain mGluR5 binding in elderly patients suffering from MDD with that in elderly healthy volunteers using positron emission tomography (PET) and [11C]ABP688. Twenty elderly (mean age: 63.0±6.3) subjects with MDD and twenty-two healthy volunteers in the same age range (mean age: 66.4±7.3) were examined with PET after a single bolus injection of [11C]ABP688, with many receiving arterial sampling. PET images were analyzed on a region of interest and a voxel level to compare mGluR5 binding in the brain between the two groups. Differences in [11C]ABP688 binding between patients with early- and late-onset depression were also assessed. In contrast to a previously published report in a younger cohort, no significant difference in [11C]ABP688 binding was observed between elderly subjects with MDD and healthy volunteers. [11C]ABP688 binding was also similar between subgroups with early- or late-onset depression. We believe this is the first study to examine mGluR5 expression in depression in the elderly. Although future work is required, results suggest potential differences in the pathophysiology of elderly depression versus depression earlier in life. PMID:26645628

[Correlation of auditory-verbal skills in patients with cochlear implants and their evaluation in positone emission tomography (PET)].

PubMed

Łukaszewicz, Zuzanna; Soluch, Paweł; Niemczyk, Kazimierz; Lachowska, Magdalena

2010-06-01

An assumption was taken that in central nervous system (CNS) in patients above 15 years of age there are possible mechanisms of neuronal changes. Those changes allow for reconstruction or formation of natural activation pattern of appropriate brain structures responsible for auditory speech processing. The aim of the study was to observe if there are any dynamic functional changes in central nervous system and their correlation to the auditory-verbal skills of the patients. Nine right-handed patients between 15 and 36 years of age were examined, 6 females and 3 males. All of them were treated with cochlear implantation and are in frequent follow-up in the Department of Otolaryngology at the Medical University of Warsaw due to profound sensorineural hearing loss. In present study the patients were examined within 24 hours after the first fitting of the speech processor of the cochlear implant, and 1 and 2 years subsequently. Combination of performed examinations consisted of: positone emission tomography of the brain, and audiological tests including speech assessment. In the group of patients 4 were postlingually deaf, and 5 were prelinqually deaf. Postlingually deaf patients achieved great improvement of hearing and speech understanding. In their first PET examination very intensive activation of visual cortex V1 and V2 (BA17 and 18) was observed. There was no significant activation in the dominant (left) hemisphere of the brain. In PET examination performed 1 and 2 years after the cochlear implantation no more V1 and V2 activation region was observed. Instead particular regions of the left hemisphere got activated. In prelingually deaf patients no significant changes in central nervous system were noticeable neither in PET nor in speech assessment, although their hearing possibilities improved. Positive correlation was observed between the level of speech understanding, linguistic skills and the activation of appropriate areas of the left hemisphere of the brain in postlingually deaf patients treated with cochlear implants. No such correlation was noted in prelingualy patients treated with the same method.

Characterization of the radioactive metabolites of the 5-HT1A receptor radioligand, [O-methyl-11C]WAY-100635, in monkey and human plasma by HPLC: comparison of the behaviour of an identified radioactive metabolite with parent radioligand in monkey using PET.

PubMed

Osman, S; Lundkvist, C; Pike, V W; Halldin, C; McCarron, J A; Swahn, C G; Ginovart, N; Luthra, S K; Bench, C J; Grasby, P M; Wikström, H; Barf, T; Cliffe, I A; Fletcher, A; Farde, L

1996-07-01

N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), labelled in the O-methyl group with carbon-11 (t1/2 = 20.4 min), is a promising radioligand for application with positron emission tomography (PET) to the study of 5-HT1A receptors in living human brain. An understanding of the metabolism of this new radioligand is crucial to the development of a biomathematical model for the interpretation of the kinetics of radioactivity uptake in brain in terms of receptor-binding parameters. After intravenous injection of [O-methyl-11C]WAY-100635 into humans, radioactivity was found to clear rapidly from blood and plasma. By using established methods for the analysis of radioactivity in plasma, it was found that intravenously injected [O-methyl-11C]WAY-100635 is rapidly metabolised to more polar radioactive compounds in a cynomolgus monkey and in humans. Thus, at 60 min postinjection, parent radioligand represented 40% and 5% of the radioactivity in monkey and human plasma, respectively. In monkey and human, one of the radioactive metabolites was identified as the descyclohexanecarbonyl analogue of the parent radioligand, namely [O-methyl-11C]WAY-100634. This compound is known to have high affinity for 5-HT1A receptors and alpha 1-adrenoceptors. In a PET experiment it was demonstrated that, after IV injection of [O-methyl-11C]WAY-100634 into a cynomolgus monkey, radioactivity was avidly taken up by brain. Uptake of radioactivity was higher in 5-HT1A receptor-rich frontal cortex than in cerebellum, which is devoid of 5-HT1A receptors. Polar radioactive metabolites appeared in plasma. The results suggest that the use of WAY-100635 labelled with carbon-11 in its cyclohexanecarbonyl moiety may provide enhanced signal contrast in PET studies and a possibility to develop a simple biomathematical model for regional brain radioactivity uptake.

DEVELOPMENT OF AUTOMATED SOFTWARE PROGRAM FOR THE ANALYSIS OF ALZHEIMER'S DISEASE BETA-AMYLOID SCANS

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

Mariotti, Jack; Zubal, George

2013-12-18

Study goal: A Phase 1 evaluation of the kinetics, clearance and cerebral distribution of one novel peripheral benzodiazepine receptors(PBR)positron emission tomography (PET) imaging agent, 18F-PBR-111 following intravenous administration in healthy volunteers and Alzheimer's disease (AD) patients. Short title: Evaluation of PET imaging with PBR-111 in HV and AD subjects Proof of Mechanism. Primary Objective: To evaluate the cerebral distribution of PBR-111 positron emission tomography (PET) for detection/exclusion of microglial activation in patients with Alzheimer's disease subjects compared to healthy volunteers. Secondary objectives: - To assess the dynamic uptake and washout of [18F]PBR-111, a potential imaging bio-marker for inflammatory changes inmore » brain, using positron emission tomography in subjects with Alzheimer's disease (AD) and healthy volunteers (HV). - To perform blood metabolite characterization of [18F]PBR-111 in subjects with AD and HV to determine the nature of metabolites in assessment of [18F]-PBR-111 as a PET brain imaging agent. Name of radioactive drug substance: PBR-111 Dose(s): The applied PBR-111 radioactive dose will be up to 5.0 mCi, diluted in a maximum of 10 ml of saline. The radioligand will be administered as a slow intravenous bolus injection (i.e., 6 sec/ml) into a large vein (e.g., antecubital vein). Route of administration: Intravenous injection Duration of treatment: Single administration of a diagnostic agent Indication: PBR-111 positron emission tomography (PET) imaging has the potential to detect microglial activation. In the presence of PBR-111 uptake (representative of microglial activation), inflammation in the brain can be detected. Diagnosis and main criteria for inclusion: Study participants will be HVs and patients diagnosed with probable AD. HVs must be 18 years of age (at least four subjects 50 years of age) and have no evidence of cognitive impairment or other neurologic disease by medical history. The lack of cognitive impairment will also be based on a Clinical Dementia Rating (CDR) of 0. Patients with probable AD must be 50 years of age and must fulfill the National Institute of Neurological and Communicative Disorders and Stroke, Alzheimer's Disease and Related Disorders Association [NINCDS-ADRDA] criteria for probable AD. The CDR score must be 1.0 and 2.0 and have a modified Hachinski of 4. All HVs and all patients with probable AD must be able to comply with all study procedures. Study design: This is a Phase 1, open-label, single-center, non-randomized single dose study to assess the kinetics, clearance and cerebral distribution of PBR-111 PET imaging in detecting microglial activation in the brain in patients with probable AD compared to HVs. All aspects related to image acquisition, processing, and visual as well as quantitative evaluation will be developed, optimized, and validated (where required). Each subject will be required to visit the study center during the screening phase and on the PBR-111 PET imaging day (baseline). A telephone follow-up visit will be performed 7 days (± 3 days) after PBR-111 PET administration. At the screening visit, each subject (or caregiver in the case of AD subjects) will be asked to provide written informed consent or assent. During the screening phase (maximum duration of 60 days) subject medical, neurological, and surgical history, clinical assessments, and a neuro-psychiatric evaluation will be performed on all eligible subjects. Subjects will be allowed to leave the center after all evaluations have been completed. During this period an MRI of the brain will be performed during the screening period. If an MRI of the brain has been performed within six months of the imaging visit using the methods described in the protocol, and there has been no medically significant events in the interim, the previous MRI may be used. During the PBR-111 PET imaging day, all subjects will receive a single intravenous injection of PBR-111 and scanning will be performed over a 3.5 hour period. Each subject will have a telephone follow-up 7 days (± 3 days) thereafter to assess for adverse events. Methodology: - Assessments to provide clinical characterization of the AD subjects will be performed. - After administration of PBR-111, images will be generated with state-of-the-art PET imaging. Images will be assessed quantitatively for the presence of microglial activation by a nuclear physician blinded to clinical data. - Total radioactivity and estimation of the fraction of radioactivity associated to the un-metabolized tracer will be determined. In addition, the metabolite patterns of PBR-111 are determined in venous plasma and arterial samples based on high-performance liquid chromatography (HPLC) analyses. - Arterial sampling will be acquired in the initial two AD and two HV subjects and modeling will be assessed to determine if additional arterial sampling is necessary.« less

Efficient system modeling for a small animal PET scanner with tapered DOI detectors.

PubMed

Zhang, Mengxi; Zhou, Jian; Yang, Yongfeng; Rodríguez-Villafuerte, Mercedes; Qi, Jinyi

2016-01-21

A prototype small animal positron emission tomography (PET) scanner for mouse brain imaging has been developed at UC Davis. The new scanner uses tapered detector arrays with depth of interaction (DOI) measurement. In this paper, we present an efficient system model for the tapered PET scanner using matrix factorization and a virtual scanner geometry. The factored system matrix mainly consists of two components: a sinogram blurring matrix and a geometrical matrix. The geometric matrix is based on a virtual scanner geometry. The sinogram blurring matrix is estimated by matrix factorization. We investigate the performance of different virtual scanner geometries. Both simulation study and real data experiments are performed in the fully 3D mode to study the image quality under different system models. The results indicate that the proposed matrix factorization can maintain image quality while substantially reduce the image reconstruction time and system matrix storage cost. The proposed method can be also applied to other PET scanners with DOI measurement.

Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas.

PubMed

Pyka, Thomas; Gempt, Jens; Hiob, Daniela; Ringel, Florian; Schlegel, Jürgen; Bette, Stefanie; Wester, Hans-Jürgen; Meyer, Bernhard; Förster, Stefan

2016-01-01

Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not hold in multivariate analysis. Determination of uptake heterogeneity in pre-therapeutic FET-PET using textural features proved valuable for the (sub-)grading of high-grade glioma as well as prediction of tumor progression and patient survival, and showed improved performance compared to standard parameters such as TBR and tumor volume. Our results underscore the importance of intratumoral heterogeneity in the biology of high-grade glial cell tumors and may contribute to individual therapy planning in the future, although they must be confirmed in prospective studies before incorporation into clinical routine.

Interim 18F-FGD PET/CT may not predict the outcome in primary central nervous system lymphoma patients treated with sequential treatment with methotrexate and cytarabine.

PubMed

Jo, Jae-Cheol; Yoon, Dok Hyun; Kim, Shin; Lee, Kyoungmin; Kang, Eun Hee; Park, Jung Sun; Ryu, Jin-Sook; Huh, Jooryung; Park, Chan-Sik; Kim, Jong Hoon; Lee, Sang Wook; Suh, Cheolwon

2017-09-01

18 F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17-75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.

Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography.

PubMed

Toyama, Hiroshi; Ichise, Masanori; Liow, Jeih-San; Modell, Kendra J; Vines, Douglass C; Esaki, Takanori; Cook, Michelle; Seidel, Jurgen; Sokoloff, Louis; Green, Michael V; Innis, Robert B

2004-08-01

The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMR(glc)) in mice by use of (18)F-FDG and a small animal PET scanner. rCMR(glc) determined with (18)F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-(14)C-DG method. In addition, we compared the rCMR(glc) values under isoflurane, ketamine and xylazine anesthesia, and awake states. Immediately after injection of (18)F-FDG and 2-(14)C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of (18)F-FDG and 2-(14)C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-(14)C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal (18)F-FDG PET and 2-(14)C-DG autoradiographic images. rCMR(glc) values were calculated for both tracers by the autoradiographic 2-(14)C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Average rCMR(glc) values in cerebral cortex with (18)F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-(14)C-DG (r(2) = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMR(glc) values with (18)F-FDG PET were higher (by 17.3%) than those with 2-(14)C-DG. Values for rCMR(glc) and uptake (percentage injected dose per gram [%ID/g]) with (18)F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMR(glc) were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of (18)F-FDG and glucose uptake to the brain under hyperglycemia. We were able to obtain accurate absolute quantification of rCMR(glc) with mouse (18)F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-(14)C-DG method. Underestimation of rCMR(glc) by (18)F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMR(glc) from (18)F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for (18)F-FDG.

Comparison of manual and automatic techniques for substriatal segmentation in 11C-raclopride high-resolution PET studies.

PubMed

Johansson, Jarkko; Alakurtti, Kati; Joutsa, Juho; Tohka, Jussi; Ruotsalainen, Ulla; Rinne, Juha O

2016-10-01

The striatum is the primary target in regional C-raclopride-PET studies, and despite its small volume, it contains several functional and anatomical subregions. The outcome of the quantitative dopamine receptor study using C-raclopride-PET depends heavily on the quality of the region-of-interest (ROI) definition of these subregions. The aim of this study was to evaluate subregional analysis techniques because new approaches have emerged, but have not yet been compared directly. In this paper, we compared manual ROI delineation with several automatic methods. The automatic methods used either direct clustering of the PET image or individualization of chosen brain atlases on the basis of MRI or PET image normalization. State-of-the-art normalization methods and atlases were applied, including those provided in the FreeSurfer, Statistical Parametric Mapping8, and FSL software packages. Evaluation of the automatic methods was based on voxel-wise congruity with the manual delineations and the test-retest variability and reliability of the outcome measures using data from seven healthy male participants who were scanned twice with C-raclopride-PET on the same day. The results show that both manual and automatic methods can be used to define striatal subregions. Although most of the methods performed well with respect to the test-retest variability and reliability of binding potential, the smallest average test-retest variability and SEM were obtained using a connectivity-based atlas and PET normalization (test-retest variability=4.5%, SEM=0.17). The current state-of-the-art automatic ROI methods can be considered good alternatives for subjective and laborious manual segmentation in C-raclopride-PET studies.

A small animal PET based on GAPDs and charge signal transmission approach for hybrid PET-MR imaging

NASA Astrophysics Data System (ADS)

Kang, Jihoon; Choi, Yong; Hong, Key Jo; Hu, Wei; Jung, Jin Ho; Huh, Yoonsuk; Kim, Byung-Tae

2011-08-01

Positron emission tomography (PET) employing Geiger-mode avalanche photodiodes (GAPDs) and charge signal transmission approach was developed for small animal imaging. Animal PET contained 16 LYSO and GAPD detector modules that were arranged in a 70 mm diameter ring with an axial field of view of 13 mm. The GAPDs charge output signals were transmitted to a preamplifier located remotely using 300 cm flexible flat cables. The position decoder circuits (PDCs) were used to multiplex the PET signals from 256 to 4 channels. The outputs of the PDCs were digitized and further-processed in the data acquisition unit. The cross-compatibilities of the PET detectors and MRI were assessed outside and inside the MRI. Experimental studies of the developed full ring PET were performed to examine the spatial resolution and sensitivity. Phantom and mouse images were acquired to examine the imaging performance. The mean energy and time resolution of the PET detector were 17.6% and 1.5 ns, respectively. No obvious degradation on PET and MRI was observed during simultaneous PET-MRI data acquisition. The measured spatial resolution and sensitivity at the CFOV were 2.8 mm and 0.7%, respectively. In addition, a 3 mm diameter line source was clearly resolved in the hot-sphere phantom images. The reconstructed transaxial PET images of the mouse brain and tumor displaying the glucose metabolism patterns were imaged well. These results demonstrate GAPD and the charge signal transmission approach can allow the development of high performance small animal PET with improved MR compatibility.

PET Imaging of Tau Deposition in the Aging Human Brain

PubMed Central

Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry D.; Rabinovici, Gil D.; Jagust, William J.

2016-01-01

SUMMARY Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid, and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition. PMID:26938442

Sparsity-constrained PET image reconstruction with learned dictionaries

NASA Astrophysics Data System (ADS)

Tang, Jing; Yang, Bao; Wang, Yanhua; Ying, Leslie

2016-09-01

PET imaging plays an important role in scientific and clinical measurement of biochemical and physiological processes. Model-based PET image reconstruction such as the iterative expectation maximization algorithm seeking the maximum likelihood solution leads to increased noise. The maximum a posteriori (MAP) estimate removes divergence at higher iterations. However, a conventional smoothing prior or a total-variation (TV) prior in a MAP reconstruction algorithm causes over smoothing or blocky artifacts in the reconstructed images. We propose to use dictionary learning (DL) based sparse signal representation in the formation of the prior for MAP PET image reconstruction. The dictionary to sparsify the PET images in the reconstruction process is learned from various training images including the corresponding MR structural image and a self-created hollow sphere. Using simulated and patient brain PET data with corresponding MR images, we study the performance of the DL-MAP algorithm and compare it quantitatively with a conventional MAP algorithm, a TV-MAP algorithm, and a patch-based algorithm. The DL-MAP algorithm achieves improved bias and contrast (or regional mean values) at comparable noise to what the other MAP algorithms acquire. The dictionary learned from the hollow sphere leads to similar results as the dictionary learned from the corresponding MR image. Achieving robust performance in various noise-level simulation and patient studies, the DL-MAP algorithm with a general dictionary demonstrates its potential in quantitative PET imaging.

Cerebral blood flow with [15O]water PET studies using an image-derived input function and MR-defined carotid centerlines

NASA Astrophysics Data System (ADS)

Fung, Edward K.; Carson, Richard E.

2013-03-01

Full quantitative analysis of brain PET data requires knowledge of the arterial input function into the brain. Such data are normally acquired by arterial sampling with corrections for delay and dispersion to account for the distant sampling site. Several attempts have been made to extract an image-derived input function (IDIF) directly from the internal carotid arteries that supply the brain and are often visible in brain PET images. We have devised a method of delineating the internal carotids in co-registered magnetic resonance (MR) images using the level-set method and applying the segmentations to PET images using a novel centerline approach. Centerlines of the segmented carotids were modeled as cubic splines and re-registered in PET images summed over the early portion of the scan. Using information from the anatomical center of the vessel should minimize partial volume and spillover effects. Centerline time-activity curves were taken as the mean of the values for points along the centerline interpolated from neighboring voxels. A scale factor correction was derived from calculation of cerebral blood flow (CBF) using gold standard arterial blood measurements. We have applied the method to human subject data from multiple injections of [15O]water on the HRRT. The method was assessed by calculating the area under the curve (AUC) of the IDIF and the CBF, and comparing these to values computed using the gold standard arterial input curve. The average ratio of IDIF to arterial AUC (apparent recovery coefficient: aRC) across 9 subjects with multiple (n = 69) injections was 0.49 ± 0.09 at 0-30 s post tracer arrival, 0.45 ± 0.09 at 30-60 s, and 0.46 ± 0.09 at 60-90 s. Gray and white matter CBF values were 61.4 ± 11.0 and 15.6 ± 3.0 mL/min/100 g tissue using sampled blood data. Using IDIF centerlines scaled by the average aRC over each subjects’ injections, gray and white matter CBF values were 61.3 ± 13.5 and 15.5 ± 3.4 mL/min/100 g tissue. Using global average aRC values, the means were unchanged, and intersubject variability was noticeably reduced. This MR-based centerline method with local re-registration to [15O]water PET yields a consistent IDIF over multiple injections in the same subject, thus permitting the absolute quantification of CBF without arterial input function measurements.