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Sample records for 15o brain pet

  1. Evaluation of the ECAT EXACT HR{sup +} 3D PET scanner in {sup 15}O-water brain activation studies

    SciTech Connect

    Moreno-Cantu, J.J.; Thompson, C.J.; Zatorre, R.J.

    1996-12-31

    We evaluated the performance of the ECAT EXACT HR{sup +} 3D whole body PET scanner when employed to measure brain function using {sup 15}O-water-bolus activation protocols in single data acquisition sessions. Using vibrotactile and auditory stimuli as independent activation tasks, we studied the scanner`s performance under different imaging conditions in four healthy volunteers. Cerebral blood flow images were acquired from each volunteer using {sup 15}O-water-bolus injections of activity varying from 5 to 20mCi. Performance characteristics. The scanner`s dead time grew linearly with injected dose from 10% to 25%. Random events varied from 30% to 50% of the detected events. Scattered events were efficiently corrected at all doses. Noise-effective-count curves plateau at about 15mCi. One-session 12-injection bolus PET activation protocol. Using an acquisition protocol that accounts for the scanner`s performance and the practical aspects of imaging volunteers and patients in one session, we assessed the correlation between the statistical significance of activation foci and the dose per injection used The one-session protocol employs 12 bolus injections per subject. We present evidence suggesting that 15-20mCi is the optimal dose per injection to be used routinely in one-time scanning sessions.

  2. Intersubject variability and reproducibility of 15O PET studies.

    PubMed

    Coles, Jonathan P; Fryer, Tim D; Bradley, Peter G; Nortje, Jurgens; Smielewski, Peter; Rice, Kenneth; Clark, John C; Pickard, John D; Menon, David K

    2006-01-01

    Oxygen-15 positron emission tomography (15O PET) can provide important data regarding patients with head injury. We provide reference data on intersubject variability and reproducibility of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolism (CMRO2) and oxygen extraction fraction (OEF) in patients and healthy controls, and explored alternative ways of assessing reproducibility within the context of a single PET study. In addition, we used independent measurements of CBF and CMRO2 to investigate the effect of mathematical correlation on the relationship between flow and metabolism. In patients, intersubject coefficients of variation (CoV) for CBF, CMRO2 and OEF were larger than in controls (32.9%+/-2.2%, 23.2%+/-2.0% and 22.5%+/-3.4% versus 13.5%+/-1.4%, 12.8%+/-1.1% and 7.3%+/-1.2%), while CoV for CBV were lower (15.2%+/-2.1% versus 22.5%+/-2.8%) (P<0.001). The CoV for the test-retest reproducibility of CBF, CBV, CMRO2 and OEF in patients were 2.1%+/-1.5%, 3.8%+/-3.0%, 3.7%+/-3.0% and 4.6%+/-3.5%, respectively. These were much lower than the intersubject CoV figures, and were similar to alternative measures of reproducibility obtained by fractionating data from a single study. The physiological relationship between flow and metabolism was preserved even when mathematically independent measures were used for analysis. These data provide a context for the design and interpretation of interventional PET studies. While ideally each centre should develop its own bank of such data, the figures provided will allow initial generic approximations of sample size for such studies. PMID:15988475

  3. Cortical activation in profoundly deaf patients during cochlear implant stimulation demonstrated by H sub 2 (15)O PET

    SciTech Connect

    Herzog, H.; Lamprecht, A.; Kuehn, A.R.; Roden, W.; Vosteen, K.H.; Feinendegen, L.E. )

    1991-05-01

    Cochlear implants (CIs) are used to provide sensations of sound to profoundly deaf patients. The performance of the CI is assessed mainly by the subjective reports of patients. The aim of this study was to look for objective cortical responses to the stimulation of the CI. Two postlingually and two prelingually deaf patients were investigated by positron emission tomography (PET) using {sup 15}O-labeled water (H{sub 2}{sup 15}O) to determine the regional cerebral blood flow (rCBF). Instead of quantifying rCBF in absolute terms, it was estimated by referring the regional tissue concentration of H{sub 2}{sup 15}O to the mean whole brain concentration. CI stimulation encoded from white noise and sequential words led to an increased rCBF in the primary and secondary (Wernicke) auditory cortex. Relative elevations of up to 33% were observed bilaterally, although they were higher contralateral to the CI. These results were obtained not only in the postlingually deaf patients but also in two patients who had never been able to hear. Thus, it could be demonstrated that PET measurements of cerebral H{sub 2}{sup 15}O distribution yield objective responses of the central auditory system during electrical stimulation by CIs in profoundly deaf patients.

  4. Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man

    NASA Astrophysics Data System (ADS)

    Hori, Yuki; Hirano, Yoshiyuki; Koshino, Kazuhiro; Moriguchi, Tetsuaki; Iguchi, Satoshi; Yamamoto, Akihide; Enmi, Junichiro; Kawashima, Hidekazu; Zeniya, Tsutomu; Morita, Naomi; Nakagawara, Jyoji; Casey, Michael E.; Iida, Hidehiro

    2014-09-01

    Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the

  5. Adequacy of a compartment model for CMRO2 quantitation using 15O-labeled oxygen and PET: a clearance measurement of 15O-radioactivity following intracarotid bolus injection of 15O-labeled oxyhemoglobin on Macaca fascicularis

    PubMed Central

    Iida, Hidehiro; Iguchi, Satoshi; Teramoto, Noboru; Koshino, Kazuhiro; Zeniya, Tsutomu; Yamamoto, Akihide; Kudomi, Nobuyuki; Moriguchi, Tetsuaki; Hori, Yuki; Enmi, Junichiro; Kawashima, Hidekazu; Joni Shah, Nadim; Nakagawara, Jyoji

    2014-01-01

    We aimed at evaluating the adequacy of the commonly employed compartmental model for quantitation of cerebral metabolic rate of oxygen (CMRO2) using 15O-labeled oxygen (15O2) and positron emission tomography (PET). Sequential PET imaging was carried out on monkeys following slow bolus injection of blood samples containing 15O2–oxyhemoglobin (15O2–Hb), 15O-labeled water (H215O), and C15O-labeled hemoglobin (C15O–Hb) into the internal carotid artery (ICA). Clearance slopes were assessed in the middle cerebral artery territory of the injected hemisphere. The time–activity curves were bi-exponential for both 15O2–Hb and H215O. Single exponential fitting to the early (5 to 40 seconds) and late (80 to 240 seconds) periods after the peak was performed and the 15O2–Hb and H215O results were compared. It was found that a significant difference between the clearance rates of the 15O2–Hb and H215O injections is unlikely, which supports the mathematical model that is widely used to describe the kinetics of 15O2–Hb and H215O in cerebral tissues and is the basis of recent approaches to simultaneously assess CMRO2 and cerebral blood flow in a single PET session. However, it should be noted that more data are necessary to unequivocally confirm the result. PMID:25005879

  6. Quantitative agreement between [(15) O]H2 O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

    PubMed

    Heijtel, D F R; Petersen, E T; Mutsaerts, H J M M; Bakker, E; Schober, P; Stevens, M F; van Berckel, B N M; Majoie, C B L M; Booij, J; van Osch, M J P; van Bavel, E T; Boellaard, R; Lammertsma, A A; Nederveen, A J

    2016-04-01

    The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15) O]H2 O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2) : 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2) : 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15) O]H2 O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15) O]H2 O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15) O]H2 O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26876426

  7. A continuous [{sup 15}O]H{sub 2}O production and infusion system for PET imaging

    SciTech Connect

    Sajjad, Munawwar; Liow, Jeih-San

    1999-06-10

    A system for continuous production and infusion of [{sup 15}O]H{sub 2}O has been designed for PET cerebral blood flow studies. The injection system consists of a four-port-two-position valve, two Horizon Nxt infusion pumps, and a sterile 50 ml vial. The variation of the production of [{sup 15}O]H{sub 2}O was <1%. The variation of activity delivered measured by scanner counts during the steady state period was <2%.

  8. Brain PET scan

    MedlinePlus

    ... tests, such as magnetic resonance imaging ( MRI ) and computed tomography ( CT ) scans only reveal the structure of the ... a PET/CT. Alternative Names ... PT, Rijntjes M, Weiller C. Neuroimaging: Functional neuroimaging. In: Daroff RB, Fenichel GM, Jankovic ...

  9. Optimization of methods for quantification of rCBF using high-resolution [15O]H2O PET images

    NASA Astrophysics Data System (ADS)

    Walker, M. D.; Feldmann, M.; Matthews, J. C.; Anton-Rodriguez, J. M.; Wang, S.; Koepp, M. J.; Asselin, M.-C.

    2012-04-01

    This study aimed to derive accurate estimates of regional cerebral blood flow (rCBF) from noisy dynamic [15O]H2O PET images acquired on the high-resolution research tomograph, while retaining as much as possible the high spatial resolution of this brain scanner (2-3 mm) in parametric maps of rCBF. The PET autoradiographic method and generalized linear least-squares (GLLS), with fixed or extended to include spatially variable estimates of the dispersion of the measured input function, were compared to nonlinear least-squares (NLLS) for rCBF estimation. Six healthy volunteers underwent two [15O]H2O PET scans with continuous arterial blood sampling. rCBF estimates were obtained from three image reconstruction methods (one analytic and two iterative, of which one includes a resolution model) to which a range of post-reconstruction filters (3D Gaussian: 2, 4 and 6 mm FWHM) were applied. The optimal injected activity was estimated to be around 11 MBq kg-1 (800 MBq) by extrapolation of patient-specific noise equivalent count rates. Whole-brain rCBF values were found to be relatively insensitive to the method of reconstruction and rCBF quantification. The grey and white matter rCBF for analytic reconstruction and NLLS were 0.44 ± 0.03 and 0.15 ± 0.03 mL min-1 cm-3, respectively, in agreement with literature values. Similar values were obtained from the other methods. For generation of parametric images using GLLS or the autoradiographic method, a filter of ⩾4 mm was required in order to suppress noise in the PET images which otherwise produced large biases in the rCBF estimates.

  10. 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

  11. An apparatus for the preparation of [{sup 15}O]-H{sub 2}O for rapid repetitive PET studies

    SciTech Connect

    Dahl, J. R.; Chaly, T. C.; Matacchieri, R. A.; Yee, A.; Dhawan, V.; Horowitz, S.; Jespersen, K.; Margouleff, D.; Eidelberg, D.

    1999-06-10

    The use of [{sup 15}O]-H{sub 2}O to follow changes in cerebral blood flow using PET has become frequent and widespread, requiring an apparatus easily operated by personnel unfamiliar with the physics and chemistry involved. Oxygen-15 is prepared by the {sup 14}N(d,n){sup 15}O nuclear reaction using a target of UHP nitrogen with 1% UHP hydrogen added, contained in a target chamber similar to that reported for the preparation of [{sup 18}F]-F{sub 2}. Nucleogenic {sup 15}O reacts with hydrogen in the target gas to produce [{sup 15}O]-H{sub 2}O. Some of the N target reacts with hydrogen to produce NH{sub 3}, which must be removed. At the end of bombardment (minimum 6 min.) the target gas is released through a small amount of parenteral water which then flows through approximately 50 mg Dowex 50W-X8 resin (100-200 mesh) to remove the NH{sub 3}. Sufficient 23.4% NaCl solution is added to produce an isotonic solution. The isotonic solution is sterilized by filtration through a 0.22 micron filter into an injection syringe which is sent via pneumatic transport to the PET imaging room. The apparatus, which uses a programmable logic controller and four switches to allow the operator to select standby, refill, collect activity, or deliver dose operations of the production process, provides doses of [{sup 15}O]-H{sub 2}O up to 35 mCi/dose at intervals as frequent as seven minutes with minimal radiation exposure to the operators.

  12. An apparatus for the preparation of [15O]-H2O for rapid repetitive PET studies

    NASA Astrophysics Data System (ADS)

    Dahl, J. R.; Chaly, T. C.; Matacchieri, R. A.; Yee, A.; Dhawan, V.; Horowitz, S.; Jespersen, K.; Margouleff, D.; Eidelberg, D.

    1999-06-01

    The use of [15O]-H2O to follow changes in cerebral blood flow using PET has become frequent and widespread, requiring an apparatus easily operated by personnel unfamiliar with the physics and chemistry involved. Oxygen-15 is prepared by the 14N(d,n)15O nuclear reaction using a target of UHP nitrogen with 1% UHP hydrogen added, contained in a target chamber similar to that reported for the preparation of [18F]-F2. Nucleogenic 15O reacts with hydrogen in the target gas to produce [15O]-H2O. Some of the N target reacts with hydrogen to produce NH3, which must be removed. At the end of bombardment (minimum 6 min.) the target gas is released through a small amount of parenteral water which then flows through approximately 50 mg Dowex 50W-X8 resin (100-200 mesh) to remove the NH3. Sufficient 23.4% NaCl solution is added to produce an isotonic solution. The isotonic solution is sterilized by filtration through a 0.22 micron filter into an injection syringe which is sent via pneumatic transport to the PET imaging room. The apparatus, which uses a programmable logic controller and four switches to allow the operator to select standby, refill, collect activity, or deliver dose operations of the production process, provides doses of [15O]-H2O up to 35 mCi/dose at intervals as frequent as seven minutes with minimal radiation exposure to the operators.

  13. A new approach of weighted integration technique based on accumulated images using dynamic PET and H2(15)O

    SciTech Connect

    Yokoi, T.; Kanno, I.; Iida, H.; Miura, S.; Uemura, K. )

    1991-05-01

    We developed a new technique of weighted integration for the measurement of local cerebral blood flow (LCBF) and the blood-tissue partition coefficient (p) using dynamic positron emission tomography (PET) and H2(15)O. The weighted integration in the new technique is carried out on the equation of the first time integration of the Kety-Schmidt differential equation. Practically, serially accumulated images with sequentially prolonged accumulation times are weighted by two arbitrary functions. The weighting functions do not have to be differentiated because of the exclusion of the differential term in the starting equation. Consequently, the method does not require data at the end of the scan. The technique was applied to H2(15)O dynamic PET performed on four normal subjects, and was verified to provide a better signal-to-noise ratio than the previously developed integrated projection (IP) technique. Computer simulations were carried out to investigate the effects of statistical noise, tissue heterogeneity, and time delay and dispersion in arterial input function. The simulation showed that the new technique provided about a 1.4 times lower statistical error in both LCBF and p at 50 ml 100 g-1 min-1 compared to the IP technique, and it should be noted that the new technique was less sensitive to the shape of the weighting functions. The new technique provides a new strategy with respect to the statistical error for estimation of LCBF and p.

  14. Production of {sup 17}F, {sup 15}O and other radioisotopes for PET using a 3 MV electrostatic tandem accelerator

    SciTech Connect

    Roberts, A. D.; Davidson, R. J.; Nickles, R. J.

    1999-06-10

    Target systems for the production of positron emitting radioisotopes used for medical research with positron emission tomography (PET) are under development for a 3 MV electrostatic tandem accelerator (NEC 9SDH-2). This machine is intended primarily for the continuous production of short lived tracers labeled with {sup 15}O (t{sub 1/2}=122 s) or {sup 17}F (t{sub 1/2}=65 s) for determining regional cerebral blood flow in humans. Simple gas, liquid, and solid target systems are presented for the production of [{sup 15}O]H{sub 2}O (yield at saturation 13 mCi/{mu}A), [{sup 17}F]F{sub 2} (22 mCi/{mu}A), [{sup 17}F] fluoride (aq.) (12 mCi/{mu}A), [{sup 18}F]fluoride (aq.) (21 mCi/{mu}A), [{sup 13}N] in graphite (25 mCi/{mu}A), and [{sup 11}C]CO{sub 2} (2.3 mCi/{mu}A). Current limitations on single window targets for each production are discussed.

  15. Is perivetricular hyperintensity region caused by decreased cerebral blood flow?; assessment by {sup 15}O-PET study

    SciTech Connect

    Kaminaga, T.; Hayashida, K.; Ishida, Y.

    1994-05-01

    The clinical significance of the regional cerebral blood flow (rCBF) and oxygen metabolism has not been established in patients who had periventricular hyperintensity (PVH) by magnetic resonance imaging (MRI). The aim of this study is to correlate the results of rCBF and oxygen metabolism by positron emission tomography (PET) with PVH by MRI. The subjects were 27 patients; 16 patient (group I) (male; 7, female; 9, age; 56.8{plus_minus}18.6) with PVH and age matched 11 patients (group II) (male; 6, female; 5, age; 55.3{plus_minus}13.6) without PVH. {sup 15}O-PET study was carried out by Headtome IV and rCBF, cerebral metabolic rate of oxygen (CMRO{sub 2}), oxygen extraction fraction (OEF) of PVH and cerebellum was calculated. T1- and T2-weighted images were obtained in all patients. Angiography was performed over 11 patients. The mean rCBF of group I in PVH (28.5{plus_minus}7.5 ml/100g/min) was significantly (p<0.01) lower than that of group II (38.6{plus_minus}5.7). The mean rCBF of group I and group II in cerebellum were 49.5{plus_minus}9.9 ml/100g/min and 50.2{plus_minus}8.9 respectively. There was no significant difference on CMRO{sub 2} and OEF between group I and group II. In MRI examination, PVH was detected in all group I patients and multiple high intensities were also detected in 7 patients of group I and 4 patients of group II on T2-weighted images. No significant stenosis (more than 75%) was detected in 11 patients by angiography. These data strongly indicate that PVH might be caused by decreased cerebral blood flow.

  16. Verification of a semi-automated MRI-guided technique for non-invasive determination of the arterial input function in 15O-labeled gaseous PET

    NASA Astrophysics Data System (ADS)

    Iguchi, Satoshi; Hori, Yuki; Moriguchi, Tetsuaki; Morita, Naomi; Yamamoto, Akihide; Koshino, Kazuhiro; Kawashima, Hidekazu; Zeniya, Tsutomu; Enmi, Jun-ichiro; Iida, Hidehiro

    2013-02-01

    A semi-automated MR-guided technique has been evaluated for non-invasive estimation of cerebral metabolic rate of oxygen (CMRO2) using the sequential administration of 15O oxygen (O2) and 15O carbon dioxide (CO2) during a single PET scan. Two mathematical models, which assess the arterial input function (AIF) from time-activity curves (TAC) in the internal carotid artery region, were tested, namely one with a simple correction for the recovery coefficient (RC) and another with corrections for RC and spillover from surrounding tissues. RC was determined from MRA and black-blood image. RC was also determined from C15O blood volume images as a reference. RC agreed between MR-based and C15O-PET based methods, suggesting validity of MR-based methods. Area-under-the-curve (AUC) of the early portion of estimated AIF agreed with that of measured AIF in both models. AUC of the delayed phase of estimated AIF was largely overestimated in the first model, but was sufficiently improved by the spillover correction implemented in the second model.

  17. Perfusion-CT compared to H215O/O15O PET in Patients with Chronic Cervical Carotid Artery Occlusion

    PubMed Central

    Kamath, Amita; Smith, Wade S.; Powers, William J.; Cianfoni, Alessandro; Chien, Jeffrey D.; Videen, Tom; Lawton, Michael T.; Finley, Bruce; Dillon, William P.; Wintermark, Max

    2008-01-01

    Background and Purpose As part of the Carotid Occlusion Surgery Study (COSS), patients with chronic cervical carotid artery occlusive disease are selected for extracranial-intracranial bypass surgery based on the results of 15O2/H215O PET imaging. The purpose of this study was to compare the results of Perfusion-CT (PCT) with those of 15O2/H215O PET in a subset of COSS patients. Materials & Methods Six patients enrolled in COSS underwent a standard-of-care PCT in addition to the 15O2/H215O PET study used for determining study eligibility. PCT and PET studies were coregistered and then processed separately by different radiologists. Relative measurement of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) without arterial sampling were calculated from two PET scans, one for O15O inhalation and one for H215O injection. PCT datasets were processed using different arterial input functions (AIF), on the side of the carotid occlusion (“ischemic” inputs) and on the contralateral side (“nonischemic” inputs). The same sets of symmetric regions of interests (anterior, middle and posterior cerebral artery distribution) were drawn on both hemispheres on matching slices from both imaging modalities (PCT and PET). Relative PCT and PET CBF values (“ischemic” side divided by “nonischemic” side) were compared using linear regression model, in order to determine the most appropriate arterial input function for PCT. As a secondary analysis, PCT values of relative CBF, cerebral blood volume (CBV) and mean transit time (MTT) using the most accurate arterial input function were evaluated for linear regression with respect to relative PET OEF values, which are used for determining study eligibility in COSS. Results The most accurate PCT relative CBF maps with respect to the gold standard PET CBF, were obtained when CBF values for each arterial territory are calculated using a dedicated AIF for each territory (ACA AIF for ACA territory, right MCA AIF for right

  18. 15O PET Measurement of Blood Flow and Oxygen Consumption in Cold-Activated Human Brown Fat

    PubMed Central

    Muzik, Otto; Mangner, Thomas J.; Leonard, William R.; Kumar, Ajay; Janisse, James; Granneman, James G.

    2013-01-01

    Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog 18F-FDG has shown unequivocally the existence of functional BAT in adult humans, suggesting that many humans retain some functional BAT past infancy. The objective of this study was to determine to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and 18F-FDG tracer uptake. Methods Twenty-five healthy adults (15 women and 10 men; mean age ± SD, 30 ± 7 y) underwent triple-oxygen scans (H215O, C15O, and 15O2) as well as measurements of daily energy expenditure (DEE; kcal/d) both at rest and after exposure to mild cold (15.5°C [60°F]) using indirect calorimetry. The subjects were divided into 2 groups (high BAT and low BAT) based on the presence or absence of 18F-FDG tracer uptake (standardized uptake value [SUV] > 2) in cervical–supraclavicular BAT. Blood flow and oxygen extraction fraction (OEF) were calculated from dynamic PET scans at the location of BAT, muscle, and white adipose tissue. Regional blood oxygen saturation was determined by near-infrared spectroscopy. The total energy expenditure during rest and mild cold stress was measured by indirect calorimetry. Tissue-level metabolic rate of oxygen (MRO2) in BAT was determined and used to calculate the contribution of activated BAT to DEE. Results The mass of activated BAT was 59.1 ± 17.5 g (range, 32–85 g) in the high-BAT group (8 women and 1 man; mean age, 29.6 ± 5.5 y) and 2.2 ± 3.6 g (range, 0–9.3 g) in the low-BAT group (9 men and 7 women; mean age, 31.4 ± 10 y). Corresponding maximal SUVs were significantly higher in the high-BAT group than in the low-BAT group (10.7 ± 3.9 vs. 2.1 ± 0.7, P = 0.01). Blood flow values were significantly higher in the high-BAT group than in the low-BAT group for BAT (12.9 ± 4.1 vs. 5.9 ± 2.2 mL/100 g/min, P = 0

  19. Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: a validation study using (15)O-water.

    PubMed

    Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

    2014-01-01

    Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog ((68)Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 (15)O) and 30-min (68)Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 (15)O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of (68)Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the (68)Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 (15)O-based blood flow and (68)Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that (68)Ga-DOTA PET imaging is useful for the quantification of

  20. Assessment of blood flow with 68Ga-DOTA PET in experimental inflammation: a validation study using 15O-water

    PubMed Central

    Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

    2014-01-01

    Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N‘,N‘‘,N‘‘‘-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog (68Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 15O) and 30-min 68Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 15O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of 68Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the 68Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 15O-based blood flow and 68Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that 68Ga-DOTA PET imaging is useful for the quantification of increased

  1. Quantitative PET imaging with the 3T MR-BrainPET

    NASA Astrophysics Data System (ADS)

    Weirich, C.; Scheins, J.; Lohmann, P.; Tellmann, L.; Byars, L.; Michel, C.; Rota Kops, E.; Brenner, D.; Herzog, H.; Shah, N. J.

    2013-02-01

    The new hybrid imaging technology of MR-PET allows for simultaneous acquisition of versatile MRI contrasts and the quantitative metabolic imaging with PET. In order to achieve the quantification of PET images with minimal residual error the application of several corrections is crucial. In this work we present our results on quantification with the 3T MR BrainPET scanner.

  2. Re: Brain blood-flow measurement with bolus intravenous H/sub 2//sup 15/O

    SciTech Connect

    Lambrecht, R.M.; Rescigno, A.

    1984-06-01

    Recently Raichle and colleagues described an implementation of the PET/autoradiographic technique for the measurement of regional cerebral blood flow with intravenously administered oxygen-15-labeled water. They successfully modified the operational equation of the one compartment arising from the Kety-Schmidt method to compensate for the fact that current PET instruments cannot measure the instantaneous tissue count rate. PET images typically require the summing of decay events for the order of 5-180 seconds. Raichle et al. critically outlined several potential sources of error in the adaptation of tissue autoradiography to PET. Although their model has limitations, which they noted, it does offer a convenient and validated method for determining regional cerebral blood flow with a diffusible tracer. We agree with the authors that an appreciation of the validity of assumptions in the kinetic models and their accuracy will lead to more precise quantification of regional cerebral blood flow with positron emission tomography. We are therefore taking exception to the generality of the assertion that the duration of a PET study to determine CBF must be constrained such that the length of data collection must not exceed 1 min for accurate, quantitative results. We suggest that their caveat is specific to the model and the method of approximation of the instantaneous tissue concentration following bolus injection of tracer.

  3. Temporal alignment of tissue and arterial data and selection of integration start times for the H[sub 2] [sup 15]O autoradiographic CBF model in PET

    SciTech Connect

    Muzic, R.F. Jr. . Dept. of Biomedical Engineering); Nelson, A.D.; Miraldi, F. . Div. of Nuclear Medicine)

    1993-09-01

    A technique has been developed and tested that provides an automated method of temporally aligning the PET tissue activity curve with the arterial activity curve for quantification of cerebral blood flow using the H[sub 2] [sup 15]O autoradiographic model. This technique not only determines the relative time delay between the two curves, but also provides the start time of integration. Variability in computing global cerebral blood flow using this technique is shown to be less than that obtained by trained observers manually selecting parameters and at least as good as that obtained by using another automated alignment technique.

  4. Brain PET in the Diagnosis of Alzheimer’s Disease

    PubMed Central

    Marcus, Charles; Mena, Esther; Subramaniam, Rathan M.

    2015-01-01

    Objectives The aim of this article was to review the current role of brain PET in the diagnosis of Alzheimer dementia. The characteristic patterns of glucose metabolism on brain FDG-PET can help in differentiating Alzheimer’s disease from other causes of dementia such as frontotemporal dementia and dementia of Lewy body. Amyloid brain PET may exclude significant amyloid deposition and thus Alzheimer’s disease in appropriate clinical setting. Conclusions FDG-PET and amyloid PET imaging are valuable in the assessment of patients with Alzheimer’s disease. PMID:25199063

  5. 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

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

    PubMed

    Jones, Terry; Rabiner, Eugenii A

    2012-07-01

    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

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

    SciTech Connect

    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

    2015-05-15

    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. 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. 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

  8. Clinical application of PET for the evaluation of brain tumors

    SciTech Connect

    Coleman, R.E.; Hoffman, J.M.; Hanson, M.W.; Sostman, H.D.; Schold, S.C. )

    1991-04-01

    The combination of FDG and PET has demonstrated clinical utility in the evaluation of patients with brain tumors. At the time of diagnosis, FDG PET provides information concerning the degree of malignancy and patient prognosis. After therapy, FDG PET is able to assess persistence of tumor, determine degree of malignancy, monitor progression, differentiate recurrence from necrosis, and assess prognosis. Other studies using PET provide information that may be clinically useful. Determination of tumor blood flow and permeability of the blood-brain barrier may help in the selection of appropriate therapy. Amino acid imaging using 11C-methionine is being evaluated in patients with brain tumors and provides different information than FDG imaging.52 references.

  9. Regional deconvolution method for partial volume correction in brain PET

    NASA Astrophysics Data System (ADS)

    Rusinek, Henry; Tsui, Wai-Hon; de Leon, Mony J.

    2001-05-01

    Correction of PET images for partial volume effects (PVE) is of particular utility in studies of metabolism in brain aging and brain disorders. PVE is commonly corrected using voxel-by- voxel factors obtained from a high resolution brain mask (obtained from the coregistered MR scan), after convolution with the point spread function (PSF) of the imaging system. In a recently proposed regional deconvolution (RD) method, the observed regional activity is expressed as linear combinations of the true metabolic activity. The weights are obtained by integrating the PSF over the geometric extent of the brain regions. We have analyzed the accuracy of RD and two other PVE correction algorithms under a variety of conditions using simulated PET scans. Each of the brain regions was assigned a distribution of metabolic activity, with gray matter/white matter contrast representative of subjects in several age categories. Simulations were performed over a wide range of PET resolutions. The influence of PET/MR misregistration and heterogeneity of brain metabolism were also evaluated. Our results demonstrate the importance of correcting PET metabolic images for PVE. Without such correction, the regional brain activity values are contaminated with 30 - 40% errors. Under most conditions studied, the accuracy of RD and of the three- compartmental method were superior to the accuracy of the two- compartmental method. Our study provides the first demonstration of the feasibility of RD algorithm to provide accurate correction for a large number (n equals 109) of brain compartments. PVE correction methods appear to be promising tools in studies of metabolism in normal brain, brain aging, and brain disorders.

  10. PET radiopharmaceuticals for probing enzymes in the brain

    PubMed Central

    Holland, Jason P; Cumming, Paul; Vasdev, Neil

    2013-01-01

    Biologically important processes in normal brain function and brain disease involve the action of various protein-based receptors, ion channels, transporters and enzymes. The ability to interrogate the location, abundance and activity of these entities in vivo using non-invasive molecular imaging can provide unprecedented information about the spatio-temporal dynamics of brain function. Indeed, positron emission tomography (PET) imaging is transforming our understanding of the central nervous system and brain disease. Great emphasis has historically been placed on developing radioligands for the non-invasive detection of neuroreceptors. In contrast, relatively few enzymes have been amenable to examination by PET imaging procedures based upon trapping or accumulation of enzymatic products, because only a subset of enzymes have sufficient catalytic rate to produce measureable accumulation within the practical time-limit of PET recordings. However, high affinity inhibitors are now serving as tracers for enzymes, particularly for measuring the abundance of enzymes mediating intracellular signal transduction in the brain, which offer a rich diversity of potential targets for drug discovery. The purpose of this review is to summarize well-known radiotracers for brain enzymes, and draw attention to recent developments in PET radiotracers for imaging signal transduction pathways in the brain. The review is organized by target class and focuses on structural chemistry of the best-established radiotracers identified in each class. PMID:23638333

  11. Brain blood flow measured with intravenous H/sub 2/ /sup 15/O. II. Implementation and validation

    SciTech Connect

    Raichle, M.E.; Martin, W.R.W.; Herscovitch, P.; Mintun, M.A.; Markham, J.

    1983-09-01

    The well-known tissue autoradiographic technique for the measurement of regional cerebral blood flow (CBF), originally proposed by Kety and his colleagues has been adapted for the measurement of CBF in human subjects using positron emission tomography (PET) and intravenously administered oxygen-15-labeled water. This report describes the steps necessary for the implementation of this PET/autoradiographic technique. In order to establish the accuracy of the method, we measured CBF with intravenously administered oxygen-15-labeled water and PET in anesthetized adult baboons and compared the results with blood flow measured by a standard tracer technique that uses residue detection of a bolus of oxygen-15-labeled water injected into the internal carotid artery. The correlation between CBF measured with PET and the true CBF for the same cerebral hemisphere was excellent.

  12. FDG and (82)Rb PET/MRI features of brain metastasis of breast cancer.

    PubMed

    Lu, Yang

    2015-06-01

    A 64-year-old woman with stage IV breast cancer underwent an FDG and Rb PET brain studies. The PET brain images were fused with MRI brain T1 post-contrast images. The known enhancing left superoposterior frontal brain metastasis is positive on both FDG Rb PET/MRI images. The Rb PET/MRI showed better target-to-noise ratio, but showed nonspecific uptake in the superior sagittal sinus. PMID:25674864

  13. Study of the production yields of 18F, 11C, 13N and 15O positron emitters from plasma-laser proton sources at ELI-Beamlines for labeling of PET radiopharmaceuticals

    NASA Astrophysics Data System (ADS)

    Amato, Ernesto; Italiano, Antonio; Margarone, Daniele; Pagano, Benedetta; Baldari, Sergio; Korn, Georg

    2016-03-01

    The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of microfluidics labeling approaches. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources such that expected at the ELI-Beamlines facility. 18F, 11C, 13N and 15O production yields were calculated through the TALYS software, by taking into account the broad proton spectra expected. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of 18F-, 11C- and 13N-labeled radiopharmaceuticals exploiting fast and efficient microfluidic labeling systems.

  14. PET evaluation of the dopamine system of the human brain

    SciTech Connect

    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, 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.

  15. Brain blood flow measured with intravenous H/sub 2//sup 15/O. I. Theory and error analysis

    SciTech Connect

    Herscovitch, P.; Markham, J.; Raichle, M.E.

    1983-09-01

    The tissue autoradiographic method for the measurement of regional cerebral blood flow (rCBF) in animals was adapted for use with positron emission tomography (PET). Because of the limited spatial resolution of PET, a region of interest will contain a mix of gray and white matter, inhomogeneous in flow and in tracer partition coefficient (lambda). The resultant error in rCBF, however, is less than 4%. Although the tissue autoradiographic method requires a monotonically increasing input function to ensure a unique solution for flow, the PET adaptation does not, because of an additional integration in the operational equation. Simulation showed that the model is accurate in the presence of ischemia or hyperemia of the gray matter. Inaccuracy in timing of the arterial input function will result in large errors in rCBF measurement. Propagation of errors in measurement of tissue activity is largely independent of flow, reflecting the nearly linear flow compared with activity relationship.

  16. Brain blood flow measured with intravenous H/sub 2//sup 15/O. I. Theory and error analysis

    SciTech Connect

    Herscovitch, P.; Markham, J.; Raichle, M.E.

    1983-09-01

    The tissue autoradiographic method for the measurement of regional cerebral blood flow (rCBF) in animals was adapted for use with positron emission tomography (PET). Because of the limited spatial resolution of PET, a region of interest will contain a mix of gray and white matter, inhomogeneous in flow and in tracer partition coefficient (lambda). The resultant error in rCBF, however, is less than 4%. Although the tissue autoradiographic method requires a monotonically increasing input function to ensure a unique solution for flow, the PET adaptation does not, because of an additional integration in the operational equation. Simulation showed that the model is accurate in the presence of ischemia or hyperemia fo the gray matter. Inaccuracy in timing of the arterial input function will result in large errors in rCBF measurement. Propagation of errors in measurement of tissue activity is largely independent of flow, reflecting the nearly linear flow compared with activity relationship.

  17. Stereotactic PET atlas of the human brain: Aid for visual interpretation of functional brain images

    SciTech Connect

    Minoshima, S.; Koeppe, R.A.; Frey, A.; Ishihara, M.; Kuhl, D.E.

    1994-06-01

    In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. The PET atlas was constructed from a high-resolution [{sup 18}F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-ld woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer`s disease, and areas of functional alteration were localized visually by referring to the PET atlas. Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer`s disease facilitated both indirect and direct localization of the cerebral structures. Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations. 41 refs., 3 figs.

  18. Compact and mobile high resolution PET brain imager

    DOEpatents

    Majewski, Stanislaw; Proffitt, James

    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.

  19. Hybrid PET/MR Imaging and Brain Connectivity

    PubMed Central

    Aiello, Marco; Cavaliere, Carlo; Salvatore, Marco

    2016-01-01

    In recent years, brain connectivity is gaining ever-increasing interest from the interdisciplinary research community. The study of brain connectivity is characterized by a multifaceted approach providing both structural and functional evidence of the relationship between cerebral regions at different scales. Although magnetic resonance (MR) is the most established imaging modality for investigating connectivity in vivo, the recent advent of hybrid positron emission tomography (PET)/MR scanners paved the way for more comprehensive investigation of brain organization and physiology. Due to the high sensitivity and biochemical specificity of radiotracers, combining MR with PET imaging may enrich our ability to investigate connectivity by introducing the concept of metabolic connectivity and cometomics and promoting new insights on the physiological and molecular bases underlying high-level neural organization. This review aims to describe and summarize the main methods of analysis of brain connectivity employed in MR imaging and nuclear medicine. Moreover, it will discuss practical aspects and state-of-the-art techniques for exploiting hybrid PET/MR imaging to investigate the relationship of physiological processes and brain connectivity. PMID:26973446

  20. Hybrid PET/MR Imaging and Brain Connectivity.

    PubMed

    Aiello, Marco; Cavaliere, Carlo; Salvatore, Marco

    2016-01-01

    In recent years, brain connectivity is gaining ever-increasing interest from the interdisciplinary research community. The study of brain connectivity is characterized by a multifaceted approach providing both structural and functional evidence of the relationship between cerebral regions at different scales. Although magnetic resonance (MR) is the most established imaging modality for investigating connectivity in vivo, the recent advent of hybrid positron emission tomography (PET)/MR scanners paved the way for more comprehensive investigation of brain organization and physiology. Due to the high sensitivity and biochemical specificity of radiotracers, combining MR with PET imaging may enrich our ability to investigate connectivity by introducing the concept of metabolic connectivity and cometomics and promoting new insights on the physiological and molecular bases underlying high-level neural organization. This review aims to describe and summarize the main methods of analysis of brain connectivity employed in MR imaging and nuclear medicine. Moreover, it will discuss practical aspects and state-of-the-art techniques for exploiting hybrid PET/MR imaging to investigate the relationship of physiological processes and brain connectivity. PMID:26973446

  1. Alterations in CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H[subscript 2][superscript 15]O PET Study

    ERIC Educational Resources Information Center

    Ali, S. Omar; Thomassen, Michael; Schulz, Geralyn M.; Hosey, Lara A.; Varga, Mary; Ludlow, Christy L.; Braun, Allen R.

    2006-01-01

    Speech-related changes in regional cerebral blood flow (rCBF) were measured using H[subscript 2][superscript 15]O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest…

  2. Regional cerebral blood flow imaging: A quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET

    SciTech Connect

    Gemmell, H.G.; Evans, N.T.; Besson, J.A.; Roeda, D.; Davidson, J.; Dodd, M.G.; Sharp, P.F.; Smith, F.W.; Crawford, J.R.; Newton, R.H. )

    1990-10-01

    The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime ({sup 99m}Tc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

  3. 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

  4. Simplified, noninvasive PET measurement of blood-brain barrier permeability

    SciTech Connect

    Iannotti, F.; Fieschi, C.; Alfano, B.; Picozzi, P.; Mansi, L.; Pozzilli, C.; Punzo, A.; Del Vecchio, G.; Lenzi, G.L.; Salvatore, M.

    1987-05-01

    Blood-brain barrier (BBB) permeability to (/sup 68/Ga)EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the (/sup 68/Ga)EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes.

  5. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

    PubMed

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson's disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  6. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study

    PubMed Central

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  7. Measuring dopamine release in the human brain with PET

    SciTech Connect

    Volkow, N.D. |; Fowler, J.S.; Logan, J.; Wang, G.J.

    1995-12-01

    The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.

  8. PET imaging of ischemia-induced impairment of mitochondrial complex I function in monkey brain

    PubMed Central

    Tsukada, Hideo; Ohba, Hiroyuki; Nishiyama, Shingo; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Harada, Norihiro

    2014-01-01

    To assess the capability of 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF), a novel positron emission tomography (PET) probe for mitochondrial complex I (MC-I) activity, as a specific marker of ischemia-induced neuronal death without being disturbed by inflammation, translational research was conducted using an animal PET in ischemic brains of Cynomolgus monkeys (Macaca fascicularis). Focal ischemia was induced by the right middle cerebral artery occlusion for 3 hours, then PET scans were conducted at Day-7 with 15O-gases for regional cerebral blood flow (rCBF) and regional cerebral metabolism of oxygen (rCMRO2), and 18F-BCPP-EF for MC-I with arterial blood sampling. On Day-8, the additional PET scans conducted with 11C-flumazenil (11C-FMZ) for central-type benzodiazepine receptors, 11C-PBR28 for translocator protein, and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) for regional cerebral metabolic rate of glucose (rCMRglc). The total distribution volume (VT) values of 18F-BCPP-EF showed the significant reduction in MC-I activity in the damaged area at Day-7. When correlated with rCBF and rCMRO2, the VT values of 18F-BCPP-EF provided better correlation with rCMRO2 than with rCBF. In the inflammatory regions (region of interest, ROIPBR) of the ischemic hemisphere detected with 11C-PBR28, higher 18F-FDG uptake and lower VT of 18F-BCPP-EF, 11C-FMZ, and rCMRO2 than those in normal contralateral hemisphere were observed. These results strongly suggested that 18F-BCPP-EF could discriminate the neuronal damaged areas with neuroinflammation, where 18F-FDG could not owing to its high uptake into the activated microglia. PMID:24447952

  9. Clinical applications of choline PET/CT in brain tumors.

    PubMed

    Giovannini, Elisabetta; Lazzeri, Patrizia; Milano, Amalia; Gaeta, Maria Chiara; Ciarmiello, Andrea

    2015-01-01

    Malignant gliomas and metastatic tumors are the most common forms of brain tumors. From a clinical perspective, neuroimaging plays a significant role, in diagnosis, treatment planning, and follow-up. To date MRI is considered the current clinical gold standard for imaging, however, despite providing superior structural detail it features poor specificity in identifying viable tumors in brain treated with surgery, radiation, or chemotherapy. In the last years functional neuroimaging has become largely widespread thanks to the use of molecular tracers employed in cellular metabolism which has significantly improved the management of patients with brain tumors, especially in the post-treatment phase. Despite the considerable progress of molecular imaging in oncology its use in the diagnosis of brain tumors is still limited by a few wellknown technical problems. Because 18F-FDG, the most common radiotracer used in oncology, is avidly accumulated by normal cortex, the low tumor/background signal ratio makes it difficult to distinguish the tumor from normal surrounding tissues. By contrast, radiotracers with higher specificity for the tumor are labeled with a short half-life isotopes which restricts their use to those centers equipped with a cyclotron and radiopharmacy facility. 11C-choline has been reported as a suitable tracer for neuroimaging application. The recent availability of choline labeled with a long half-life radioisotope as 18F increases the possibility of studying this tracer's potential role in the staging of brain tumors. The present review focuses on the possible clinical applications of PET/CT with choline tracers in malignant brain tumors and brain metastases, with a special focus on malignant gliomas. PMID:25225894

  10. Brain shaving: adaptive detection for brain PET data

    NASA Astrophysics Data System (ADS)

    Grecchi, Elisabetta; Doyle, Orla M.; Bertoldo, Alessandra; Pavese, Nicola; Turkheimer, Federico E.

    2014-05-01

    The intricacy of brain biology is such that the variation of imaging end-points in health and disease exhibits an unpredictable range of spatial distributions from the extremely localized to the very diffuse. This represents a challenge for the two standard approaches to analysis, the mass univariate and the multivariate that exhibit either strong specificity but not as good sensitivity (the former) or poor specificity and comparatively better sensitivity (the latter). In this work, we develop an analytical methodology for positron emission tomography that operates an extraction (‘shaving’) of coherent patterns of signal variation while maintaining control of the type I error. The methodology operates two rotations on the image data, one local using the wavelet transform and one global using the singular value decomposition. The control of specificity is obtained by using the gap statistic that selects, within each eigenvector, a subset of significantly coherent elements. Face-validity of the algorithm is demonstrated using a paradigmatic data-set with two radiotracers, [11C]-raclopride and [11C]-(R)-PK11195, measured on the same Huntington's disease patients, a disorder with a genetic based diagnosis. The algorithm is able to detect the two well-known separate but connected processes of dopamine neuronal loss (localized in the basal ganglia) and neuroinflammation (diffusive around the whole brain). These processes are at the two extremes of the distributional envelope, one being very sparse and the latter being perfectly Gaussian and they are not adequately detected by the univariate and the multivariate approaches.

  11. PET-imaging of brain plasticity after cochlear implantation.

    PubMed

    Strelnikov, K; Marx, M; Lagleyre, S; Fraysse, B; Deguine, O; Barone, P

    2015-04-01

    In this article, we review the PET neuroimaging literature, which indicates peculiarities of brain networks involved in speech restoration after cochlear implantation. We consider data on implanted patients during stimulation as well as during resting state, which indicates basic long-term reorganisation of brain functional architecture. On the basis of our analysis of neuroimaging literature and considering our own studies, we indicate that auditory recovery in deaf patients after cochlear implantation partly relies on visual cues. The brain develops mechanisms of audio-visual integration as a strategy to achieve high levels of speech recognition. It turns out that this neuroimaging evidence is in line with behavioural findings of better audiovisual integration in these patients. Thus, strong visually and audio-visually based rehabilitation during the first months after cochlear implantation would significantly improve and fasten the functional recovery of speech intelligibility and other auditory functions in these patients. We provide perspectives for further neuroimaging studies in cochlear implanted patients, which would help understand brain organisation to restore auditory cognitive processing in the implanted patients and would potentially suggest novel approaches for their rehabilitation. This article is part of a Special Issue entitled . PMID:25448166

  12. Optimization of PET instrumentation for brain activation studies

    SciTech Connect

    Dahlbom, M.; Cherry, S.R.; Hoffman, E.J. . Dept. of Radiological Science); Eriksson, L. . Dept. of Clinical Neurophysiology); Wienhard, K. )

    1993-08-01

    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 removable 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.

  13. Human brain development in infants with PET and FDG

    SciTech Connect

    Phelps, M.E.; Chugani, H.T.

    1985-05-01

    The authors used studies of local cerebral metabolic rate for glucose (LCMRGlc) to examine development of cerebral organization in 5 days to 1 year old children. A group (n=8) of infants with diverse pediatric disorders allowed investigation of developmental changes in LCMRGlc, while also providing relevant clinical management information. Patients consisted of questionable and definite neonatal seizures, cerebral embolism from cardiac sources, and otherwise normal infants with facial nevi with consideration of Sturge-Weber. Gradual increase in cortical LCMRGlc coincides with suppression of intrinsic subcortical reflexes present in all newborns. Two retarded children (2 years old) showed LCMRGlc developmental patterns of a few days old, which corresponded to their functional and mental status. These studies illustrate great potential of PET to study normal and altered states of human brain development.

  14. 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.

  15. Simultaneous fMRI-PET of the Opioidergic Pain System in Human Brain

    PubMed Central

    Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M.; Dougherty, Darin D.; Knudsen, Gitte M.; Wang, Danny JJ.; Chonde, Daniel B; Rosen, Bruce R.; Gollub, Randy L.; Kong, Jian

    2015-01-01

    MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [11C]Diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo. PMID:25107855

  16. PET Parametric Response Mapping for Clinical Monitoring and Treatment Response Evaluation in Brain Tumors.

    PubMed

    Ellingson, Benjamin M; Chen, Wei; Harris, Robert J; Pope, Whitney B; Lai, Albert; Nghiemphu, Phioanh L; Czernin, Johannes; Phelps, Michael E; Cloughesy, Timothy F

    2013-04-01

    PET parametric response maps (PRMs) are a provocative new molecular imaging technique for quantifying brain tumor response to therapy in individual patients. By aligning sequential PET scans over time using anatomic MR imaging information, the voxel-wise change in radiotracer uptake can be quantified and visualized. PET PRMs can be performed before and after a particular therapy to test whether the tumor is responding favorably, or performed relative to a distant time point to monitor changes through the course of a treatment. This article focuses on many of the technical details involved in generating, visualizing, and quantifying PET PRMs, and practical applications and example case studies. PMID:27157948

  17. 18F-NaF PET/CT Imaging of Brain Metastases.

    PubMed

    Salgarello, Matteo; Lunardi, Gianluigi; Inno, Alessandro; Pasetto, Stefano; Severi, Fabrizia; Gorgoni, Giancarlo; Gori, Stefania

    2016-07-01

    F-NaF is a radiopharmaceutical widely used in PET imaging to detect bone metastases. Several cases of F-NaF uptake from brain metastases have been described, but a specific protocol for the evaluation of brain metastases with F-NaF has not been developed yet. Here we report images of F-NaF PET/CT, standard CT, and MRI of a brain metastasis in a patient with non-small lung cancer. Through a dynamic acquisition procedure, we have identified the first minutes after injection as the preferable time point of imaging acquisition for the study of brain metastases with F-NaF. PMID:27163462

  18. 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.

  19. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    SciTech Connect

    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.

    2014-06-14

    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 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. 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.

  20. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    DOE PAGESBeta

    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.; et al

    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

  1. 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

  2. Effect of Cyclosporin A on the Uptake of D3-Selective PET Radiotracers in Rat Brain

    PubMed Central

    Tu, Zhude; Li, Shihong; Xu, Jinbin; Chu, Wenhua; Jones, Lynne A.; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    Introduction Four benzamide analogs having a high affinity and selectivity for D3 versus D2 receptors were radiolabeled with 11C or 18F for in vivo evaluation. Methods Precursors were synthesized and the four D3 selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. MicroPET imaging was carried out for [11C]6 in a control and a cyclosporin A pre-treated rat. Results All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-i.v. injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. Conclusions These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other ABC transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters. PMID:21718948

  3. Mapping 15O production rate for proton therapy verification

    PubMed Central

    Grogg, Kira; Alpert, Nathaniel M.; Zhu, Xuping; Min, Chul Hee; Testa, Mauro; Winey, Brian; Normandin, Marc D.; Shih, Helen A.; Paganetti, Harald; Bortfeld, Thomas; El Fakhri, Georges

    2015-01-01

    Purpose This is a proof-of-principle study for the evaluation of 15O production as an imaging target, through the use of positron emission tomography (PET), to improve verification of proton treatment plans and study the effects of perfusion. Methods and Materials Dynamic PET measurements of irradiation-produced isotopes were taken for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged in both live and dead conditions. A differential equation was fitted to the phantom and the in vivo data, yielding estimates of the 15O production and clearance rates, which was compared for live versus dead for the rabbit, and to Monte Carlo (MC) predictions. Results PET clearance rates agreed with the decay constants of the dominant radionuclide species in three different phantom materials. In two oxygen-rich materials, the ratio of 15O production rates agreed with the MC prediction. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using the 15O decay constant, while the live thigh activity decayed faster. Most importantly, the 15O production rates agreed within 2% (p> 0.5) between conditions. Conclusion We developed a new method for quantitative measurement of 15O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of 15O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, 15O clearance rates may be useful in monitoring permeability changes due to therapy. PMID:25817530

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

    SciTech Connect

    Grogg, Kira; Alpert, Nathaniel M.; Zhu, Xuping; Min, Chul Hee; Testa, Mauro; Winey, Brian; Normandin, Marc D.; Shih, Helen A.; Paganetti, Harald; Bortfeld, Thomas; El Fakhri, Georges

    2015-06-01

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

  5. PET Radiotracers: crossing the blood-brain barrier and surviving metabolism

    PubMed Central

    Pike, Victor W.

    2009-01-01

    Radiotracers for imaging protein targets in living human brain with positron emission tomography (PET) are increasingly useful in clinical research and in drug development. Such radiotracers must fulfill many criteria, among which an ability to enter brain adequately and reversibly without contamination by troublesome radiometabolites is desirable for accurate measurement of the density of a target protein (e.g., neuroreceptor, transporter, enzyme or plaque). Candidate radiotracers may fail as a result of poor passive brain entry, rejection from brain by efflux transporters or undesirable metabolism. These issues are reviewed. Emerging PET radiotracers for measuring efflux transporter function, and new strategies for ameliorating radiotracer metabolism are discussed. A growing understanding of the molecular features affecting the brain penetration, metabolism and efflux transporter sensitivity of prospective radiotracers should ultimately lead to their more rational and efficient design, and also to their greater efficacy. PMID:19616318

  6. MRI-guided brain PET image filtering and partial volume correction.

    PubMed

    Yan, Jianhua; Lim, Jason Chu-Shern; 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 (18)F-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. PMID:25575248

  7. 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.

  8. Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.

    PubMed

    Liu, Ping; Hamill, Terence G; Chioda, Marc; Chobanian, Harry; Fung, Selena; Guo, Yan; Chang, Linda; Bakshi, Raman; Hong, Qingmei; Dellureficio, James; Lin, Linus S; Abbadie, Catherine; Alexander, Jessica; Jin, Hong; Mandala, Suzanne; Shiao, Lin-Lin; Li, Wenping; Sanabria, Sandra; Williams, David; Zeng, Zhizhen; Hajdu, Richard; Jochnowitz, Nina; Rosenbach, Mark; Karanam, Bindhu; Madeira, Maria; Salituro, Gino; Powell, Joyce; Xu, Ling; Terebetski, Jenna L; Leone, Joseph F; Miller, Patricia; Cook, Jacquelynn; Holahan, Marie; Joshi, Aniket; O'Malley, Stacey; Purcell, Mona; Posavec, Diane; Chen, Tsing-Bau; Riffel, Kerry; Williams, Mangay; Hargreaves, Richard; Sullivan, Kathleen A; Nargund, Ravi P; DeVita, Robert J

    2013-06-13

    We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain. PMID:24900701

  9. PET imaging of MRP1 function in the living brain: method development and future perspectives.

    PubMed

    Okamura, T; Kikuchi, T; Irie, T

    2010-01-01

    Multidrug resistance-associated protein 1 (MRP1) functions as a primary active transporter utilizing energy from ATP hydrolysis. In the central nervous system (CNS), MRP1 plays an important role in limiting the permeation of xenobiotic and endogenous substrates across the blood-brain and blood-cerebrospinal fluid barriers, and across brain parenchymal cells. While MRP1 contributes to minimizing the neurotoxic effects of drugs, it may also restrict the distribution of drugs for the treatment of CNS diseases. Moreover, neurodegenerative disease may be associated with abnormal expression of efflux transporters in the brain. Noninvasive measurement of MRP1 function will therefore be useful for directly evaluating the effect of modulators on enhancing the penetration of drugs into the brain and for examining the pathophysiological role of MRP1 in the brain. Positron emission tomography (PET) is a powerful molecular imaging technique. While several PET probes have been proposed for imaging function of the efflux transporter P-glycoprotein, few reports discuss the probes for imaging MRP1 function in the brain. Ideally, brain radioactivity should consist of a single radioactive compound that is selectively transported by the efflux transporter of interest, without other efflux routes. However, most PET probes for MRP1 or P-glycoprotein are eliminated by both a transporter and simple diffusion, resulting in inaccurate measurement of pump function. This review addresses a new strategy to avoid this problem, and suggests the design of a PET probe based on this strategy, particularly for MRP1 imaging. Several published reports on imaging MRP1 function with PET are also discussed. PMID:20645911

  10. 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. PMID:26528727

  11. 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.

  12. PET Imaging of Tau Deposition in the Aging Human Brain.

    PubMed

    Schöll, Michael; Lockhart, Samuel N; 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

    2016-03-01

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-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

  13. 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)

  14. 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%.

  15. Technical Considerations in Brain Amyloid PET Imaging with 18F-Florbetapir.

    PubMed

    Trembath, LisaAnn; Newell, Maureen; Devous, Michael D

    2015-09-01

    Technical factors play a critical role in the production of best-quality amyloid PET images for interpretation. This article provides specific instructions and general technical information about PET brain scanning of β-amyloid neuritic plaques. The focus of tracer-specific information will be on (18)F-florbetapir (indications, contraindications, dosing, administration, uptake time, scanning time, acquisition, processing, biodistribution, radiation dose, adverse events, and display). General scanning information relevant to all amyloid-imaging agents will be also be presented (e.g., mechanism of uptake, safe handling, positioning, prevention of patient motion, processing, and artifacts). PMID:26271806

  16. 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

  17. Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET-MR: phantom and non-human primate studies

    PubMed Central

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

    2014-01-01

    Brain PET scanning plays an important role in the diagnosis, prognostication and monitoring of many brain diseases. Motion artifacts from head motion are one of the major hurdles in brain PET. In this work, we propose to use wireless MR active markers to track head motion in real time during a simultaneous PET-MR brain scan and incorporate the motion measured by the markers in the listmode PET reconstruction. Several wireless MR active markers and a dedicated fast MR tracking pulse sequence module were built. Data were acquired on an ACR Flangeless PET phantom with multiple spheres and a non-human primate with and without motion. Motions of the phantom and monkey’s head were measured with the wireless markers using a dedicated MR tracking sequence module. The motion PET data were reconstructed using list-mode reconstruction with and without motion correction. Static reference was used as gold standard for quantitative analysis. The motion artifacts, which were prominent on the images without motion correction, were eliminated by the wireless marker based motion correction in both the phantom and monkey experiments. Quantitative analysis was performed on the phantom motion data from 24 independent noise realizations. The reduction of bias of sphere-to-background PET contrast by active marker based motion correction ranges from 26% to 64% and 17% to 25% for hot (i.e., radioactive) and cold (i.e., non-radioactive) spheres, respectively. The motion correction improved the channelized Hotelling observer signal-to-noise ratio of the spheres by 1.2 to 6.9 depending on their locations and sizes. The proposed wireless MR active marker based motion correction technique removes the motion artifacts in the reconstructed PET images and yields accurate quantitative values. PMID:24418501

  18. Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET-MR: phantom and non-human primate studies.

    PubMed

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

    2014-05-01

    Brain PET scanning plays an important role in the diagnosis, prognostication and monitoring of many brain diseases. Motion artifacts from head motion are one of the major hurdles in brain PET. In this work, we propose to use wireless MR active markers to track head motion in real time during a simultaneous PET-MR brain scan and incorporate the motion measured by the markers in the listmode PET reconstruction. Several wireless MR active markers and a dedicated fast MR tracking pulse sequence module were built. Data were acquired on an ACR Flangeless PET phantom with multiple spheres and a non-human primate with and without motion. Motions of the phantom and monkey's head were measured with the wireless markers using a dedicated MR tracking sequence module. The motion PET data were reconstructed using list-mode reconstruction with and without motion correction. Static reference was used as gold standard for quantitative analysis. The motion artifacts, which were prominent on the images without motion correction, were eliminated by the wireless marker based motion correction in both the phantom and monkey experiments. Quantitative analysis was performed on the phantom motion data from 24 independent noise realizations. The reduction of bias of sphere-to-background PET contrast by active marker based motion correction ranges from 26% to 64% and 17% to 25% for hot (i.e., radioactive) and cold (i.e., non-radioactive) spheres, respectively. The motion correction improved the channelized Hotelling observer signal-to-noise ratio of the spheres by 1.2 to 6.9 depending on their locations and sizes. The proposed wireless MR active marker based motion correction technique removes the motion artifacts in the reconstructed PET images and yields accurate quantitative values. PMID:24418501

  19. No difference in brain activation during cognitive performance between ecstasy (3,4-methylenedioxymethamphetamine) users and control subjects: a [H2(15)O]-positron emission tomography study.

    PubMed

    Gamma, A; Buck, A; Berthold, T; Vollenweider, F X

    2001-02-01

    The long-term use of the serotonin-releaser and uptake-inhibitor 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naive controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [H2(15)O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naive controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use. PMID:11199950

  20. Integrated modeling of PET and DTI information based on conformal brain mapping

    NASA Astrophysics Data System (ADS)

    Zou, Guangyu; Xi, Yongjian; Heckenburg, Greg; Duan, Ye; Hua, Jing; Gu, Xiangfeng

    2006-03-01

    Recent advances in imaging technologies, such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Diffusion Tensor Imaging (DTI) have accelerated brain research in many aspects. In order to better understand the synergy of the many processes involved in normal brain function, integrated modeling and analysis of MRI, PET, and DTI is highly desirable. Unfortunately, the current state-of-art computational tools fall short in offering a comprehensive computational framework that is accurate and mathematically rigorous. In this paper we present a framework which is based on conformal parameterization of a brain from high-resolution structural MRI data to a canonical spherical domain. This model allows natural integration of information from co-registered PET as well as DTI data and lays the foundation for a quantitative analysis of the relationship between diverse data sets. Consequently, the system can be designed to provide a software environment able to facilitate statistical detection of abnormal functional brain patterns in patients with a large number of neurological disorders.

  1. 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

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

    SciTech Connect

    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 uptake 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.

  3. 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

  4. FDG-PET imaging in mild traumatic brain injury: a critical review.

    PubMed

    Byrnes, Kimberly R; Wilson, Colin M; Brabazon, Fiona; von Leden, Ramona; Jurgens, Jennifer S; Oakes, Terrence R; Selwyn, Reed G

    2014-01-01

    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 [(18)F]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

  5. Development and use of a kinetic FDG-PET dataset simulated from the MNI standard brain

    NASA Astrophysics Data System (ADS)

    Schottlander, David; Guimond, Alexandre; Pan, Xiao-Bo; Brady, Michael; Declerck, Jérôme; Collins, Louis; Evans, Alan C.; Reilhac, Anthonin

    2006-03-01

    Simulated data is an important tool for evaluation of reconstruction and image processing algorithms in the frequent absence of ground truth, in-vivo data from living subjects. This is especially true in the case of dynamic PET studies, in which counting statistics of the volume can vary widely over the time-course of the acquisition. Realistic simulated data-sets which model anatomy and physiology, and make explicit the spatial and temporal image acquisition characteristics, facilitate experimentation with a wide range of the conditions anticipated in practice, and which can severely challenge algorithm performance and reliability. As a first example, we have developed a realistic dynamic FDG-PET data-set using the PET-SORTEO Monte Carlo simulation code and the MNI digital brain phantom. The phantom is a three-dimensional data-set that defines the spatial distribution of different tissues. Time activity curves were calculated using an impulse response function specified by generally accepted rate constants, convolved with an input function obtained by blood sampling, and assigned to grey and white matter tissue regions. We created a dynamic PET study using PET-SORTEO configured to simulate an ECAT Exact HR+. The resulting sinograms were reconstructed with all corrections, using variations of FBP and OSEM. Having constructed the dynamic PET data-sets, we used them to evaluate the performance of intensity-based registration as part of a tool for quantifying hyper/hypo perfusion with particular application to analysis of brain dementia scans, and a study of the stability of kinetic parameter estimation.

  6. A Factor-Image Framework to Quantification of Brain Receptor Dynamic PET Studies

    PubMed Central

    Wang, Z. Jane; Szabo, Zsolt; Lei, Peng; Varga, József; Liu, K. J. Ray

    2007-01-01

    The positron emission tomography (PET) imaging technique enables the measurement of receptor distribution or neurotransmitter release in the living brain and the changes of the distribution with time and thus allows quantification of binding sites as well as the affinity of a radioligand. However, quantification of receptor binding studies obtained with PET is complicated by tissue heterogeneity in the sampling image elements (i.e., voxels, pixels). This effect is caused by a limited spatial resolution of the PET scanner. Spatial heterogeneity is often essential in understanding the underlying receptor binding process. Tracer kinetic modeling also often requires an intrusive collection of arterial blood samples. In this paper, we propose a likelihood-based framework in the voxel domain for quantitative imaging with or without the blood sampling of the input function. Radioligand kinetic parameters are estimated together with the input function. The parameters are initialized by a subspace-based algorithm and further refined by an iterative likelihood-based estimation procedure. The performance of the proposed scheme is examined by simulations. The results show that the proposed scheme provides reliable estimation of factor time-activity curves (TACs) and the underlying parametric images. A good match is noted between the result of the proposed approach and that of the Logan plot. Real brain PET data are also examined, and good performance is observed in determining the TACs and the underlying factor images. PMID:18769527

  7. 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. PMID:27405041

  8. 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.

  9. Investigation of partial volume correction methods for brain FDG PET studies

    SciTech Connect

    Yang, J.; Huang, S.C.; Mega, M.; Toga, A.W.; Small, G.W.; Phelps, M.E.; Lin, K.P.

    1996-12-01

    The use of positron emission tomography (PET) in quantitative fluorodeoxyglucose (FDG) studies of aging and dementia has been limited by partial volume effects. A general method for correction of partial volume effects (PVE) in PET involves the following common procedures; segmentation of MRI brain images into gray matter (GM), white matter (WM), cerebral spinal fluid (CSF), and muscle (MS) components; MRI PET registration; and generation of simulated PET images. Afterward, two different approaches can be taken. The first approach derives first a pixel-by-pixel correction map as the ratio of the measured image to the simulated image [with realistic full-width at half-maximum (FWHM)]. The correction map was applied to the MRI segmentation image. Regions of interest (ROI`s) can then be applied to give results free of partial volume effects. The second approach uses the ROI values of the simulated ``pure`` image (with negligible FWHM) and those of the simulated and the measured PET images to correct for the PVE effect. By varying the ratio of radiotracer concentrations for different tissue components, the in-plane FWHM`s of a three-dimensional point spread function, and the ROI size, the authors evaluated the performance of these two approaches in terms of their accuracy and sensitivity to different simulation configurations. The results showed that both approaches are more robust than the approach developed by Muller-Gartner et al., and the second approach is more accurate and more robust than the first. In conclusion, the authors recommend that the second approach should be used on FDG PET images to correct for partial volume effects and to determine whether an apparent change in GM radiotracer concentration is truly due to metabolic changes.

  10. PET studies in epilepsy

    PubMed Central

    Sarikaya, Ismet

    2015-01-01

    . 15O-H2O PET was reported to have a similar sensitivity to FDG-PET in detecting epileptic foci. PMID:26550535

  11. Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients

    PubMed Central

    Van der Aa, Nathalie; Goffin, Karolien; Koole, Michel; Porke, Kathleen; Van De Velde, Marc; Rooms, Liesbeth; Van Paesschen, Wim; Van Esch, Hilde; Van Laere, Koen; Kooy, R. Frank

    2015-01-01

    Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS), a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET) and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome. PMID:26222316

  12. Positron emission tomographic measurement of cerebral blood flow and permeability-surface area product of water using (/sup 15/O)water and (/sup 11/C)butanol

    SciTech Connect

    Herscovitch, P.; Raichle, M.E.; Kilbourn, M.R.; Welch, M.J.

    1987-10-01

    We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H/sub 2/(/sup 15/)O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H/sub 2/(/sup 15/)O, may lead to an underestimation of CBF. We therefore validated the use of (/sup 11/C)butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H/sub 2/(/sup 15/)O, and thereby were able to calculate the extraction Ew and permeability-surface area product PSw of H/sub 2/(/sup 15/)O. Measurements of the permeability of rhesus monkey brain to (/sup 11/C)butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and (/sup 11/C)butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H/sub 2/(/sup 15/)O and (/sup 11/C)butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with (/sup 11/C)butanol (53.1 ml/min-100 g) than with H/sub 2/(/sup 15/)O (44.4 ml/min-100 g). Average global Ew was 0.84 and global PSw was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PSw and CBF, while Ew was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain-blood partition coefficient for (/sup 11/C)butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PSw.

  13. Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

    SciTech Connect

    Redies, C.; Hoffer, L.J.; Beil, C.; Marliss, E.B.; Evans, A.C.; Lariviere, F.; Marrett, S.; Meyer, E.; Diksic, M.; Gjedde, A.

    1989-06-01

    In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged.

  14. Using kinetic parameter analysis of dynamic FDOPA-PET for brain tissue classification

    NASA Astrophysics Data System (ADS)

    Lin, Hong-Dun; Lin, Kang-Ping; Chung, Being-Tau; Yu, Chin-Lung; Wang, Rong-Fa; Wu, Liang-Chi; Liu, Ren-Shyan

    2002-04-01

    In clinically, structural image based brain tissue segmentation as a preprocess plays an important and essential role on a number of image preprocessing, such as image visualization, object recognition, image registration, and so forth. However, when we need to classify the tissues according to their physiological functions, those strategies are not satisfactory. In this study, we incorporated both tissue time-activity curves (TACs) and derived kinetic parametric curves (KPCs) information to segment brain tissues, such as striatum, gray and white matters, in dynamic FDOPA-PET studies. Four common clustering techniques, K-mean (KM), Fuzzy C-mean (FCM), Isodata (ISO), Markov Random Fields (MRF), and our method were compared to evaluate its precision. The results show 41% and 48% less mean errors in mean difference for KPCs and TACs, respectively, than other methods. Combined KPCs and TACs based clustering method provide the ability to define brain structure effectively.

  15. Effects of scatter on model parameter estimates in 3D PET studies of the human brain

    SciTech Connect

    Cherry, S.R.; Huang, S.C.

    1995-08-01

    Phantom measurements and simulated data were used to characterize the effects of scatter on 3D PET projection data, reconstructed images and model parameter estimates. Scatter distributions were estimated form studies of the 3D Hoffman brain phantom by the 2D/3D difference method. The total scatter fraction in the projection data was 40%, but reduces to 27% when only those counts within the boundary of the brain are considered. After reconstruction, the whole brain scatter fraction is 20%, averaging 10% in cortical gray matter, 21% in basal ganglia and 40% in white matter. The scatter contribution varies by almost a factor of two from the edge to the center of the brain due to the shape of the scatter distribution and the effects of attenuation correction. The effect of scatter on estimates of cerebral metabolic rate for glucose (CMRGI) and cerebral blood flow (CBF) is evaluated by simulating typical gray matter time activity curves (TAC`s) and adding a scatter component based on whole-brain activity. Both CMRGI and CBF change in a linear fashion with scatter fraction. Efforts of between 10 and 30% will typically result if 3D studies are not corrected for scatter. The authors also present results from a simple and fast scatter correction which fits a gaussian function to the scattered events outside the brain. This reduced the scatter fraction to <2% in a range of phantom studies with different activity distributions. Using this correction, quantitative errors in 3D PET studies of CMRGI and CBF can be reduced to well below 10%.

  16. Short-Term Practice Effects and Brain Hypometabolism: Preliminary Data from an FDG PET Study

    PubMed Central

    Duff, Kevin; Horn, Kevin P.; Foster, Norman L.; Hoffman, John M.

    2015-01-01

    Practice effects are improvements in cognitive test scores due to repeated exposure to the same tests. Typically viewed as error, short-term practice effects have been shown to provide valuable clinical information about diagnosis, prognosis, and treatment outcomes in older patients with mild cognitive impairments. This study examined short-term practice effects across one week and brain hypometabolism on fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in 25 older adults (15 intact, 10 Mild Cognitive Impairment). Averaged cerebral brain metabolism on FDG PET was correlated with multiple cognitive scores at baseline in those with Mild Cognitive Impairment, and short-term practice effects accounted for additional variance in these same subjects. The relationship between brain metabolism and cognition (either at baseline or practice effects) was minimal in the intact individuals. Although needing replication in larger samples, short-term practice effects on tests of executive functioning and memory may provide valuable information about biomarkers of Alzheimer’s disease. PMID:25908614

  17. Preserved pontine glucose metabolism in Alzheimer disease: A reference region for functional brain image (PET) analysis

    SciTech Connect

    Minoshima, Satoshi; Frey, K.A.; Foster, N.L.; Kuhl, D.W.

    1995-07-01

    Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative {sup 18}FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. The pons showed the best preservation of glucose metabolism in AD. Other reference regions showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging. 39 refs., 2 figs., 3 tabs.

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

    SciTech Connect

    Kronfeld, Andrea; Müller-Forell, Wibke; Buchholz, Hans-Georg; Maus, Stephan; Reuss, Stefan; Schreckenberger, Mathias; Miederer, Isabelle; Lutz, Beat

    2015-12-15

    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 Dawley 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

  19. PARAQUAT IS EXCLUDED BY THE BLOOD BRAIN BARRIER IN RHESUS MACAQUE: AN IN VIVO PET STUDY

    PubMed Central

    Bartlett, Rachel M.; Holden, James E.; Nickles, R. Jerome; Murali, Dhanabalan; Barbee, David L.; Barnhart, Todd E.; Christian, Bradley C.; DeJesus, Onofre T.

    2009-01-01

    Environmental factors have long been thought to have a role in the etiology of idiopathic Parkinson’s Disease (PD). Since the discovery of the selective neurotoxicity of MPTP to dopamine cells, suspicion has focused on paraquat, a common herbicide with chemical structure similar to 1-methyl-4-phenylpyridinium (MPP+), the MPTP metabolite responsible for its neurotoxicity. Although in vitro evidence for paraquat neurotoxicity to dopamine cells is well established, its in vivo effects have been ambiguous because paraquat is di-cationic in plasma, which raises questions about its ability to cross the blood brain barrier. This study assessed the brain uptake of [11C]-paraquat in adult male rhesus macaques using quantitative PET imaging. Results showed minimal uptake of [11C]-paraquat in the macaque brain. The highest concentrations of paraquat was seen in the pineal gland and the lateral ventricles. Global brain concentrations including those in known dopamine areas were consistent with the blood volume in those structures. This acute exposure study found that paraquat is excluded from the brain by the blood brain barrier and thus does not readily support the causative role of paraquat exposure in idiopathic Parkinson’s Disease. PMID:19135428

  20. Region specific optimization of continuous linear attenuation coefficients based on UTE (RESOLUTE): application to PET/MR brain imaging.

    PubMed

    Ladefoged, Claes N; Benoit, Didier; Law, Ian; Holm, Søren; Kjær, Andreas; Højgaard, Liselotte; Hansen, Adam E; Andersen, Flemming L

    2015-10-21

    The reconstruction of PET brain data in a PET/MR hybrid scanner is challenging in the absence of transmission sources, where MR images are used for MR-based attenuation correction (MR-AC). The main challenge of MR-AC is to separate bone and air, as neither have a signal in traditional MR images, and to assign the correct linear attenuation coefficient to bone. The ultra-short echo time (UTE) MR sequence was proposed as a basis for MR-AC as this sequence shows a small signal in bone. The purpose of this study was to develop a new clinically feasible MR-AC method with patient specific continuous-valued linear attenuation coefficients in bone that provides accurate reconstructed PET image data. A total of 164 [(18)F]FDG PET/MR patients were included in this study, of which 10 were used for training. MR-AC was based on either standard CT (reference), UTE or our method (RESOLUTE). The reconstructed PET images were evaluated in the whole brain, as well as regionally in the brain using a ROI-based analysis. Our method segments air, brain, cerebral spinal fluid, and soft tissue voxels on the unprocessed UTE TE images, and uses a mapping of R(*)2 values to CT Hounsfield Units (HU) to measure the density in bone voxels. The average error of our method in the brain was 0.1% and less than 1.2% in any region of the brain. On average 95% of the brain was within  ±10% of PETCT, compared to 72% when using UTE. The proposed method is clinically feasible, reducing both the global and local errors on the reconstructed PET images, as well as limiting the number and extent of the outliers. PMID:26422177

  1. Region specific optimization of continuous linear attenuation coefficients based on UTE (RESOLUTE): application to PET/MR brain imaging

    NASA Astrophysics Data System (ADS)

    Ladefoged, Claes N.; Benoit, Didier; Law, Ian; Holm, Søren; Kjær, Andreas; Højgaard, Liselotte; Hansen, Adam E.; Andersen, Flemming L.

    2015-10-01

    The reconstruction of PET brain data in a PET/MR hybrid scanner is challenging in the absence of transmission sources, where MR images are used for MR-based attenuation correction (MR-AC). The main challenge of MR-AC is to separate bone and air, as neither have a signal in traditional MR images, and to assign the correct linear attenuation coefficient to bone. The ultra-short echo time (UTE) MR sequence was proposed as a basis for MR-AC as this sequence shows a small signal in bone. The purpose of this study was to develop a new clinically feasible MR-AC method with patient specific continuous-valued linear attenuation coefficients in bone that provides accurate reconstructed PET image data. A total of 164 [18F]FDG PET/MR patients were included in this study, of which 10 were used for training. MR-AC was based on either standard CT (reference), UTE or our method (RESOLUTE). The reconstructed PET images were evaluated in the whole brain, as well as regionally in the brain using a ROI-based analysis. Our method segments air, brain, cerebral spinal fluid, and soft tissue voxels on the unprocessed UTE TE images, and uses a mapping of R2* values to CT Hounsfield Units (HU) to measure the density in bone voxels. The average error of our method in the brain was 0.1% and less than 1.2% in any region of the brain. On average 95% of the brain was within  ±10% of PETCT, compared to 72% when using UTE. The proposed method is clinically feasible, reducing both the global and local errors on the reconstructed PET images, as well as limiting the number and extent of the outliers.

  2. Designing a compact high performance brain PET scanner-simulation study.

    PubMed

    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

    2016-05-21

    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

  3. 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.

  4. FDG-PET/CT Brain Findings in a Patient With Macrophagic Myofasciitis.

    PubMed

    Van Der Gucht, Axel; Aoun-Sebaiti, Mehdi; Kauv, Paul; Guedj, Eric; Aouizerate, Jessie; Verger, Antoine; Gherardi, Romain K; Bachoud-Levi, Anne-Catherine; Authier, François-Jérôme; Itti, Emmanuel

    2016-03-01

    Brain Positron Emission Tomography/Computed Tomography with (18)F-fluorodeoxyglucose (FDG PET/CT) was performed in a 44-year-old woman with marked cognitive impairment, diffuse myalgias, sensory, memory and visual disorders, and chronic fatigue, presenting with histopathological features of macrophagic myofasciitis (MMF) at deltoid muscle biopsy. Cerebromedullary Magnetic Resonance Imaging (MRI), electromyography, ophthalmic examination, and cerebrospinal fluid analysis were normal. Visual analysis of FDG PET/CT images showed an atypical pattern of hypometabolism, involving symmetrically the occipital cortex, temporal lobes, and limbic system (including in particular amygdalo-hippocampal complexes), and the cerebellum. Posterior cingulate cortex and parietal areas were preserved. This pattern was confirmed by a voxel-based procedure using Statistical Parametric Mapping (SPM12) that compared a patient's images to normal reference samples from six healthy subjects with adjustment to age obtained using the same PET/CT camera. These results provide a glucose metabolism substrate for cognitive complaints in patients with long-lasting aluminium hydroxide-induced MMF. PMID:26941864

  5. Ligands for SPECT and PET imaging of muscarinic-cholinergic receptors of the heart and brain

    SciTech Connect

    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 of 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.

  6. A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

    PubMed Central

    Roy, Maggie; Nugent, Scott; Tremblay, Sébastien; Descoteaux, Maxime; Beaudoin, Jean-François; Tremblay, Luc; Lecomte, Roger; Cunnane, Stephen C

    2013-01-01

    We present a method for comparing the uptake of the brain's two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which 11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of 11C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of 11C-AcAc and 18F-FDG brain uptake (cerebral metabolic rate; μmol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases. PMID:24430432

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

    SciTech Connect

    Chen, K.; Reiman, E.M.; Lawson, M.; Yun, L.S.; Bandy, D.

    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 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 administrations, 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 applications 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 us to identify rCBF increases in the anteromedial temporal lobe free from the potentially confounding, combined effects of vascular activity and partial-volume averaging.

  8. Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

    PubMed Central

    Choi, Seok Rye; Golding, Geoff; Zhuang, Zhiping; Zhang, Wei; Lim, Nathaniel; Hefti, Franz; Benedum, Tyler E.; Kilbourn, Michael R.; Skovronsky, Daniel; Kung, Hank F.

    2011-01-01

    β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. Methods In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. Results 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain. PMID:19837759

  9. Evaluation of three MRI-based anatomical priors for quantitative PET brain imaging.

    PubMed

    Vunckx, Kathleen; Atre, Ameya; Baete, Kristof; Reilhac, Anthonin; Deroose, Christophe M; Van Laere, Koen; Nuyts, Johan

    2012-03-01

    In emission tomography, image reconstruction and therefore also tracer development and diagnosis may benefit from the use of anatomical side information obtained with other imaging modalities in the same subject, as it helps to correct for the partial volume effect. One way to implement this, is to use the anatomical image for defining the a priori distribution in a maximum-a-posteriori (MAP) reconstruction algorithm. In this contribution, we use the PET-SORTEO Monte Carlo simulator to evaluate the quantitative accuracy reached by three different anatomical priors when reconstructing positron emission tomography (PET) brain images, using volumetric magnetic resonance imaging (MRI) to provide the anatomical information. The priors are: 1) a prior especially developed for FDG PET brain imaging, which relies on a segmentation of the MR-image (Baete , 2004); 2) the joint entropy-prior (Nuyts, 2007); 3) a prior that encourages smoothness within a position dependent neighborhood, computed from the MR-image. The latter prior was recently proposed by our group in (Vunckx and Nuyts, 2010), and was based on the prior presented by Bowsher (2004). The two latter priors do not rely on an explicit segmentation, which makes them more generally applicable than a segmentation-based prior. All three priors produced a compromise between noise and bias that was clearly better than that obtained with postsmoothed maximum likelihood expectation maximization (MLEM) or MAP with a relative difference prior. The performance of the joint entropy prior was slightly worse than that of the other two priors. The performance of the segmentation-based prior is quite sensitive to the accuracy of the segmentation. In contrast to the joint entropy-prior, the Bowsher-prior is easily tuned and does not suffer from convergence problems. PMID:22049363

  10. A Monte Carlo correction for the effect of Compton scattering in 3-D PET brain imaging

    SciTech Connect

    Levin, C.S.; Dahlbom, M.; Hoffman, E.J.

    1995-08-01

    A Monte Carlo simulation has been developed to simulate and correct for the effect of Compton scatter in 3-D acquired PET brain scans. The method utilizes the 3-D reconstructed image volume as the source intensity distribution for a photon-tracking Monte Carlo simulation. It is assumed that the number of events in each pixel of the image represents the isotope concentration at that location in the brain. The history of each annihilation photon`s interactions in the scattering medium is followed, and the sinograms for the scattered and unscattered photon pairs are generated in a simulated 3-D PET acquisition. The calculated scatter contribution is used to correct the original data set. The method is general and can be applied to any scanner configuration or geometry. In its current form the simulation requires 25 hours on a single Sparc 10 CPU when every pixel in a 15-plane, 128 x 128 pixel image volume is sampled, and less than 2 hours when 16 pixels (4 x 4) are grouped as a single pixel. Results of the correction applied to 3-D human and phantom studies are presented.

  11. Plasma based markers of [11C] PiB-PET brain amyloid burden.

    PubMed

    Kiddle, Steven John; Thambisetty, Madhav; Simmons, Andrew; Riddoch-Contreras, Joanna; Hye, Abdul; Westman, Eric; Pike, Ian; Ward, Malcolm; Johnston, Caroline; Lupton, Michelle Katharine; Lunnon, Katie; Soininen, Hilkka; Kloszewska, Iwona; Tsolaki, Magda; Vellas, Bruno; Mecocci, Patrizia; Lovestone, Simon; Newhouse, Stephen; Dobson, Richard

    2012-01-01

    Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11)C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored. PMID:23028511

  12. Brain metabolic changes in Hodgkin disease patients following diagnosis and during the disease course: An 18F-FDG PET/CT study

    PubMed Central

    CHIARAVALLOTI, AGOSTINO; PAGANI, MARCO; CANTONETTI, MARIA; DI PIETRO, BARBARA; TAVOLOZZA, MARIO; TRAVASCIO, LAURA; DI BIAGIO, DANIELE; DANIELI, ROBERTA; SCHILLACI, ORAZIO

    2015-01-01

    The aim of the present study was to investigate brain glucose metabolism in patients with Hodgkin disease (HD) after diagnosis and during chemotherapy treatment. Following the administration of first-line doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography brain scans, both baseline (PET0) and interim (PET2) at the Department of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy). Fifty-seven patients were further evaluated 15±6 days after four additional cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naïve subjects was enrolled. Differences in brain 18F-FDG uptake between the CG, PET0, PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally and in left BA 32. All of these changes disappeared at PET6. The results of the present study indicate that ABVD chemotherapy has a limited impact on brain metabolism. PMID:25621038

  13. Optimising PET approaches to measuring 5-HT release in human brain.

    PubMed

    Tyacke, Robin J; Nutt, David J

    2015-10-01

    A major goal in neuroscience is the measurement of neurotransmitters in living human brain. To date this has only been done reliably with dopamine using certain PET and SPECT radiotracers. The use of this technique has greatly advanced our understanding of dopamine and the dopaminergic system in normal and abnormal brain function. Transferring this technology to other neurotransmitter systems has proved less fruitful. The serotonergic system (5-HT) is one such system. 5-HT has been implicated in a wide range of brain functions and their disorders. The ability to measure 5-HT using this technique would be invaluable. In this article, we explore the key pharmacological features of current radiotracers for 5-HT receptors that might be sensitive to endogenous 5-HT. We also estimate the likely brain concentrations of the current available tranche of agents that might be used to enhance synaptic 5-HT concentration, so taking into account the potential for these to interact with the receptors directly and produce a spurious displacement signal. PMID:26089243

  14. Brain areas involved in the acupuncture treatment of AD model rats: a PET study

    PubMed Central

    2014-01-01

    Background Acupuncture may effectively treat certain symptoms of Alzheimer’s disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model. Methods A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2. Results The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe. Conclusion We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients. PMID:24886495

  15. A Multi-Atlas Based Method for Automated Anatomical Rat Brain MRI Segmentation and Extraction of PET Activity

    PubMed Central

    Lancelot, Sophie; Roche, Roxane; Slimen, Afifa; Bouillot, Caroline; Levigoureux, Elise; Langlois, Jean-Baptiste; Zimmer, Luc; Costes, Nicolas

    2014-01-01

    Introduction Preclinical in vivo imaging requires precise and reproducible delineation of brain structures. Manual segmentation is time consuming and operator dependent. Automated segmentation as usually performed via single atlas registration fails to account for anatomo-physiological variability. We present, evaluate, and make available a multi-atlas approach for automatically segmenting rat brain MRI and extracting PET activies. Methods High-resolution 7T 2DT2 MR images of 12 Sprague-Dawley rat brains were manually segmented into 27-VOI label volumes using detailed protocols. Automated methods were developed with 7/12 atlas datasets, i.e. the MRIs and their associated label volumes. MRIs were registered to a common space, where an MRI template and a maximum probability atlas were created. Three automated methods were tested: 1/registering individual MRIs to the template, and using a single atlas (SA), 2/using the maximum probability atlas (MP), and 3/registering the MRIs from the multi-atlas dataset to an individual MRI, propagating the label volumes and fusing them in individual MRI space (propagation & fusion, PF). Evaluation was performed on the five remaining rats which additionally underwent [18F]FDG PET. Automated and manual segmentations were compared for morphometric performance (assessed by comparing volume bias and Dice overlap index) and functional performance (evaluated by comparing extracted PET measures). Results Only the SA method showed volume bias. Dice indices were significantly different between methods (PF>MP>SA). PET regional measures were more accurate with multi-atlas methods than with SA method. Conclusions Multi-atlas methods outperform SA for automated anatomical brain segmentation and PET measure’s extraction. They perform comparably to manual segmentation for FDG-PET quantification. Multi-atlas methods are suitable for rapid reproducible VOI analyses. PMID:25330005

  16. 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. PMID:27117985

  17. ImmunoPET Imaging of CD146 Expression in Malignant Brain Tumors.

    PubMed

    Hernandez, Reinier; Sun, Haiyan; England, Christopher G; Valdovinos, Hector F; Barnhart, Todd E; Yang, Yunan; Cai, Weibo

    2016-07-01

    Recently, the overexpression of CD146 and its potential as a therapeutic target in high-grade gliomas, the most lethal type of brain cancer, was uncovered. In this study, we describe the generation of (89)Zr-Df-YY146, a novel (89)Zr-labeled monoclonal antibody (mAb) for the targeting and quantification of CD146 expression in a mouse model of glioblastoma, using noninvasive immunoPET imaging. YY146, a high affinity anti-CD146 mAb, was conjugated to deferoxamine (Df) for labeling with the long-lived positron emitter (89)Zr (t1/2: 78.4 h). In vitro assays, including flow cytometry, immunofluorescence microscopy, and Western blot, were performed with two glioblastoma cell lines, U87MG and U251, to determine their CD146 expression levels. Also, YY146 and Df-YY146's CD146-binding affinities were compared using flow cytometry. In vivo CD146-targeting of (89)Zr-Df-YY146 was evaluated by sequential PET imaging, in athymic nude mice bearing subcutaneously implanted U87MG or U251 tumors. CD146 blocking, ex vivo biodistribution, and histological studies were carried out to confirm (89)Zr-Df-YY146 specificity, as well as the accuracy of PET data. In vitro studies exposed elevated CD146 expression levels in U87MG cells, but negligible levels in U251 cells. Flow cytometry revealed no differences in affinity between YY146 and Df-YY146. (89)Zr labeling of Df-YY146 proceeded with excellent yield (∼80%), radiochemical purity (>95%), and specific activity (∼44 GBq/μmol). Longitudinal PET revealed prominent and persistent (89)Zr-Df-YY146 uptake in mice bearing U87MG tumors that peaked at 14.00 ± 3.28%ID/g (n = 4), 48 h post injection of the tracer. Conversely, uptake was significantly lower in CD146-negative U251 tumors (5.15 ± 0.99%ID/g, at 48 h p.i.; n = 4; P < 0.05). Uptake in U87MG tumors was effectively blocked in a competitive inhibition experiment, corroborating the CD146 specificity of (89)Zr-Df-YY146. Finally, ex vivo biodistribution validated the accuracy of PET data

  18. Quantitative imaging of protein targets in the human brain with PET.

    PubMed

    Gunn, Roger N; Slifstein, Mark; Searle, Graham E; Price, Julie C

    2015-11-21

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  19. Quantitative imaging of protein targets in the human brain with PET

    NASA Astrophysics Data System (ADS)

    Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

    2015-11-01

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  20. Positron emission tomography (PET) studies of dopaminergic/cholinergic interactions in the baboon brain

    SciTech Connect

    Dewey, S.L.; Brodie, J.D.; Fowler, J.S.; MacGregor, R.R.; Schlyer, D.J.; King, P.T.; Alexoff, D.L.; Volkow, N.D.; Shiue, C.Y.; Wolf, A.P. )

    1990-01-01

    Interactions between the dopaminergic D2 receptor system and the muscarinic cholinergic system in the corpus striatum of adult female baboons (Papio anubis) were examined using positron emission tomography (PET) combined with (18F)N-methylspiroperidol (( 18F)NMSP) (to probe D2 receptor availability) and (N-11C-methyl)benztropine (to probe muscarinic cholinergic receptor availability). Pretreatment with benztropine, a long-lasting anticholinergic drug, bilaterally reduced the incorporation of radioactivity in the corpus striatum but did not alter that observed in the cerebellum or the rate of metabolism of (18F)NMSP in plasma. Pretreatment with unlabelled NMSP, a potent dopaminergic antagonist, reduced the incorporation of (N-11C-methyl)benztropine in all brain regions, with the greatest effect being in the corpus striatum greater than cortex greater than thalamus greater than cerebellum, but did not alter the rate of metabolism of the labelled benztropine in the plasma. These reductions in the incorporation of either (18F)NMSP or (N-11C-methyl)benztropine exceeded the normal variation in tracer incorporation in repeated studies in the same animal. This study demonstrates that PET can be used as a tool for investigating interactions between neurochemically different yet functionally linked neurotransmitters systems in vivo and provides insight into the consequences of multiple pharmacologic administration.

  1. Marker-less multi-frame motion tracking and compensation in PET-brain imaging

    NASA Astrophysics Data System (ADS)

    Lindsay, C.; Mukherjee, J. M.; Johnson, K.; Olivier, P.; Song, X.; Shao, L.; King, M. A.

    2015-03-01

    In PET brain imaging, patient motion can contribute significantly to the degradation of image quality potentially leading to diagnostic and therapeutic problems. To mitigate the image artifacts resulting from patient motion, motion must be detected and tracked then provided to a motion correction algorithm. Existing techniques to track patient motion fall into one of two categories: 1) image-derived approaches and 2) external motion tracking (EMT). Typical EMT requires patients to have markers in a known pattern on a rigid too attached to their head, which are then tracked by expensive and bulky motion tracking camera systems or stereo cameras. This has made marker-based EMT unattractive for routine clinical application. Our main contributions are the development of a marker-less motion tracking system that uses lowcost, small depth-sensing cameras which can be installed in the bore of the imaging system. Our motion tracking system does not require anything to be attached to the patient and can track the rigid transformation (6-degrees of freedom) of the patient's head at a rate 60 Hz. We show that our method can not only be used in with Multi-frame Acquisition (MAF) PET motion correction, but precise timing can be employed to determine only the necessary frames needed for correction. This can speeds up reconstruction by eliminating the unnecessary subdivision of frames.

  2. Dixon sequence with superimposed model-based bone compartment provides highly accurate PET/MR attenuation correction of the brain

    PubMed Central

    Koesters, Thomas; Friedman, Kent P.; Fenchel, Matthias; Zhan, Yiqiang; Hermosillo, Gerardo; Babb, James; Jelescu, Ileana O.; Faul, David; Boada, Fernando E.; Shepherd, Timothy M.

    2016-01-01

    Simultaneous PET/MR of the brain is a promising new technology for characterizing patients with suspected cognitive impairment or epilepsy. Unlike CT though, MR signal intensities do not provide a direct correlate to PET photon attenuation correction (AC) and inaccurate radiotracer standard uptake value (SUV) estimation could limit future PET/MR clinical applications. We tested a novel AC method that supplements standard Dixon-based tissue segmentation with a superimposed model-based bone compartment. Methods We directly compared SUV estimation for MR-based AC methods to reference CT AC in 16 patients undergoing same-day, single 18FDG dose PET/CT and PET/MR for suspected neurodegeneration. Three Dixon-based MR AC methods were compared to CT – standard Dixon 4-compartment segmentation alone, Dixon with a superimposed model-based bone compartment, and Dixon with a superimposed bone compartment and linear attenuation correction optimized specifically for brain tissue. The brain was segmented using a 3D T1-weighted volumetric MR sequence and SUV estimations compared to CT AC for whole-image, whole-brain and 91 FreeSurfer-based regions-of-interest. Results Modifying the linear AC value specifically for brain and superimposing a model-based bone compartment reduced whole-brain SUV estimation bias of Dixon-based PET/MR AC by 95% compared to reference CT AC (P < 0.05) – this resulted in a residual −0.3% whole-brain mean SUV bias. Further, brain regional analysis demonstrated only 3 frontal lobe regions with SUV estimation bias of 5% or greater (P < 0.05). These biases appeared to correlate with high individual variability in the frontal bone thickness and pneumatization. Conclusion Bone compartment and linear AC modifications result in a highly accurate MR AC method in subjects with suspected neurodegeneration. This prototype MR AC solution appears equivalent than other recently proposed solutions, and does not require additional MR sequences and scan time. These

  3. NEMA and clinical evaluation of a novel brain PET-CT scanner

    PubMed Central

    Grogg, Kira S.; Toole, Terrence; Ouyang, Jinsong; Zhu, Xuping; Normandin, Marc; Johnson, Keith; Alpert, Nathaniel M.; Fakhri, Georges El

    2016-01-01

    The aim of this study was to determine the performance of a novel mobile human brain/small animal PET-CT system, developed by Photo Diagnostic Systems Inc. The scanner has a 35.7-cm diameter bore and a 22-cm axial extent. The detector ring has 7 modules each with 3×4 cerium-doped lutetium yttrium orthosilicate crystal blocks, each consisting of 22×22 outer layer and 21×21 inner layer crystals, each layer 1 cm thick. Light is collected by 12×12 SiPMs. The integrated CT can be used for attenuation correction and anatomical localization. The scanner was designed as a low-cost device that nevertheless produces high-quality PET images with the unique capability of battery-powered propulsion, enabling use in many settings. Methods Spatial resolution, sensitivity and noise-equivalent count rate (NECR) were measured based on the National Electrical Manufacturers Association NU2-2012 procedures. Reconstruction was done with tight energy and timing cuts: 400-650 keV and 7ns, and loose cuts: 350-700 keV and 10ns. Additional image quality measurements were made from phantoms, human, and animal studies. Performance was compared to a reference scanner (ECAT Exact HR+) with comparable imaging properties. Results The full-width half-max transverse resolution at 1 cm (10 cm) radius is 3.2 mm (5.2 mm radial, 3.1 mm tangential) and the axial resolution is 3.5 mm (4.0 mm). For tight (loose) cuts, a sensitivity of 7.5 (11.7) kcps/MBq at the center increases to 8.8 (13.9) kcps/MBq at a 10 cm radial offset. The maximum NECR of 19.5 (22.7) kcps was achieved for an activity concentration of 2.9 kBq/ml. Contrast recovery for 4:1 hot cylinder to warm background was 76% for the 25 mm diameter cylinder, but decreased with decreasing cylinder size. The quantitation agrees within 2% of the known activity distribution and concentration. Brain phantom and human scans have shown agreement in SUV values and image quality with the HR+. Conclusion We have characterized the performance of the NeuroPET

  4. Comparative study of 18F-DOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors

    PubMed Central

    Jacob, Mattakarottu J; Pandit, Aniruddha G; Jora, Charu; Mudalsha, Ravina; Sharma, Amit; Pathak, Harish C

    2011-01-01

    Aim: To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors. We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT. Materials and Methods: Nine patients undergoing evaluation for brain tumors were studied. Tracer uptake was quantified by the use of standardized uptake values and the ratio of tumor uptake to normal identical area of contra lateral hemisphere (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratio of tumor uptake to striatum uptake (T/S). The results were correlated with the patient's clinical profile. Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with F18-FDG and 13N-Ammonia PET as determined by simple visual inspection. The sensitivity for identifying recurrence in low grade gliomas is higher with 13N-Ammonia than with F18-FDG. Conclusion: 18F-FDOPA PET is more reliable than F18-FDG and 13N-Ammonia PET for evaluating brain tumors. PMID:23326065

  5. PET Quantification of Cerebral Oxygen Metabolism in Small Animals

    PubMed Central

    Temma, Takashi; Koshino, Kazuhiro; Moriguchi, Tetsuaki; Enmi, Jun-ichiro; Iida, Hidehiro

    2014-01-01

    Understanding cerebral oxygen metabolism is of great importance in both clinical diagnosis and animal experiments because oxygen is a fundamental source of brain energy and supports brain functional activities. Since small animals such as rats are widely used to study various diseases including cerebral ischemia, cerebrovascular diseases, and neurodegenerative diseases, the development of a noninvasive in vivo measurement method of cerebral oxygen metabolic parameters such as oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as cerebral blood flow (CBF) and cerebral blood volume (CBV) has been a priority. Although positron emission tomography (PET) with 15O labeled gas tracers has been recognized as a powerful way to evaluate cerebral oxygen metabolism in humans, this method could not be applied to rats due to technical problems and there were no reports of PET measurement of cerebral oxygen metabolism in rats until an 15O-O2 injection method was developed a decade ago. Herein, we introduce an intravenous administration method using two types of injectable 15O-O2 and an 15O-O2 gas inhalation method through an airway placed in the trachea, which enables oxygen metabolism measurements in rats. PMID:25202714

  6. Statistical analysis of maximum likelihood estimator images of human brain FDG PET studies

    SciTech Connect

    Llacer, J.; Veklerov, E. ); Hoffman, E.J. . Dept. of Radiological Sciences); Nunez, J. , Facultat de Fisica); Coakley, K.J.

    1993-06-01

    The work presented in this paper evaluates the statistical characteristics of regional bias and expected error in reconstructions of real PET data of human brain fluorodeoxiglucose (FDG) studies carried out by the maximum likelihood estimator (MLE) method with a robust stopping rule, and compares them with the results of filtered backprojection (FBP) reconstructions and with the method of sieves. The task that the authors have investigated is that of quantifying radioisotope uptake in regions-of-interest (ROI's). They first describe a robust methodology for the use of the MLE method with clinical data which contains only one adjustable parameter: the kernel size for a Gaussian filtering operation that determines final resolution and expected regional error. Simulation results are used to establish the fundamental characteristics of the reconstructions obtained by out methodology, corresponding to the case in which the transition matrix is perfectly known. Then, data from 72 independent human brain FDG scans from four patients are used to show that the results obtained from real data are consistent with the simulation, although the quality of the data and of the transition matrix have an effect on the final outcome.

  7. Factors affecting bilateral temporal lobe hypometabolism on 18F-FDG PET brain scan in unilateral medial temporal lobe epilepsy.

    PubMed

    Tepmongkol, Supatporn; Srikijvilaikul, Teeradej; Vasavid, Pataramon

    2013-11-01

    Bilateral temporal lobe hypometabolism (BTH) on (18)F-FDG PET brain scan is frequently seen in unilateral medial temporal lobe epilepsy (mTLE). This study aimed to identify the factors that influence BTH in patients with mTLE in order to minimize the significant factor(s) prior to performing a FDG-PET brain scan. Forty patients with unilateral mTLE who underwent (18)F-FDG PET scan for presurgical epilepsy workup were included. Bilateral temporal lobe hypometabolism of the anterior and medial parts of the temporal lobe was identified by a semiquantitative visual scale. Lateralization of TLE was identified by either intracranial EEG (22/40 cases) and/or improvement of seizure 2 years after temporal lobectomy (37/40 cases). The factors analyzed included basic demographic characteristics (age, sex, occupation, years of education, and handedness), history related to seizure (age at epilepsy onset and epilepsy duration, history of febrile seizure and head injury, frequency of seizure with impaired cognition in the last 3 months, presence of secondarily generalized tonic-clonic seizure, automatism side, presence of postictal confusion, and side of MRI temporal abnormality), information during video-EEG monitoring (clinical lateralization, interictal scalp EEG lateralization (interictal epileptiform discharge), and ictal scalp EEG lateralization), and information during the FDG-PET study (duration from the last seizure (≤2 days or >2 days), last seizure type, and the presence of slow waves or sharp waves during the FDG uptake period). Significant factors related to BTH were analyzed using multivariate analysis. Only the ≤2-day duration from the last seizure to the PET scan shows a significant effect (p=0.021) on BTH finding with 15 times greater incidence compared to a duration >2 days. Bilateral temporal lobe hypometabolism, which causes conflict in lateralizing the epileptogenic zone in temporal lobe epilepsy, can be avoided by performing PET scan more than 2 days

  8. PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS

    PubMed Central

    Venneti, Sriram; Lopresti, Brian J.; Wang, Guoji; Bissel, Stephanie J.; Mathis, Chester A.; Meltzer, Carolyn C.; Boada, Fernando; Capuano, Saverio; Kress, Geraldine J.; Davis, Denise K.; Ruszkiewicz, James; Reynolds, Ian J.; Murphey-Corb, Michael; Trichel, Anita M.; Wisniewski, Stephen R.; Wiley, Clayton A.

    2004-01-01

    HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques result in encephalitis in approximately one-quarter of infected individuals and is characterized by infiltration of the brain with infected and activated macrophages. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (PK11195) is a ligand specific for the peripheral benzodiazepine receptor abundant on macrophages and is expressed in low levels in the noninfected brain. We hypothesized that positron-emission tomography (PET) with the carbon-11–labeled, R-enantiomer form of PK11195 ([11C](R)-PK11195) could image brain macrophages and hence the development of encephalitis in vivo. [11C](R)-PK11195 binding was assessed in the brain using PET in 11 SIV infected macaques, six of which showed increased binding in vivo. Postmortem examination of the brain in these six macaques demonstrated encephalitis, while macaques that did not show an increase in [11C](R)-PK11195 binding did not develop SIV encephalitis. Brain tissue from SIV encephalitic macaques also showed increased [3H](R)-PK11195 binding compared with binding in nonencephalitic macaques. Increased PK11195 binding in vivo and in postmortem brain tissue correlated with abundance of macrophages but not astrocytes. Our results suggest that PET [11C](R)-PK11195 imaging can detect the presence of macrophages in SIV encephalitis in vivo and may be useful to predict the development of HIV encephalitis and in studies of the pathogenesis and treatment of HIV dementia. PMID:15057304

  9. The Sum of Tumour-to-Brain Ratios Improves the Accuracy of Diagnosing Gliomas Using 18F-FET PET

    PubMed Central

    Zyromska, Agnieszka; Wisniewski, Tomasz; Harat, Aleksandra; Lopatto, Rita; Furtak, Jacek

    2015-01-01

    Gliomas are common brain tumours, but obtaining tissue for definitive diagnosis can be difficult. There is, therefore, interest in the use of non-invasive methods to diagnose and grade the disease. Although positron emission tomography (PET) with 18F-fluorethyltyrosine (18F-FET) can be used to differentiate between low-grade (LGG) and high-grade (HGG) gliomas, the optimal parameters to measure and their cut-points have yet to be established. We therefore assessed the value of single and dual time-point acquisition of 18F-FET PET parameters to differentiate between primary LGGs (n = 22) and HGGs (n = 24). PET examination was considered positive for glioma if the metabolic activity was 1.6-times higher than that of background (contralateral) brain, and maximum tissue-brain ratios (TBRmax) were calculated 10 and 60 min after isotope administration with their sums and differences calculated from individual time-point values. Using a threshold-based method, the overall sensitivity of PET was 97%. Several analysed parameters were significantly different between LGGs and HGGs. However, in a receiver operating characteristics analysis, TBR sum had the best diagnostic accuracy of 87% and sensitivity, specificity, and positive and negative predictive values of 100%, 72.7%, 80%, and 100%, respectively. 18F-FET PET is valuable for the non-invasive determination of glioma grade, especially when dual time-point metrics are used. TBR sum shows the greatest accuracy, sensitivity, and negative predictive value for tumour grade differentiation and is a simple method to implement. However, the cut-off may differ between institutions and calibration strategies would be useful. PMID:26468649

  10. Statistical Voxel-Based Methods and [18F]FDG PET Brain Imaging: Frontiers for the Diagnosis of AD.

    PubMed

    Gallivanone, Francesca; Della Rosa, Pasquale Anthony; Castiglioni, Isabella

    2016-01-01

    Recommended guidelines for the diagnosis of dementia due to Alzheimer's Disease (AD) were revised in recent years, including Positron Emission Tomography (PET) as an in-vivo diagnostic imaging technique for the diagnosis of neurodegeneration. In particular PET, using 18Ffluorodeoxiglucouse ([18F]FDG), is able to detect very early changes of glucose consumption at the synaptic level, enabling to support both early and differential diagnosis of AD. In standard clinical practice, interpretation of [18F] FDG-PET images is usually achieved through qualitative assessment. Visual inspection although only reveals information visible at human eyes resolution, while information at a higher resolution is missed. Furthermore, qualitative assessment depends on the degree of expertise of the clinician, preventing from the definition of accurate and standardized imaging biomarkers. Automated and computerized image processing methods have been proposed to support the in-vivo assessment of brain PET studies. In particular, objective statistical image analyses, enabling the comparison of one patient's images to a group of control images have been shown to carry important advantages for detecting significant metabolic changes, including the availability of more objective, cross-center reliable metrics and the detectability of brain subtle functional changes, as occurring in prodromal AD. The purpose of the current review is to provide a systematic overview encompassing the frontiers recently reached by quantitative approaches for the statistical analysis of PET brain images in the study of AD, with a particular focus on Statistical Parametric Mapping. Main achievements, e.g. in terms of standardized biomarkers of AD as well as of sensitivity and specificity, will be discussed. PMID:26567733

  11. Can brain thallium 201 SPECT substitute for F-18-FDG PET in detecting recurrent brain tumor in the presence of radiation necrosis; correlation with biopsy/surgery results

    SciTech Connect

    Antar, M.A.; Barnett, G.H.; McIntyre, W.J.

    1994-05-01

    F-18-FDG PET man has been largely successful in differentiating between radiation necrosis and recurrent brain tumors. Because of the expense and unavailability of PET scanners in most clinical centers, Tl-201 SPECT scan may offer an alternative. Therefore, we have evaluated both techniques in 18 patients (13 men and 5 women) whose ages range from 28 to 74 year old. Eleven patients had glioblastoma multiformi and 4 patients high grade astrocytoma and 3 patient meningiosarcoma. All patients received radiation therapy (5500-6000 Rad) and 13 patients received also chemotherapy. PET scan was performed 40-60 min. after 5-10 mCi of F-18 FDG (i.v.) and SPECT 30 min. after 4.6 mCi of Tl-201 chloride (i.v.). Severe FDG hypometabolism was evident in the irradiated regions, in all patients. Evidence of tumor recurrence was seen in 15 patients by both FDG PET and Thallium 201 SPECT. The ratio of peak pixel uptake of suspected tumor to that of normal cortex for FDG ranged from 0.67 to 1.5 with a mean of 1.02. The ratio of peak pixel uptake of thallium 201 in the suspected lesion to that of the contralateral scalp area ranges from 0.8 to 1.9 with mean of 1.1. There was concordance between the findings of PET and SPECT in 16/18 patients. However, the volume of involvement differs in these patients; most likely secondary to different mechanisms of uptake and both studies may complement each other. Subsequent biopsy/surgery in 11 patients confirmed tumor recurrence in 10 out of 11 patients. The findings suggest that thallium 201 brain SPECT scan can provide similar (but not identical) information regarding brain tumor recurrence in these patients.

  12. FDG-PET mapping the brain substrates of visuo-constructive processing in Alzheimer's disease.

    PubMed

    Förster, Stefan; Teipel, Stefan; Zach, Christian; Rominger, Axel; Cumming, Paul; Fougere, Christian la; Yakushev, Igor; Haslbeck, Marianne; Hampel, Harald; Bartenstein, Peter; Bürger, Katharina

    2010-05-01

    The anatomical basis of visuo-constructive impairment in AD is widely unexplored. FDG-PET can be used to determine functional neuronal networks underlying specific cognitive performance in the human brain. In the present study, we determined the pattern of cortical metabolism that was associated with visuo-constructive performance in AD. We employed two widely used visuo-constructive tests that differ in their demand on visual perception and processing capacity. Resting state FDG-PET scans were obtained in 29 probable AD patients, and cognitive tests were administered. We made a voxel-based regression analysis of FDG uptake to scores in visual test performance, using the SPM5 software. Performance in the CERAD Drawing test correlated with FDG uptake in the bilateral inferior temporal gyri, bilateral precuneus, right cuneus, right supramarginal gyrus and right middle temporal gyrus covering areas of dorsal and ventral visual streams. In contrast, performance in the more complex RBANS Figure Copy test correlated with FDG uptake in the bilateral fusiform gyri, right inferior temporal gyrus, left anterior cingulate gyrus, left parahippocampal gyrus, right middle temporal gyrus and right insula, encompassing the ventral visual stream and areas of higher-level visual processing. The study revealed neuronal networks underlying impaired visual test performance in AD. The extent of involvement of visual and higher order association cortex increased with greater test complexity. From a clinical point of view, both of these widely used visual tests evaluate the integrity of complementary cortical networks and may contribute complementary information on the integrity of visual processing in AD. PMID:19875130

  13. Toward noninvasive quantification of brain radioligand binding by combining electronic health records and dynamic PET imaging data.

    PubMed

    Mikhno, Arthur; Zanderigo, Francesca; Todd Ogden, R; John Mann, J; Angelini, Elsa D; Laine, Andrew F; Parsey, Ramin V

    2015-07-01

    Quantitative analysis of positron emission tomography (PET) brain imaging data requires a metabolite-corrected arterial input function (AIF) for estimation of distribution volume and related outcome measures. Collecting arterial blood samples adds risk, cost, measurement error, and patient discomfort to PET studies. Minimally invasive AIF estimation is possible with simultaneous estimation (SIME), but at least one arterial blood sample is necessary. In this study, we describe a noninvasive SIME (nSIME) approach that utilizes a pharmacokinetic input function model and constraints derived from machine learning applied to an electronic health record database consisting of "long tail" data (digital records, paper charts, and handwritten notes) that were collected ancillary to the PET studies. We evaluated the performance of nSIME on 95 [(11)C]DASB PET scans that had measured AIFs. The results indicate that nSIME is a promising alternative to invasive AIF measurement. The general framework presented here may be expanded to other metabolized radioligands, potentially enabling quantitative analysis of PET studies without blood sampling. A glossary of technical abbreviations is provided at the end of this paper. PMID:25823051

  14. Regional brain distribution of translocator protein using [(11)C]DPA-713 PET in individuals infected with HIV.

    PubMed

    Coughlin, Jennifer M; Wang, Yuchuan; Ma, Shuangchao; Yue, Chen; Kim, Pearl K; Adams, Ashley V; Roosa, Heidi V; Gage, Kenneth L; Stathis, Marigo; Rais, Rana; Rojas, Camilo; McGlothan, Jennifer L; Watkins, Crystal C; Sacktor, Ned; Guilarte, Tomas R; Zhou, Yun; Sawa, Akira; Slusher, Barbara S; Caffo, Brian; Kassiou, Michael; Endres, Christopher J; Pomper, Martin G

    2014-06-01

    Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [(11)C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [(11)C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test-retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings. PMID:24567030

  15. 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

  16. Metabolic Brain Covariant Networks as Revealed by FDG-PET with Reference to Resting-State fMRI Networks

    PubMed Central

    Di, Xin

    2012-01-01

    Abstract The human brain is inherently organized as separate networks, as has been widely revealed by resting-state functional magnetic resonance imaging (fMRI). Although the large-scale functional connectivity can be partially explained by the underlying white-matter structural connectivity, the question of whether the underlying functional connectivity is related to brain metabolic factors is still largely unanswered. The present study investigated the presence of metabolic covariant networks across subjects using a set of fluorodeoxyglucose (18F, FDG) positron-emission tomography (PET) images. Spatial-independent component analysis was performed on the subject series of FDG-PET images. A number of networks that were mainly homotopic regions could be identified, including visual, auditory, motor, cerebellar, and subcortical networks. However, the anterior-posterior networks such as the default-mode and left frontoparietal networks could not be observed. Region-of-interest-based correlation analysis confirmed that the intersubject metabolic covariances within the default-mode and left frontoparietal networks were reduced as compared with corresponding time-series correlations using resting-state fMRI from an independent sample. In contrast, homotopic intersubject metabolic covariances observed using PET were comparable to the corresponding fMRI resting-state time-series correlations. The current study provides preliminary illustration, suggesting that the human brain metabolism pertains to organized covariance patterns that might partially reflect functional connectivity as revealed by resting-state blood oxygen level dependent (BOLD). The discrepancy between the PET covariance and BOLD functional connectivity might reflect the differences of energy consumption coupling and ongoing neural synchronization within these brain networks. PMID:23025619

  17. Evaluation of the Dopamine Hypothesis of ADHD with PET Brain Imaging

    SciTech Connect

    Swanson, James

    2010-04-28

    The Dopamine (DA) Hypothesis of ADHD (Wender, 1971; Levy, 1990) suggests that abnormalities in the synaptic mechanisms of DA transmission may be disrupted, and specific abnormalities in DA receptors and DA transporters (DAT) have been proposed (see Swanson et al, 1998). Early studies with small samples (e.g., n = 6, Dougherty et al, 1999) used single photon emission tomography (SPECT) and the radioligand (123I Altropane) to test a theory that ADHD may be caused by an over expression of DAT and reported 'a 70% increase in age-corrected dopamine transporter density in patients with attention deficit hyperactivity disorder compared with healthy controls' and suggested that treatment with stimulant medication decreased DAT density in ADHD patients and corrected an underlying abnormality (Krause et al, 2000). The potential importance of these findings was noted by Swanson (1999): 'If true, this is a major finding and points the way for new investigations of the primary pharmacological treatment for ADHD (with the stimulant drugs - e.g., methylphenidate), for which the dopamine transporter is the primary site of action. The potential importance of this finding demands special scrutiny'. This has been provided over the past decade using Positron Emission Tomography (PET). Brain imaging studies were conducted at Brookhaven National Laboratory (BNL) in a relatively large sample of stimulant-naive adults assessed for DAT (11C cocaine) density and DA receptors (11C raclopride) availability. These studies (Volkow et al, 2007; Volkow et al, 2009) do not confirm the hypothesis of increased DAT density and suggest the opposite (i.e., decreased rather than increased DAT density), and follow-up after treatment (Wang et al, 2010) does not confirm the hypothesis that therapeutic doses of methylphenidate decrease DAT density and suggests the opposite (i.e., increased rather than decreased DAT density). The brain regions implicated by these PET imaging studies also suggest that a

  18. Evaluation of the Dopamine Hypothesis of ADHD with PET Brain Imaging

    ScienceCinema

    Swanson, James [University of California, Irvine, California, United States

    2010-09-01

    The Dopamine (DA) Hypothesis of ADHD (Wender, 1971; Levy, 1990) suggests that abnormalities in the synaptic mechanisms of DA transmission may be disrupted, and specific abnormalities in DA receptors and DA transporters (DAT) have been proposed (see Swanson et al, 1998). Early studies with small samples (e.g., n = 6, Dougherty et al, 1999) used single photon emission tomography (SPECT) and the radioligand (123I Altropane) to test a theory that ADHD may be caused by an over expression of DAT and reported 'a 70% increase in age-corrected dopamine transporter density in patients with attention deficit hyperactivity disorder compared with healthy controls' and suggested that treatment with stimulant medication decreased DAT density in ADHD patients and corrected an underlying abnormality (Krause et al, 2000). The potential importance of these findings was noted by Swanson (1999): 'If true, this is a major finding and points the way for new investigations of the primary pharmacological treatment for ADHD (with the stimulant drugs - e.g., methylphenidate), for which the dopamine transporter is the primary site of action. The potential importance of this finding demands special scrutiny'. This has been provided over the past decade using Positron Emission Tomography (PET). Brain imaging studies were conducted at Brookhaven National Laboratory (BNL) in a relatively large sample of stimulant-naive adults assessed for DAT (11C cocaine) density and DA receptors (11C raclopride) availability. These studies (Volkow et al, 2007; Volkow et al, 2009) do not confirm the hypothesis of increased DAT density and suggest the opposite (i.e., decreased rather than increased DAT density), and follow-up after treatment (Wang et al, 2010) does not confirm the hypothesis that therapeutic doses of methylphenidate decrease DAT density and suggests the opposite (i.e., increased rather than decreased DAT density). The brain regions implicated by these PET imaging studies also suggest that a

  19. Design and evaluation of objective methods for analyzing hypometabolism from PET FDG brain images while taking into account finite resolution effects

    SciTech Connect

    Faber, T.L.; Galt, J.R.; Votaw, J.R. |

    1994-05-01

    Objective analyses of positron emission tomographic (PET) FDG brain metabolism studies are complicated by intersubject anatomical differences as well as finite resolution effects within patents. The goal of this study was to design and test techniques that could duplicate the diagnostic interpretation of PET FDG brain studies by clinicians. The clinicians had access to both PET and magnetic resonance images (MRI) of each patent and could discriminate physiological from anatomical effects. The methods create a predicted normal cortical metabolic (PM) image for each individual from his MRI. The PM is compared to actual count levels seen in the PET image. The PM incorporates resolution effects, but not physiological anomalies; the PET image incorporates both. Thus, comparisons between them should highlight physiological differences.

  20. Development of a New Radiofluorinated Quinoline Analog for PET Imaging of Phosphodiesterase 5 (PDE5) in Brain

    PubMed Central

    Liu, Jianrong; Wenzel, Barbara; Dukic-Stefanovic, Sladjana; Teodoro, Rodrigo; Ludwig, Friedrich-Alexander; Deuther-Conrad, Winnie; Schröder, Susann; Chezal, Jean-Michel; Moreau, Emmanuel; Brust, Peter; Maisonial-Besset, Aurélie

    2016-01-01

    Phosphodiesterases (PDEs) are enzymes that play a major role in cell signalling by hydrolysing the secondary messengers cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) throughout the body and brain. Altered cyclic nucleotide-mediated signalling has been associated with a wide array of disorders, including neurodegenerative disorders. Recently, PDE5 has been shown to be involved in neurodegenerative disorders such as Alzheimer’s disease, but its precise role has not been elucidated yet. To visualize and quantify the expression of this enzyme in brain, we developed a radiotracer for specific PET imaging of PDE5. A quinoline-based lead compound has been structurally modified resulting in the fluoroethoxymethyl derivative ICF24027 with high inhibitory activity towards PDE5 (IC50 = 1.86 nM). Radiolabelling with fluorine-18 was performed by a one-step nucleophilic substitution reaction using a tosylate precursor (RCY(EOB) = 12.9% ± 1.8%; RCP > 99%; SA(EOS) = 70–126 GBq/μmol). In vitro autoradiographic studies of [18F]ICF24027 on different mouse tissue as well as on porcine brain slices demonstrated a moderate specific binding to PDE5. In vivo studies in mice revealed that [18F]ICF24027 was metabolized under formation of brain penetrable radiometabolites making the radiotracer unsuitable for PET imaging of PDE5 in brain. PMID:27110797

  1. New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

    PubMed

    Chen, A C

    2001-10-01

    With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of

  2. Performance Enhancement of the RatCAP Awake Rate Brain PET System

    SciTech Connect

    Vaska, P.; Vaska, P.; Woody, C.; Schlyer, D.; Radeka, V.; O'Connor, P.; Park, S.-J.; Pratte, J.-F.; Junnarkar, M.; Purschke, S.; Southekal, S.; Stoll, S.; Schiffer, W.; Neill, J.; Wharton, D.; Myers, N.; Wiley, S.; Kandasamy, A.; Fried, J.; Krishnamoorthy, S. Kriplani, A.; Maramraju, S.; Lecomte, R.; Fontaine, R.

    2011-03-01

    The first full prototype of the RatCAP PET system, designed to image the brain of a rat while conscious, has been completed. Initial results demonstrated excellent spatial resolution, 1.8 mm FWHM with filtered backprojection and <1.5 mm FWHM with a Monte Carlo based MLEM method. However, noise equivalent countrate studies indicated the need for better timing to mitigate the effect of randoms. Thus, the front-end ASIC has been redesigned to minimize time walk, an accurate coincidence time alignment method has been implemented, and a variance reduction technique for the randoms is being developed. To maximize the quantitative capabilities required for neuroscience, corrections are being implemented and validated for positron range and photon noncollinearity, scatter (including outside the field of view), attenuation, randoms, and detector efficiency (deadtime is negligible). In addition, a more robust and compact PCI-based optical data acquisition system has been built to replace the original VME-based system while retaining the linux-based data processing and image reconstruction codes. Finally, a number of new animal imaging experiments have been carried out to demonstrate the performance of the RatCAP in real imaging situations, including an F-18 fluoride bone scan, a C-11 raclopride scan, and a dynamic C-11 methamphetamine scan.

  3. One-step preparation of [(18)F]FPBM for PET imaging of serotonin transporter (SERT) in the brain.

    PubMed

    Qiao, Hongwen; Zhang, Yan; Wu, Zehui; Zhu, Lin; Choi, Seok Rye; Ploessl, Karl; Kung, Hank F

    2016-08-01

    Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [(18)F]FPBM, 2-(2'-(dimethylamino)methyl)-4'-(3-([(18)F]fluoropropoxy)phenylthio)benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [(18)F]F(-)/K222 to produce [(18)F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [(18)F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [(18)F]FPBM (radiochemical yield, 24-33%, decay corrected; radiochemical purity >99%). PET imaging studies in normal monkeys (n=4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5mg/kg iv injection at 30min after [(18)F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [(18)F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [(18)F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [(18)F]FPBM for in vivo PET imaging of SERT binding in the brain. PMID:27236282

  4. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor

    PubMed Central

    Burns, H. Donald; Van Laere, Koen; Sanabria-Bohórquez, Sandra; Hamill, Terence G.; Bormans, Guy; Eng, Wai-si; Gibson, Ray; Ryan, Christine; Connolly, Brett; Patel, Shil; Krause, Stephen; Vanko, Amy; Van Hecken, Anne; Dupont, Patrick; De Lepeleire, Inge; Rothenberg, Paul; Stoch, S. Aubrey; Cote, Josee; Hagmann, William K.; Jewell, James P.; Lin, Linus S.; Liu, Ping; Goulet, Mark T.; Gottesdiener, Keith; Wagner, John A.; de Hoon, Jan; Mortelmans, Luc; Fong, Tung M.; Hargreaves, Richard J.

    2007-01-01

    [18F]MK-9470 is a selective, high-affinity, inverse agonist (human IC50, 0.7 nM) for the cannabinoid CB1 receptor (CB1R) that has been developed for use in human brain imaging. Autoradiographic studies in rhesus monkey brain showed that [18F]MK-9470 binding is aligned with the reported distribution of CB1 receptors with high specific binding in the cerebral cortex, cerebellum, caudate/putamen, globus pallidus, substantia nigra, and hippocampus. Positron emission tomography (PET) imaging studies in rhesus monkeys showed high brain uptake and a distribution pattern generally consistent with that seen in the autoradiographic studies. Uptake was blocked by pretreatment with a potent CB1 inverse agonist, MK-0364. The ratio of total to nonspecific binding in putamen was 4–5:1, indicative of a strong specific signal that was confirmed to be reversible via displacement studies with MK-0364. Baseline PET imaging studies in human research subject demonstrated behavior of [18F]MK-9470 very similar to that seen in monkeys, with very good test–retest variability (7%). Proof of concept studies in healthy young male human subjects showed that MK-0364, given orally, produced a dose-related reduction in [18F]MK-9470 binding reflecting CB1R receptor occupancy by the drug. Thus, [18F]MK-9470 has the potential to be a valuable, noninvasive research tool for the in vivo study of CB1R biology and pharmacology in a variety of neuropsychiatric disorders in humans. In addition, it allows demonstration of target engagement and noninvasive dose-occupancy studies to aid in dose selection for clinical trials of CB1R inverse agonists. PMID:17535893

  5. MicroPET/CT assessment of FDG uptake in brain after long-term methylphenidate treatment in nonhuman primates.

    PubMed

    Zhang, X; Newport, G D; Callicott, R; Liu, S; Thompson, J; Berridge, M S; Apana, S M; Slikker, W; Wang, C; Paule, M G

    2016-01-01

    Methylphenidate (MPH) is a psychostimulant commonly used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Since the long-term effects of this drug on the central nervous system (CNS) are not well understood, we conducted microPET/CT scans on young adult male rhesus monkeys (n=4/group) to gather information on brain metabolism using the uptake of [(18)F]Fluoro-2-deoxy-2-d-glucose (FDG) as a marker. Approximately two-year old, male rhesus monkeys were treated orally with MPH twice per day, five days per week (M-F) over a 6-year period. Subjects received MPH at either 2.5 or 12.5mg/kg/dose or vehicle (Prang). To minimize the acute effects of MPH on FDG uptake, microPET/CT scans were scheduled on Mondays before their first daily dosing of the week (approximately 68h since their last treatment). FDG (370±8.88MBq) was injected intravenously and 30min later microPET/CT images were obtained over 60min. Radiolabeled tracer accumulation in regions of interest (ROIs) in the prefrontal cortex, temporal cortex, striatum and cerebellum were converted into Standard Uptake Values (SUVs). Compared to the control group, the uptake of FDG in the cerebellum was significantly decreased in both the low and high dose groups. These preliminary data demonstrate that microPET imaging is capable of distinguishing differences in retention of FDG in the brains of NHPs treated chronically with MPH and suggests that this approach may provide a minimally invasive biomarker for exploring the effects of chronic MPH treatment on aspects of brain function. PMID:27307090

  6. Memory deficits due to brain injury: unique PET findings and dream alterations.

    PubMed

    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, (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and (11)C 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

  7. 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

  8. 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. PMID:26844770

  9. 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

  10. Sequential and simultaneous dual-isotope brain SPECT: Comparison with PET for estimation and discrimination tasks in early Parkinson disease

    PubMed Central

    Trott, Cathryn M.; El Fakhri, Georges

    2008-01-01

    Parkinson disease (PD) is the second most frequently occurring cerebral degenerative disease, after Alzheimer disease. Treatments are available, but their efficacy is diminished unless they are administered in the early stages. Therefore, early identification of PD is crucial. In addition to providing perfectly registered studies, simultaneous 99mTc∕123I imaging makes possible the assessment of pre- and postsynaptic neurotransmission functions under identical physiological conditions, while doubling the number of counts for the same total imaging time. These advantages are limited, however, by cross talk between the two radionuclides due to the close emission energies of 99mTc (140 keV) and 123I (159 keV). PET, on the other hand, provides good temporal and spatial resolution and sensitivity but usually requires the use of a single radionuclide. In the present work, the authors compared brain PET with sequential and simultaneous dual-isotope SPECT for the task of estimating striatal activity concentration and striatal size for a normal brain and two stages of early PD. Realistic Monte Carlo simulations of a time-of-flight PET scanner and gamma cameras were performed while modeling all interactions in the brain, collimator (gamma camera) and crystal (detector block in PET), as well as population biological variability of pre- and postsynaptic uptake. For SPECT imaging, we considered two values of system energy resolution and scanners with two and three camera heads. The authors used the Cramer–Rao bound, as a surrogate for the best theoretical performance, to optimize the SPECT acquisition energy windows and objectively compare PET and SPECT. The authors determined the discrimination performance between 500 simulated subjects in every disease stage as measured by the area under the ROC curve (AUC). The discrimination accuracy between a normal subject and a subject in the prodromal disease stage was AUC=0.924 with PET, compared to 0.863 and 0.831 with simultaneous

  11. Synthesis and bioimaging of positron-emitting 15O-labeled 2-deoxy-D-glucose of two-minute half-life.

    PubMed

    Yorimitsu, Hideki; Murakami, Yoshihiro; Takamatsu, Hiroyuki; Nishimura, Shintaro; Nakamura, Eiichi

    2007-01-01

    In positron emission tomography (PET), which exploits the affinity of a radiopharmaceutical for the target organ, a systematic repertoire of oxygen-15-labeled PET tracers is expected to be useful for bioimaging owing to the ubiquity of oxygen atoms in organic compounds. However, because of the 2-min half-life of 15O, the synthesis of complex biologically active 15O-labeled organic molecules has not yet been achieved. A state-of-the-art synthesis now makes available an 15O-labeled complex organic molecule, 6-[15O]-2-deoxy-D-glucose. Ultrarapid radical hydroxylation of 2,6-dideoxy-6-iodo-D-glucose with molecular oxygen labeled with 15O of two-minute half-life provided the target 15O-labeled molecule. The labeling reaction with 15O was complete in 1.3 min, and the entire operation time starting from the generation of 15O-containing dioxygen by a cyclotron to the purification of the labeled sugar was 7 min. The labeled sugar accumulated in the metabolically active organs as well as in the bladder of mice and rats. 15O-labeling offers the possibility of repetitive scanning and the use of multiple PET tracers in the same body within a short time, and hence should significantly expand the scope of PET studies of small animals. PMID:17441139

  12. Advancing PET science for new measures of brain function. Progress report, January 1, 1994--December 31, 1994

    SciTech Connect

    Kuhl, D.E.

    1994-10-01

    This project has continued the development of new chemistry and imaging physics applicable to PET studies of the human brain. In basic radiochemistry research, the authors have developed a modified approach to solid-phase supported [{sup 11}C]methylation system, in part dependent on the design, fabrication and validation of new small, sensitive and accurate positron detectors useful in tracking the flow of radioactivity through the synthesis apparatus. Radiopharmaceutical efforts have resulted in synthesis of new tracers of mitochondrial enzymes. For evaluation of new PET radiotracers, the authors have applied new models of unilateral brain lesions using quinolinic acid and MPP+, as models of neurodegenerative diseases. In the physics and data analysis research area the authors have developed faster and more accurate means of performing image reconstruction for use with both emission and transmission data. The authors are optimizing acquisition and kinetic modeling strategies for new radiotracers. The authors also have implemented and proven the utility of performing task switching during PET CBF activation studies for the purpose of enhancing signal-to-noise and greater detectability of areas of activation. The authors also working on routines for standardization of analysis strategies for group vs. group and individual vs. group comparisons.

  13. Candidate PET Radioligand Development for Neurofibrillary Tangles: Two Distinct Radioligand Binding Sites Identified in Postmortem Alzheimer's Disease Brain.

    PubMed

    Cai, Lisheng; Qu, Baoxi; Hurtle, Bryan T; Dadiboyena, Sureshbabu; Diaz-Arrastia, Ramon; Pike, Victor W

    2016-07-20

    [(18)F]THK-523 and [(18)F]807 are promising radioligands for imaging neurofibrillary tangles (NFTs) with positron emission tomography (PET) in neurodegenerative diseases, such as Alzheimer's disease (AD) and traumatic brain injury. Although [(18)F]THK-523 and [(18)F]T807 are considered high-affinity selective radioligands for NFTs, uncertainty has existed as to whether PET radioligands for imaging NFTs bind to the same molecular site because in vitro assays for ligands binding to NFTs have been lacking. We labeled THK-523 and T807 with tritium to serve as reference radioligands for in vitro binding assays with AD brain homogenates for newly synthesized ligands. With these radioligands, we identified two distinct binding sites for small molecules, one site with high affinity for THK-523 and the other with high affinity for T807. Moreover, binding assays with [(3)H]PIB confirmed that the two newly identified binding sites are also distinct from the thioflavin-T binding site where all current clinically useful PET radioligands for imaging β-amyloid plaque bind with high affinity. The two newly identified binding sites are considered to reside on NFTs rather than on β-amyloid plaques. Furthermore, we applied all three binding assays to a set of newly prepared compounds, based on chain modifications to THK-523. Some compounds with high affinity and selectivity for the THK-523 binding site emerged from this set, including one with amenability to labeling with fluorine-18, namely, ligand 10b. PMID:27171905

  14. 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

  15. 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

  16. Predicting conversion from MCI to AD with FDG-PET brain images at different prodromal stages.

    PubMed

    Cabral, Carlos; Morgado, Pedro M; Campos Costa, Durval; Silveira, Margarida

    2015-03-01

    Early diagnosis of Alzheimer disease (AD), while still at the stage known as mild cognitive impairment (MCI), is important for the development of new treatments. However, brain degeneration in MCI evolves with time and differs from patient to patient, making early diagnosis a very challenging task. Despite these difficulties, many machine learning techniques have already been used for the diagnosis of MCI and for predicting MCI to AD conversion, but the MCI group used in previous works is usually very heterogeneous containing subjects at different stages. The goal of this paper is to investigate how the disease stage impacts on the ability of machine learning methodologies to predict conversion. After identifying the converters and estimating the time of conversion (TC) (using neuropsychological test scores), we devised 5 subgroups of MCI converters (MCI-C) based on their temporal distance to the conversion instant (0, 6, 12, 18 and 24 months before conversion). Next, we used the FDG-PET images of these subgroups and trained classifiers to distinguish between the MCI-C at different stages and stable non-converters (MCI-NC). Our results show that MCI to AD conversion can be predicted as early as 24 months prior to conversion and that the discriminative power of the machine learning methods decreases with the increasing temporal distance to the TC, as expected. These findings were consistent for all the tested classifiers. Our results also show that this decrease arises from a reduction in the information contained in the regions used for classification and by a decrease in the stability of the automatic selection procedure. PMID:25625698

  17. Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine

    SciTech Connect

    Wienhard, K.; Herholz, K.; Coenen, H.H.; Rudolf, J.; Kling, P.; Stoecklin, G.H.; Heiss, W.D. )

    1991-07-01

    The uptake of L-(2-18F)fluorotyrosine (F-Tyr), a newly synthetized amino acid tracer, was studied in 15 patients with various brain tumors by dynamic PET. The higher F-Tyr accumulation in tumors (mean 27% above contralateral tissue) was associated with two-fold transport rates into tumors, while the rate constants describing irreversible incorporation were decreased. The increased F-Tyr transport was not correlated to 68Ga-EDTA accumulation and cannot be explained by disruption of the blood-brain barrier. Kinetic analysis of 2-(18F)-fluoro-deoxy-glucose accumulation in the same patients demonstrated that increased metabolic rates in tumors are mainly caused by altered phosphorylation rates while transport of glucose is less affected. Since F-Tyr transport rates clearly separated tumors from normal tissue and since F-Tyr accumulation was related to tumor grade, PET studies of F-Tyr uptake are of clinical value for diagnosis and classification of brain tumors.

  18. Conflict Processing in the Rat Brain: Behavioral Analysis and Functional μPET Imaging Using [18F]Fluorodeoxyglucose

    PubMed Central

    Marx, Christine; Lex, Björn; Calaminus, Carsten; Hauber, Wolfgang; Backes, Heiko; Neumaier, Bernd; Mies, Günter; Graf, Rudolf; Endepols, Heike

    2012-01-01

    Conflicts in spatial stimulus–response tasks occur when the task-relevant feature of a stimulus implies a response toward a certain location which does not match the location of stimulus presentation. This conflict leads to increased error rates and longer reaction times, which has been termed Simon effect. A model of dual route processing (automatic and intentional) of stimulus features has been proposed, predicting response conflicts if the two routes are incongruent. Although there is evidence that the prefrontal cortex, notably the anterior cingulate cortex (ACC), plays a crucial role in conflict processing, the neuronal basis of dual route architecture is still unknown. In this study, we pursue a novel approach using positron emission tomography (PET) to identify relevant brain areas in a rat model of an auditory Simon task, a neuropsychological interference task, which is commonly used to study conflict processing in humans. For combination with PET we used the metabolic tracer [18F]fluorodeoxyglucose, which accumulates in metabolically active brain cells during the behavioral task. Brain areas involved in conflict processing are supposed to be activated when automatic and intentional route processing lead to different responses (dual route model). Analysis of PET data revealed specific activation patterns for different task settings applicable to the dual route model as established for response conflict processing. The rat motor cortex (M1) may be part of the automatic route or involved in its facilitation, while premotor (M2), prelimbic, and ACC seemed to be essential for inhibiting the incorrect, automatic response, indicating conflict monitoring functions. Our findings and the remarkable similarities to the pattern of activated regions reported during conflict processing in humans demonstrate that our rodent model opens novel opportunities to investigate the anatomical basis of conflict processing and dual route architecture. PMID:22363272

  19. Using PET H2O15 brain imaging to study the functional-anatomical correlates of non-human primate communication.

    PubMed

    Gil-da-Costa, Ricardo; Braun, Allen; Martin, Alex

    2006-03-01

    In this article, we describe methods for using oxygen-15 water (H2O15) positron emission tomography (PET) to explore the functional neuroanatomy of cognition in awake, non-human primates. The discussion is based on a recent study designed to identify regions in the monkey brain associated with perceiving auditory stimuli, and species-specific calls, in particular [Gil-da-Costa et al., Proc. Natl. Acad. Sci. USA 101 (2004) 17516-17521]. Details are provided concerning critical aspects of the experimental paradigm, including pre-scanning habituation sessions to acclimate the animals to the PET scanner environment, and details of a pilot study to determine the auditory stimulus parameters necessary to produce robust activity in brain regions known to process auditory information (belt and parabelt regions of monkey auditory cortex). Methods for acquiring and analyzing PET data to identify significant regions of brain activity in single animals are also presented. PMID:16466931

  20. 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.

  1. PET measurement of C-11-methylphenidate pharmacokinetics and distribution in the human brain

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Wang, G.J.

    1994-05-01

    Methylphenidate (MP), a psychostimulant drug which binds to the dopamine transporter (DAT), is the most commonly prescribed psychotropic medication for children in the USA yet little is known about its pharmacokinetics and distribution in the human brain. PET was used to measure the pharmacokinetics of d,l-threo-[{sup 11}C]methylphenidate (MP*) the labelled form of the prescribed drug (ritalin) in eight normal male subjects (age range 20-74 years). Four subjects had 2 repeated scans to assess test/retest reproducibility and 4 had one wan as baseline and the second 10 minutes after administration of 0.5 mg/kg MP to assess specific to nonspecific binding. Dynamic scans were started immediately after injection of MP*(5-10 mCi) for 90 min on the CTI-931 (6 x 6 x 6.5 mm FWHM). Time activity curves for tissue concentration and for unchanged tracer in plasma were used to calculate the distribution volume (DV) in basal ganglia (BG), cerebellum (CB) and global (GL) regions using graphical analysis. Binding of MP* was highest in the BG (0.008% dose/cc) uptake in CB corresponded to (0.006) and in GL to (0.005). Kinetic analysis revealed fast uptake of MP* with peak uptake in BG occurring 5-20 min PI, and in CB and GL at 5-13 min PI. Half time clearance for MP* occurred 90 min PI for BG and 60 min for CB and GL. Test/retest variability was <10% (range -0.5 to +7.0% for the DV ratio (BG/CB)). Pretreatment with MP selectively reduced uptake in BG wherein it did not affect uptake in CB or GL. The ratio of the DV in BG to that in CB changed from 2.12{plus_minus}0.1 to 1.35{plus_minus}0.04. The lack of an effect of MP in CB an area with a high density of norepinephrine (NE) transporters suggests that MP* is not binding to the NE transporter.

  2. 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

  3. Bevacizumab Targeting Diffuse Intrinsic Pontine Glioma: Results of 89Zr-Bevacizumab PET Imaging in Brain Tumor Models.

    PubMed

    Jansen, Marc H A; Lagerweij, Tonny; Sewing, A Charlotte P; Vugts, Danielle J; van Vuurden, Dannis G; Molthoff, Carla F M; Caretti, Viola; Veringa, Susanna J E; Petersen, Naomi; Carcaboso, Angel M; Noske, David P; Vandertop, W Peter; Wesseling, Pieter; van Dongen, Guus A M S; Kaspers, Gertjan J L; Hulleman, Esther

    2016-09-01

    The role of the VEGF inhibitor bevacizumab in the treatment of diffuse intrinsic pontine glioma (DIPG) is unclear. We aim to study the biodistribution and uptake of zirconium-89 ((89)Zr)-labeled bevacizumab in DIPG mouse models. Human E98-FM, U251-FM glioma cells, and HSJD-DIPG-007-FLUC primary DIPG cells were injected into the subcutis, pons, or striatum of nude mice. Tumor growth was monitored by bioluminescence imaging (BLI) and visualized by MRI. Seventy-two to 96 hours after (89)Zr-bevacizumab injections, mice were imaged by positron emission tomography (PET), and biodistribution was analyzed ex vivo High VEGF expression in human DIPG was confirmed in a publically available mRNA database, but no significant (89)Zr-bevacizumab uptake could be detected in xenografts located in the pons and striatum at an early or late stage of the disease. E98-FM, and to a lesser extent the U251-FM and HSJD-DIPG-007 subcutaneous tumors, showed high accumulation of (89)Zr-bevacizumab. VEGF expression could not be demonstrated in the intracranial tumors by in situ hybridization (ISH) but was clearly present in the perinecrotic regions of subcutaneous E98-FM tumors. The poor uptake of (89)Zr-bevacizumab in xenografts located in the brain suggests that VEGF targeting with bevacizumab has limited efficacy for diffuse infiltrative parts of glial brain tumors in mice. Translating these results to the clinic would imply that treatment with bevacizumab in patients with DIPG is only justified after targeting of VEGF has been demonstrated by (89)Zr-bevacizumab immuno-PET. We aim to confirm this observation in a clinical PET study with patients with DIPG. Mol Cancer Ther; 15(9); 2166-74. ©2016 AACR. PMID:27325687

  4. Quantitative characterization of brain β-amyloid using a joint PiB/FDG PET image histogram

    NASA Astrophysics Data System (ADS)

    Camp, Jon J.; Hanson, Dennis P.; Holmes, David R.; Kemp, Bradley J.; Senjem, Matthew L.; Murray, Melissa E.; Dickson, Dennis W.; Parisi, Joseph; Petersen, Ronald C.; Lowe, Val J.; Robb, Richard A.

    2014-03-01

    A complex analysis performed by spatial registration of PiB and MRI patient images in order to localize the PiB signal to specific cortical brain regions has been proven effective in identifying imaging characteristics associated with underlying Alzheimer's Disease (AD) and Lewy Body Disease (LBD) pathology. This paper presents an original method of image analysis and stratification of amyloid-related brain disease based on the global spatial correlation of PiB PET images with 18F-FDG PET images (without MR images) to categorize the PiB signal arising from the cortex. Rigid registration of PiB and 18F-FDG images is relatively straightforward, and in registration the 18F-FDG signal serves to identify the cortical region in which the PiB signal is relevant. Cortical grey matter demonstrates the highest levels of amyloid accumulation and therefore the greatest PiB signal related to amyloid pathology. The highest intensity voxels in the 18F-FDG image are attributed to the cortical grey matter. The correlation of the highest intensity PiB voxels with the highest 18F-FDG values indicates the presence of β-amyloid protein in the cortex in disease states, while correlation of the highest intensity PiB voxels with mid-range 18F-FDG values indicates only nonspecific binding in the white matter.

  5. Assessment of Traumatic Brain Injury by Increased 64Cu Uptake on 64CuCl2 PET/CT

    PubMed Central

    Peng, Fangyu; Muzik, Otto; Gatson, Joshua; Kernie, Steven G.; Diaz-Arrastia, Ramon

    2015-01-01

    Copper is a nutritional trace element required for cell proliferation and wound repair. Methods To explore increased copper uptake as a biomarker for noninvasive assessment of traumatic brain injury (TBI), experimental TBI in C57BL/6 mice was induced by controlled cortical impact, and 64Cu uptake in the injured cortex was assessed with 64CuCl2 PET/CT. Results At 24 h after intravenous injection of the tracer, uptake was significantly higher in the injured cortex of TBI mice (1.15 ± 0.53 percentage injected dose per gram of tissue [%ID/g]) than in the uninjured cortex of mice without TBI (0.53 ± 0.07 %ID/g, P = 0.027) or the cortex of mice that received an intracortical injection of zymosan A (0.62 ± 0.22 %ID/g, P = 0.025). Furthermore, uptake in the traumatized cortex of untreated TBI mice (1.15 ± 0.53 %ID/g) did not significantly differ from that in minocycline-treated TBI mice (0.93 ± 0.30 %ID/g, P = 0.33). Conclusion Overall, the data suggest that increased 64Cu uptake in traumatized brain tissues holds potential as a new biomarker for noninvasive assessment of TBI with 64CuCl2 PET/CT. PMID:26112025

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

    SciTech Connect

    Mathias, C.J.; Welch, M.J.; Raichle, M.E.; Mintun, M.A.; Lich, L.L.; McGuire, A.H.; Zinn, K.R.; John, E.K.; Green, M.A. )

    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 and 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.

  7. [German Society of Nuclear Medicine procedure guideline on beta-amyloid brain PET imaging].

    PubMed

    Barthel, Henryk; Meyer, Philipp T; Drzezga, Alexander; Bartenstein, Peter; Boecker, Henning; Brust, Peter; Buchert, Ralph; Coenen, Heinz H; la Fougère, Christian; Gründer, Gerhard; Grünwald, Frank; Krause, Bernd J; Kuwert, Torsten; Schreckenberger, Matthias; Tatsch, Klaus; Langen, Karl-Josef; Sabri, Osama

    2016-08-01

    Recently, a number of positron emission tomography (PET) radiotracers have been approved for clinical use. These tracers target cerebral beta-amyloid (Aβ) plaques, a hallmark of Alzheimer's disease. Increasing use of this method implies the need for respective standards. This German Society of Nuclear Medicine guideline describes adequate procedures for Aβ plaque PET imaging. It not only discusses the tracers used for that purpose, but also lists measures for correct patient preparation, image data generation, processing, analysis and interpretation. With that, this "S1" category (according to the German Association of the Scientific Medical Societies standard) guideline aims at contributing to quality assurance of nuclear imaging in Germany. PMID:27080914

  8. ROC (Receiver Operating Characteristics) study of maximum likelihood estimator human brain image reconstructions in PET (Positron Emission Tomography) clinical practice

    SciTech Connect

    Llacer, J.; Veklerov, E.; Nolan, D. ); Grafton, S.T.; Mazziotta, J.C.; Hawkins, R.A.; Hoh, C.K.; Hoffman, E.J. )

    1990-10-01

    This paper will report on the progress to date in carrying out Receiver Operating Characteristics (ROC) studies comparing Maximum Likelihood Estimator (MLE) and Filtered Backprojection (FBP) reconstructions of normal and abnormal human brain PET data in a clinical setting. A previous statistical study of reconstructions of the Hoffman brain phantom with real data indicated that the pixel-to-pixel standard deviation in feasible MLE images is approximately proportional to the square root of the number of counts in a region, as opposed to a standard deviation which is high and largely independent of the number of counts in FBP. A preliminary ROC study carried out with 10 non-medical observers performing a relatively simple detectability task indicates that, for the majority of observers, lower standard deviation translates itself into a statistically significant detectability advantage in MLE reconstructions. The initial results of ongoing tests with four experienced neurologists/nuclear medicine physicians are presented. Normal cases of {sup 18}F -- fluorodeoxyglucose (FDG) cerebral metabolism studies and abnormal cases in which a variety of lesions have been introduced into normal data sets have been evaluated. We report on the results of reading the reconstructions of 90 data sets, each corresponding to a single brain slice. It has become apparent that the design of the study based on reading single brain slices is too insensitive and we propose a variation based on reading three consecutive slices at a time, rating only the center slice. 9 refs., 2 figs., 1 tab.

  9. FDG-PET in the selection of brain lesions for biopsy

    SciTech Connect

    Hanson, M.W.; Glantz, M.J.; Hoffman, J.M.; Friedman, A.H.; Burger, P.C.; Schold, S.C.; Coleman, R.E. )

    1991-09-01

    The CT-guided stereotaxic needle biopsy has become a widely used procedure in the diagnostic evaluation of intracranial lesions including tumors. Conventional CT or MR frequently defines the anatomic regions of abnormality, which may be multiple lesions or a single lesion that is heterogeneous in cellular composition owing to the topographic variation of cellular constituency or the combination of active disease, nonspecific inflammation, necrosis, and/or edema. In these cases, selection of the most appropriate site for a successful diagnostic needle biopsy can be difficult. In three patients, we have used (18F)fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the site most likely to provide a diagnostic biopsy result. In the first patient, who presented with confusion, multiple biopsies from the temporal lobe, based on MR abnormalities, revealed only reactive gliosis and edema. Repeat biopsy directed by PET revealed an anaplastic astrocytoma. In a second patient, PET allowed us to differentiate radiation effect from active metastatic breast cancer. In the third patient, who presented with a grand mal seizure, biopsy of a CT-defined hypodense region demonstrated lymphocytosis. Metabolism of FDG was normal or increased in areas of Aspergillus encephalitis at autopsy. These preliminary studies suggest a complementary role for FDG-PET and CT or MR in selected patients for defining the intracranial site most likely to yield a positive biopsy result.

  10. Comparative evaluation of 18F-FDOPA, 13N-AMMONIA, 18F-FDG PET/CT and MRI in primary brain tumors - A pilot study

    PubMed Central

    Jora, Charu; Mattakarottu, Jacob J; Aniruddha, Pandit G; Mudalsha, Ravina; Singh, Dhananjay K; Pathak, Harish C; Sharma, Nitin; Sarin, Arti; Prince, Arvind; Singh, Giriraj

    2011-01-01

    Aim: To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and 18F-FDG PET/CT in primary brain tumors and comparison with magnetic resonance imaging (MRI). Materials and Methods: A total of 23 patients, 8 preoperative and 15 postoperative, undergoing evaluation for primary brain tumors were included in this study. Of them, 9/15 were operated for high grade gliomas (7/9 astrocytomas and 2/9 oligodendrogliomas) and 6/15 for low grade gliomas (5/6 astrocytomas and 1/6 oligodendroglioma). After PET study, 2 of 8 preoperative cases were histopathologically proven to be of benign etiology. 3 low grade and 2 high grade postoperative cases were disease free on 6 months follow-up. Tracer uptake was quantified by standardized uptake values (SUVmax) and the SUV max ratio of tumor to normal symmetrical area of contra lateral hemisphere (T/N). 18F-FDOPA uptake was also quantified by SUVmax ratio of tumor to striatum (T/S). Conventional MR studies were done in all patients. Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA PET. Sensitivity of 18F-FDOPA PET was substantially higher (6/6 preoperative, 3/3 low grade postoperative, 7/7 high grade postoperative) than with 18F-FDG (3/6 preoperative, 1/3 low grade postoperative, 3/7 high grade postoperative) and 13N-Ammonia PET (2/6 preoperative, 1/3 low grade postoperative, 1/7 high grade postoperative). FDOPA was equally specific as FDG and Ammonia PET in operated cases but was falsely positive in two preoperative cases. Sensitivity of FDOPA (16/16) was more than MRI (13/16). Conclusion: 18F-FDG uptake correlates with tumor grade. Though 18F-FDOPA PET cannot distinguish between tumor grade, it is more reliable than 18F-FDG and 13N-Ammonia PET for evaluating brain tumors. 18F-FDOPA PET may prove to be superior to MRI in evaluating recurrence and residual tumor tissue. 13N-Ammonia PET did not show any encouraging results. PMID:22174511

  11. Regional brain distribution of 2-deoxy-2-[F-18]Fluoro-D-talose: A new PET tracer for measurement of galactokinase activity

    SciTech Connect

    Haradahira, T.; Inoue, O.; Suzuki, K.

    1994-05-01

    We have recently developed a 2-deoxy-2-[F-18]fluoro-D-talose (2-[F-18]FDTal) as a new PET tracer for measurements of galactokinase activities in tissues. The rational of 2-[F-18]FDTal as a PET tracer is based on the metabolic trapping by a formation of 2-[F-18]FDTal-1-phosphate by galactokinase. In this study, we have examined the regional brain distribution of 2-[F-18]FDTal in monkey by PET, and compared it with those of 2-deoxy-2-[F-18]fluoro-D-glucose (2-[F-18]FDG) and 2-deoxy-2-[F-18]fluoro-D-galactose (2-[F-18]FDTal), PET tracers for D-glucose and D-galactose metabolisms, respectively. The F-18 sugars used for the PET studies were prepared through nucleophilic fluorinations of the corresponding triflates with [F-18]fluoride. PET imaging obtained by i.v. injection of 2-[F-18]FDTal in rhesus monkey showed very high accumulation of the radioactivity into an occipital cortex region. This regional distribution was very similar to that of 2-[F-18]FDGal, but was quite different with that of 2-[F-18]FDG. In PET data analyses, washout of the radioactivity from the occipital cortex (30% loss of the initial activity) was observed in an early period ({<=}5 min) after injection of 2-[F-18]FDTal, in contrast with the continuous increase of the radioactivity in the same region after injection of 2-[F-18]FDGal. This data indicates a smaller phosphorylation rate constant (K3) of 2-[F-18]FDTal by brain galactokinase than that of 2-[F-18]FDGal. 2-[F-18]FDGal has been reported to be partly metabolized into an UDP-2-[F-18]FDGal via 2-CF-18]FDGal-l-phosphate in animal brains. Therefore 2-[F-18]FDTal offers an advantage over 2-[F-18]FDGal in undergoing its simple metabolism which enables us to make a simple kinetic model for PET imaging. We conclude that 2-[F-18]FDTal may be a new PET tracer to give a characteristic regional brain distribution which reflect the regional galactokinase activity.

  12. Positron range estimations with PeneloPET

    NASA Astrophysics Data System (ADS)

    Cal-González, J.; Herraiz, J. L.; España, S.; Corzo, P. M. G.; Vaquero, J. J.; Desco, M.; Udias, J. M.

    2013-08-01

    Technical advances towards high resolution PET imaging try to overcome the inherent physical limitations to spatial resolution. Positrons travel in tissue until they annihilate into the two gamma photons detected. This range is the main detector-independent contribution to PET imaging blurring. To a large extent, it can be remedied during image reconstruction if accurate estimates of positron range are available. However, the existing estimates differ, and the comparison with the scarce experimental data available is not conclusive. In this work we present positron annihilation distributions obtained from Monte Carlo simulations with the PeneloPET simulation toolkit, for several common PET isotopes (18F, 11C, 13N, 15O, 68Ga and 82Rb) in different biological media (cortical bone, soft bone, skin, muscle striated, brain, water, adipose tissue and lung). We compare PeneloPET simulations against experimental data and other simulation results available in the literature. To this end the different positron range representations employed in the literature are related to each other by means of a new parameterization for positron range profiles. Our results are generally consistent with experiments and with most simulations previously reported with differences of less than 20% in the mean and maximum range values. From these results, we conclude that better experimental measurements are needed, especially to disentangle the effect of positronium formation in positron range. Finally, with the aid of PeneloPET, we confirm that scaling approaches can be used to obtain universal, material and isotope independent, positron range profiles, which would considerably simplify range correction.

  13. [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain.

    PubMed

    Visser, Anniek K D; Ramakrishnan, Nisha K; Willemsen, Antoon T M; Di Gialleonardo, Valentina; de Vries, Erik F J; Kema, Ido P; Dierckx, Rudi A J O; van Waarde, Aren

    2014-01-01

    The PET tracer [(11)C]5-hydroxytryptophan ([(11)C]5-HTP), which is converted to [(11)C]5-hydroxytryptamine ([(11)C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [(11)C]5-HTP in rat? Male rats were scanned with [(11)C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [(11)C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [(11)C]5-HTP uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme converting [(11)C]5-HTP to [(11)C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [(11)C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents. PMID:24084697

  14. 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. PMID:26497357

  15. What approach to brain partial volume correction is best for PET/MRI?

    NASA Astrophysics Data System (ADS)

    Hutton, B. F.; Thomas, B. A.; Erlandsson, K.; Bousse, A.; Reilhac-Laborde, A.; Kazantsev, D.; Pedemonte, S.; Vunckx, K.; Arridge, S. R.; Ourselin, S.

    2013-02-01

    Many partial volume correction approaches make use of anatomical information, readily available in PET/MRI systems but it is not clear what approach is best. Seven novel approaches to partial volume correction were evaluated, including several post-reconstruction methods and several reconstruction methods that incorporate anatomical information. These were compared with an MRI-independent approach (reblurred van Cittert ) and uncorrected data. Monte Carlo PET data were generated for activity distributions representing both 18F FDG and amyloid tracer uptake. Post-reconstruction methods provided the best recovery with ideal segmentation but were particularly sensitive to mis-registration. Alternative approaches performed better in maintaining lesion contrast (unseen in MRI) with good noise control. These were also relatively insensitive to mis-registration errors. The choice of method will depend on the specific application and reliability of segmentation and registration algorithms.

  16. Sequential [(18)F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity.

    PubMed

    Zwergal, Andreas; Schlichtiger, Julia; Xiong, Guoming; Beck, Roswitha; Günther, Lisa; Schniepp, Roman; Schöberl, Florian; Jahn, Klaus; Brandt, Thomas; Strupp, Michael; Bartenstein, Peter; Dieterich, Marianne; Dutia, Mayank B; la Fougère, Christian

    2016-01-01

    Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery. PMID:25269833

  17. Coincidental Observation of Global Hypometabolism in the Brain on PET/CT of an AIDS Patient With High-Grade Pulmonary Non-Hodgkin Lymphoma.

    PubMed

    Chandra, Piyush; Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2016-08-01

    AIDS-related dementia complex is the most severe form of cognitive dysfunction in a patient infected with human immunodeficiency virus. The use of FDG PET/CT to diagnose AIDS-related dementia complex has been studied previously and shows various specific metabolic patterns from striatal hypermetabolism in early asymptomatic stage to global hypometabolism in advanced stages. We present a case of a 49-year-old patient with long-standing human immunodeficiency virus infection, where global brain hypometabolism was noted coincidentally on FDG PET/CT done for initial staging of primary pulmonary non-Hodgkin lymphoma. PMID:27280906

  18. SU-D-9A-04: Brain PET/CT Imaging On a Scanner with a Large Axial Field-Of-View

    SciTech Connect

    Park, M; Gerbaudo, V; Hamberg, L; Seaver, K; Kijewski, M

    2014-06-01

    Purpose: Large axial field-of-view (FOV) PET/CT scanners are valued for high sensitivity. Brain PET image quality may depend on the head position within the FOV. We investigated the precision of activity estimation for brain PET imaging when the brain was positioned at the end (END) and in the middle (CEN) of the FOV. The additional CT dose for the CEN position was recorded. Methods: An image quality (Jaszczak) phantom and a striatal phantom were filled with F-18 and positioned in END and CEN locations. For each phantom and each location, we acquired a ∼1-hr listmode PET, rebinned the data into 10 frames with equal number of coincidence events, and reconstructed each frame using an iterative algorithm. For the striatal phantom, END and CEN were compared by drawing on each image three regions of interest (ROI) in axially separated uniform areas. The standard deviation of the activity estimation within each ROI was averaged over the 10 images. The coefficient of variation (CV) for activity estimation was calculated at each position. Image quality was assessed by inspecting the resolution bar pattern in the Jaszczak phantom at two different head positions. Results: The CV was the lowest for ROIs near the center of the FOV. For slices near the end, not only was the CV highest, but also the resolution pattern was degraded. CTDIvol summarized in the dose report indicated that the CT dose was ∼ 10% higher for CEN as compared to END position. Conclusion: Positioning the brain in the middle of the FOV in a large FOV PET/CT scanner allows more precise measurement of tracer uptake and better image quality at the cost of increased CT dose. For the end location longer scan times may minimize image quality degradation without any additional CT dose.

  19. Large Variation in Brain Exposure of Reference CNS Drugs: a PET Study in Nonhuman Primates

    PubMed Central

    Varnäs, Katarina; Lundquist, Stefan; Nakao, Ryuji; Amini, Nahid; Takano, Akihiro; Finnema, Sjoerd J.; Halldin, Christer; Farde, Lars

    2015-01-01

    Background: Positron emission tomography microdosing of radiolabeled drugs allows for noninvasive studies of organ exposure in vivo. The aim of the present study was to examine and compare the brain exposure of 12 commercially available CNS drugs and one non-CNS drug. Methods: The drugs were radiolabeled with 11C (t 1/2 = 20.4 minutes) and examined using a high resolution research tomograph. In cynomolgus monkeys, each drug was examined twice. In rhesus monkeys, a first positron emission tomography microdosing measurement was repeated after preadministration with unlabeled drug to examine potential dose-dependent effects on brain exposure. Partition coefficients between brain and plasma (K P) were calculated by dividing the AUC0-90 min for brain with that for plasma or by a compartmental analysis (V T). Unbound K P (K P u,u) was obtained by correction for the free fraction in brain and plasma. Results: After intravenous injection, the maximum radioactivity concentration (C max, %ID) in brain ranged from 0.01% to 6.2%. For 10 of the 12 CNS drugs, C max, %ID was >2%, indicating a preferential distribution to brain. A lower C max, %ID was observed for morphine, sulpiride, and verapamil. K P ranged from 0.002 (sulpiride) to 68 (sertraline) and 7 of 13 drugs had K P u,u close to unity. For morphine, sulpiride, and verapamil, K P u,u was <0.3, indicating impaired diffusion and/or active efflux. Brain exposure at microdosing agreed with pharmacological dosing conditions for the investigated drugs. Conclusions: This study represents the largest positron emission tomography study on brain exposure of commercially available CNS drugs in nonhuman primates and may guide interpretation of positron emission tomography microdosing data for novel drug candidates. PMID:25813017

  20. Possible role of an error detection mechanism in brain processing of deception: PET-fMRI study.

    PubMed

    Kireev, Maxim; Korotkov, Alexander; Medvedeva, Natalia; Medvedev, Svyatoslav

    2013-12-01

    To investigate brain maintenance of deliberate deception the positron emission tomography and the event related functional MRI studies were performed. We used an experimental paradigm that presupposed free choices between equally beneficial deceptive or honest actions. Experimental task simulated the "Cheat" card game which aims to defeat an opponent by sequential deceptive and honest claims. Results of both the PET and the fMRI studies revealed that execution of both deliberately deceptive and honest claims is associated with fronto-parietal brain network comprised of inferior and middle frontal gyri, precentral gyrus (BA 6), caudate nucleus, and inferior parietal lobule. Direct comparison between those claims, balanced in terms of decision making and action outcome (gain and losses), revealed activation of areas specifically associated with deception execution: precentral gyrus (BA 6), caudate nuclei, thalamus and inferior parietal lobule (BA 39/40). The obtained experimental data were discussed in relation to a possible role of an error detection system in processing deliberate deception. PMID:24100194

  1. Compartment modeling anslysis of C-11 flumazenil kinetics in human brain using dynamic 2D and 3D PET

    SciTech Connect

    Choi, Y.; Simpson, N.; Townsend, D.W.

    1994-05-01

    We examined the feasibility of compartment modeling analysis and the numerical accuracy of model parameters of radioligand delivery and binding in the brain using 2D and 3D PET. Two subjects were injected with C-11 flumazenil (FMZ) i.v., and imaged over the brain with a dynamic sequence of 6x20 s, 2x30 s, 4x90 s, 4x180 s, 2x300 s, 2x600 s, and 2x1200 s frames. Different scatter correction methods were applied to the 3D data: No scatter correction (NOC), dual-energy window subtraction (DEW) and convolution-subtraction (CON). The kinetic data for regions listed below were fitted to a 2-compartment, 2-parameter model. Both 2D and 3D results are similar and within the expected range. The 3D %SE was less than 2D despite the smaller dose. The effect of the scatter in 3D parameter estimates appears to be small. These preliminary data indicate temporally sufficient kinetic data can be acquired in 3D mode to perform compartmental analysis of C-11 FMZ. Improved sensitivity in 3D may allow more accurate receptor characterization especially in small structures or in low specific binding areas.

  2. Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine): a PET-FDG study

    SciTech Connect

    Brunetti, A.; Berg, G.; Di Chiro, G.; Cohen, R.M.; Yarchoan, R.; Pizzo, P.A.; Broder, S.; Eddy, J.; Fulham, M.J.; Finn, R.D.

    1989-05-01

    Brain glucose metabolism was evaluated in four patients with acquired immunodeficiency syndrome (AIDS) dementia complex using (/sup 18/F)fluorodeoxyglucose (FDG) and positron emission tomography (PET) scans at the beginning of therapy with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine), and later in the course of therapy. In two patients, baseline, large focal cortical abnormalities of glucose utilization were reversed during the course of therapy. In the other two patients, the initial PET study did not reveal pronounced focal alterations, while the post-treatment scans showed markedly increased cortical glucose metabolism. The improved cortical glucose utilization was accompanied in all patients by immunologic and neurologic improvement. PET-FDG studies can detect cortical metabolic abnormalities associated with AIDS dementia complex, and may be used to monitor the metabolic improvement in response to AZT treatment.

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

    PubMed

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

    2016-08-01

    Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with [Formula: see text] (15)O or C(15)O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic [Formula: see text] (15)O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  <8% and the calculated CBF values showed a tight correlation (r  =  0.97). The simulation showed that errors associated with the assumed parameters were  <10%, and that the optimal number of tissue curves to be used was around 500. Our results demonstrate that IDIF can be reconstructed directly from tissue curves obtained through [Formula: see text] (15)O PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies. PMID:27401833

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

    The human brain exhibits marked hemispheric differences, though it is not fully understood to what extent lateralization of the epileptic focus is relevant. Preoperative [18F]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 [18F]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 [18F]FDG-PET offers an important additional modality to explore brain networks. PMID:27349503

  6. Synthesis and evaluation of (S)-[(18)F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors.

    PubMed

    Pithia, Neema K; Liang, Christopher; Pan, Xiang-Zuo; Pan, Min-Liang; Mukherjee, Jogeshwar

    2016-04-15

    Serotonin 5-HT3 receptors are involved in various brain functions including as an emesis target during cancer chemotherapy. We report here the development of (S)-2,3-dimethoxy-5-(3'-[(18)F]fluoropropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide ([(18)F]fesetron) as a potential PET imaging agent for serotonin 5-HT3 receptors. By radiolabeling((S)-2,3-dimethoxy-5-(3'-tosyloxypropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide) with fluorine-18, (S)-[(18)F]fesetron was obtained in 5 to 10% decay-corrected yields and with specific activities >74GBq/μmol at the end of radiosynthesis. PET imaging in rats showed low uptake of [(18)F]fesetron in the brain with retention of binding in the striatal and cerebellar regions. Using colliculi as a reference region, ratios were 3.4 for striata and 2.5 for cerebellum. Ex vivo brain PET analysis displayed binding of [(18)F]fesetron in the hippocampus, striatum and cerebellar regions. Cerebellar regions corresponded to area postrema and nucleus tract solitaris known to contain 5-HT3 receptors. Dorsal hippocampus showed the highest uptake with ratio of >17 with respect to colliculi, while area postrema and striata had ratios of >10. Thus, [(18)F]fesetron exhibited a unique binding profile to rat brain regions known to contain significant amounts of serotonin 5-HT3 receptors. However, the very low brain uptake limits its usefulness as a PET radiotracer in this animal model. PMID:26979158

  7. Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood–Brain Barrier

    PubMed Central

    Bauer, M; Römermann, K; Karch, R; Wulkersdorfer, B; Stanek, J; Philippe, C; Maier‐Salamon, A; Haslacher, H; Jungbauer, C; Wadsak, W; Jäger, W; Löscher, W; Hacker, M; Zeitlinger, M

    2016-01-01

    ABCB1 and ABCG2 work together at the blood–brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([11C]elacridar and [11C]tariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single‐nucleotide polymorphism (SNP) c.421C>A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high‐dose tariquidar. In contrast to the ABCB1‐selective substrate (R)‐[11C]verapamil, [11C]elacridar and [11C]tariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in [11C]tariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function. PMID:26940368

  8. Pilot PET Study to Assess the Functional Interplay Between ABCB1 and ABCG2 at the Human Blood-Brain Barrier.

    PubMed

    Bauer, M; Römermann, K; Karch, R; Wulkersdorfer, B; Stanek, J; Philippe, C; Maier-Salamon, A; Haslacher, H; Jungbauer, C; Wadsak, W; Jäger, W; Löscher, W; Hacker, M; Zeitlinger, M; Langer, O

    2016-08-01

    ABCB1 and ABCG2 work together at the blood-brain barrier (BBB) to limit brain distribution of dual ABCB1/ABCG2 substrates. In this pilot study we used positron emission tomography (PET) to assess brain distribution of two model ABCB1/ABCG2 substrates ([(11) C]elacridar and [(11) C]tariquidar) in healthy subjects without (c.421CC) or with (c.421CA) the ABCG2 single-nucleotide polymorphism (SNP) c.421C>A. Subjects underwent PET scans under conditions when ABCB1 and ABCG2 were functional and during ABCB1 inhibition with high-dose tariquidar. In contrast to the ABCB1-selective substrate (R)-[(11) C]verapamil, [(11) C]elacridar and [(11) C]tariquidar showed only moderate increases in brain distribution during ABCB1 inhibition. This provides evidence for a functional interplay between ABCB1 and ABCG2 at the human BBB and suggests that both ABCB1 and ABCG2 need to be inhibited to achieve substantial increases in brain distribution of dual ABCB1/ABCG2 substrates. During ABCB1 inhibition c.421CA subjects had significantly higher increases in [(11) C]tariquidar brain distribution than c.421CC subjects, pointing to impaired cerebral ABCG2 function. PMID:26940368

  9. Functional brain mapping of the macaque related to spatial working memory as revealed by PET.

    PubMed

    Inoue, Masato; Mikami, Akichika; Ando, Ichiro; Tsukada, Hideo

    2004-01-01

    To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex. PMID:14654462

  10. F-18 Stilbenes As PET Imaging Agents For Detecting β-Amyloid Plaques In The Brain

    PubMed Central

    Zhang, Wei; Oya, Shunichi; Kung, Mei-Ping; Hou, Catherine; Maier, Donna L.; Kung, Hank F.

    2008-01-01

    Imaging agents targeting β,-amyloid (Aβ) may be useful for diagnosis and treatment of patients with Alzheimer’s disease (AD). Compounds 3e and 4e are fluorinated stilbene derivatives displaying high binding affinities for Aβ plaques in AD brain homogenates (Ki = 15 ± 6 and 5.0 ± 1.2 nM, respectively). In vivo biodistributions of [18F]3e and [18F]4e in normal mice exhibited excellent brain penetrations (5.55 and 9.75 % dose/g at 2 min) and rapid brain washouts were observed, especially for [18F]4e (0.72% dose/g at 60 min). They also showed in vivo plaque labeling in APP/PS1 or Tg2576 transgenic mice, animal models for AD. Autoradiography of postmortem AD brain sections and AD homogenate binding studies confirmed the selective and specific binding properties to Aβ plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [18F]3e and [18F]4e, are suitable candidates as Aβ plaque imaging agents for studying patients with AD. PMID:16162001

  11. Differentiation of extrastriatal dopamine D2 receptor density and affinity in the human brain using PET.

    PubMed

    Olsson, Hans; Halldin, Christer; Farde, Lars

    2004-06-01

    Dopaminergic neurotransmission in extrastriatal regions may play a crucial role in the pathophysiology and treatment of neuropsychiatric disorders. The high-affinity radioligands [(11)C]FLB 457, [(123)I]epidepride, and [(18)F]fallypride are now used in clinical studies to measure these low-density receptor populations in vivo. However, a single determination of the regional binding potential (BP) does not differentiate receptor density (B(max)) from the apparent affinity (K(D)). In this positron emission tomography (PET) study, we measured extrastriatal dopamine D2 receptor density (B(max)) and apparent affinity (K(D)) in 10 healthy subjects using an in vivo saturation approach. Each subject participated in two to three PET measurements with different specific radioactivity of [(11)C]FLB 457. The commonly used simplified reference tissue model (SRTM) was used in a comparison of BP values with the B(max) values obtained from the saturation analysis. The calculated regional receptor density values were of the same magnitude (0.33-1.68 nM) and showed the same rank order as reported from postmortem studies, that is, in descending order thalamus, lateral temporal cortex, anterior cinguli, and frontal cortex. The affinity ranged from 0.27 to 0.43 nM, that is, approximately 10-20 times the value found in vitro (20 pM). The area under the cerebellar time activity curve (TAC) was slightly lower (11 +/- 8%, mean +/- SD, P = 0.004, n = 10) after injection of low as compared with high specific radioactivity, indicating sensitivity to the minute density of dopamine D2 receptors in the this region. The results of the present study support that dopamine D2 receptor density and affinity can be differentiated in low-density regions using a saturation approach. There was a significant (P < 0.001) correlation between the binding potential calculated with SRTM and the receptor density (B(max)), which supports the use of BP in clinical studies where differentiation of B(max) and K

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

    SciTech Connect

    Biegon, A.; Biegon, A.; Kim, S.W.; Alexoff, D.; Millard, J.; Carter, P.; Hubbard, B.; King, P.; Logan, J.; Muench, L.; Pareto, D.; Schlyer, D.; Shea, C.; Telang, F.; Wang, G.-J.; Xu, Y.; Fowler, J.

    2010-10-01

    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-min 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.

  13. STRATEGIES FOR QUANTIFYING PET IMAGING DATA FROM TRACER STUDIES OF BRAIN RECEPTORS AND ENZYMES.

    SciTech Connect

    Logan, J.

    2001-04-02

    A description of some of the methods used in neuroreceptor imaging to distinguish changes in receptor availability has been presented in this chapter. It is necessary to look beyond regional uptake of the tracer since uptake generally is affected by factors other than the number of receptors for which the tracer has affinity. An exception is the infusion method producing an equilibrium state. The techniques vary in complexity some requiring arterial blood measurements of unmetabolized tracer and multiple time uptake data. Others require only a few plasma and uptake measurements and those based on a reference region require no plasma measurements. We have outlined some of the limitations of the different methods. Laruelle (1999) has pointed out that test/retest studies to which various methods can be applied are crucial in determining the optimal method for a particular study. The choice of method will also depend upon the application. In a clinical setting, methods not involving arterial blood sampling are generally preferred. In the future techniques for externally measuring arterial plasma radioactivity with only a few blood samples for metabolite correction will extend the modeling options of clinical PET. Also since parametric images can provide information beyond that of ROI analysis, improved techniques for generating such images will be important, particularly for ligands requiring more than a one-compartment model. Techniques such as the wavelet transform proposed by Turkheimer et al. (2000) may prove to be important in reducing noise and improving quantitation.

  14. Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

    PubMed

    Aupée, A M; Desgranges, B; Eustache, F; Lalevée, C; de la Sayette, V; Viader, F; Baron, J C

    2001-06-01

    In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology. PMID:11352622

  15. Development of a High Precision Axial 3-D PET for Brain Imaging

    NASA Astrophysics Data System (ADS)

    Bolle, E.; Braem, A.; Casella, C.; Chesi, E.; Clinthorne, N.; Cochran, E.; De Leo, R.; Dissertori, G.; Djambazov, L.; Honscheid, K.; Huh, S.; Johnson, I.; Joram, C.; Kagan, H.; Lacasta, C.; Lustermann, W.; Meddi, F.; Nappi, E.; Nessi-Tedaldi, F.; Oliver, J. F.; Pauss, F.; Rafecas, M.; Renker, D.; Rudge, A.; Schinzel, D.; Schneider, T.; Séguinot, J.; Smith, S.; Solevi, P.; Stapnes, S.; Vilardi, I.; Weilhammer, P.

    2009-12-01

    We describe a PET device based on a novel method to extract the coordinates of the interaction point of the 511keV γ rays from 100 mm long and thin LYSO (Lutetium Yttrium OxyorthoSilicate) scintillator bars, positioned axially in the tomograph. The coordinate along the hit crystal is measured by using a hodoscope of Wave Length Shifting (WLS) plastic strips mounted perpendicularly to each plane of scintillators. As photodetectors, new Geiger mode Avalanche PhotoDetectors (G-APDs) with integrated electronics are being used to detect both the hit crystal in a block (x and y coordinates) and the interaction point in the crystal (z coordinate) through the light escaping from the crystal and transmitted to the WLS strips. In this way, the γ interaction point can be determined with a spatial resolution of few cubic millimeters down to a minimum deposited energy of about 50 keV, resulting in a volumetric precision very close to the limits imposed by the physics of the positron annihilation. The method allows to increase the detection efficiency without affecting the spatial resolution by adding scintillator planes in the radial direction. A demonstrator scanner, based on two matrices of 8 × 6 LYS crystals and 312 WLS strips, slotted in between the crystals, is under construction. Preliminary results from the feasibility studies of the various components will be presented.

  16. Brain and Whole-Body Imaging in Rhesus Monkeys of 11C-NOP-1A, a Promising PET Radioligand for Nociceptin/Orphanin FQ Peptide Receptors

    PubMed Central

    Kimura, Yasuyuki; Fujita, Masahiro; Hong, Jinsoo; Lohith, Talakad G.; Gladding, Robert L.; Zoghbi, Sami S.; Tauscher, Johannes A.; Goebl, Nancy; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepcion; Barth, Vanessa N.; Pike, Victor W.; Innis, Robert B.

    2011-01-01

    Our laboratory developed (S)-3-(2′-fluoro-6′,7′-dihydrospiro [piperidine-4,4′-thieno[3,2-c]pyran]-1-yl)-2-(2-fluorobenzyl)-N-methylpropanamide (11C-NOP-1A), a new radioligand for the nociceptin/orphanin FQ peptide (NOP) receptor, with high affinity (Ki, 0.15 nM) and appropriate lipophilicity (measured logD, 3.4) for PET brain imaging. Here, we assessed the utility of 11C-NOP-1A for quantifying NOP receptors in the monkey brain and estimated the radiation safety profile of this radioligand based on its biodistribution in monkeys. Methods Baseline and blocking PET scans were acquired from head to thigh for 3 rhesus monkeys for approximately 120 min after 11C-NOP-1A injection. These 6 PET scans were used to quantify NOP receptors in the brain and to estimate radiation exposure to organs of the body. In the blocked scans, a selective nonradioactive NOP receptor antagonist (SB-612111; 1 mg/kg intravenously) was administered before 11C-NOP-1A. In all scans, arterial blood was sampled to measure the parent radioligand 11C-NOP-1A. Distribution volume (VT; a measure of receptor density) was calculated with a compartment model using brain and arterial plasma data. Radiation-absorbed doses were calculated using the MIRD Committee scheme. Results After 11C-NOP-1A injection, peak uptake of radioactivity in the brain had a high concentration (~5 standardized uptake value), occurred early (~12 min), and thereafter washed out quickly. VT (mL cm−3) was highest in the neocortex (~20) and lowest in hypothalamus and cerebellum (~13). SB-612111 blocked approximately 50%–70% of uptake and reduced VT in all brain regions to approximately 7 mL cm−3. Distribution was well identified within 60 min of injection and stable for the remaining 60 min, consistent with only parent radioligand and not radiometabolites entering the brain. Whole-body scans confirmed that the brain had specific (i.e., displaceable) binding but could not detect specific binding in peripheral organs. The

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

    PubMed Central

    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 [18F]-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 (Rmean = 0.75) was slightly superior to the brainstem (Rmean = 0.74) and the cerebellum (Rmean = 0.73). Automated brain

  18. Single-subject statistical mapping of acute brain hypoxia in the rat following middle cerebral artery occlusion: a microPET study.

    PubMed

    Takasawa, Masashi; Beech, John S; Fryer, Tim D; Jones, P Simon; Ahmed, Tahir; Smith, Rob; Aigbirhio, Franklin I; Baron, Jean-Claude

    2011-06-01

    No study so far has attempted to map the 3D topography of brain hypoxia in the individual rat in vivo following middle cerebral artery occlusion (MCAo). In a previous microPET study, we reported that (18)F-fluoromisonidazole ((18)F-MISO) trapping in the brain after MCAo was specific for the hypoxic viable tissue. Here, we used (18)F-MISO microPET to map the 3D topography of brain hypoxia in the acute stage of permanent distal MCAo in individual spontaneously hypertensive rats. Normal rats were also studied. (18)F-MISO was intravenously injected approximately 1 h after clip placement and PET data were acquired for 2 hours. Animals were sacrificed and the brains harvested 48 h later for infarct mapping using standard histopathology. As expected, continuous (18)F-MISO trapping was found over the affected relative to unaffected and control MCA cortex. Using single-subject voxel-based statistical mapping, tracer accumulation 90-120 min after injection was consistently significantly higher in the anterior MCA cortex (proximal relative to clip site) and gradually decreased towards posterior areas, a pattern consistent with the classic penumbra concept. The data also suggested that (i) a portion of the significant (18)F-MISO trapping area may sit outside the contours of the final infarct despite the permanent MCAo, suggesting that (18)F-MISO may be a marker not only of severe (penumbral) but also of milder (oligemic) hypoxia, and (ii) small portions of the final infarct may not exhibit early tracer trapping, suggesting that by the time the tracer was administered this tissue had already progressed to irreversible damage. This study shows the feasibility of single-subject mapping of brain hypoxia following MCAo in the rat, which has potential applications in pathophysiological investigations. PMID:21335004

  19. Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study

    PubMed Central

    Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

    2016-01-01

    Objective 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. Methods 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. Results 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. Conclusions 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. PMID:27529342

  20. An Interindividual Comparison of O-(2- [{sup 18}F]Fluoroethyl)-L-Tyrosine (FET)- and L-[Methyl-{sup 11}C]Methionine (MET)-PET in Patients With Brain Gliomas and Metastases

    SciTech Connect

    Grosu, Anca-Ligia; Astner, Sabrina T.; Riedel, Eva; Nieder, Carsten; Wiedenmann, Nicole; Heinemann, Felix; Schwaiger, Markus; and others

    2011-11-15

    Purpose: L-[methyl-{sup 11}C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of {sup 11}C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2- [{sup 18}F]fluoroethyl)-L-tyrosine (FET) is labeled with {sup 18}F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI). Methods and Materials: We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up. Results: There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 {+-} 1.01 and 2.33 {+-} 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%. Conclusions: O-(2- [{sup 18}F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic

  1. 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. PMID:22948355

  2. Synthesis of (R)- and (S)-[C-11]L-365,260 for PET studies of brain cholecystokinin (CCK) receptors

    SciTech Connect

    Haradahira, T.; Suzuki, K.; Inoue, O.

    1994-05-01

    Cholecystokinin (CCK) is a recognized peptide hormone in the gut and proposed as a neurotransmitter or neuromodulator in the central nervous system. Two distinct CCK receptors termed CCK-A and CCK-B have been characterized. CCK-A receptor is primarily distributed in the peripheral tissues including pancreas and gallbladder and also known to be distributed in a few brain regions. CCK-B receptor is widely distributed in the brain and has been proposed to be involved in anxiety, satiety and nociception. To investigate the functional roles of the CCK receptors in the brain by positron emission tomography, we have synthesized an enantiomeric pair of C-11 labeled non-peptide antagonists against the CCK receptors. L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl)-N`-(3-methylpheny lurea)] is a potent CCK-B selective non-peptide antagonist (CCK-A/CCK-B ratio of IC50, 140), whereas its (S)-enantiomer is selective toward CCK-A receptor (CCK-A/CCK-B ratio of IC50, 0.02). We have synthesized the (R)- and (S)-enantiomers of [C-11]-365,260 by N-methylation (50{degrees}C for 5 min) of the racemic desmethyl precursor with [C-11]iodomethane using sodium hydride as a base and subsequent optical resolution with HPLC (column: ChiraSpher, 250 x 10 mm, Merck; eluent: n-hexane / 1,4-dioxane / 2-propanol / triethylamine = 70 / 25 / 5 / 0.1). Radiochemical yields (decay corrected) and optical purities were 34%, 99% for R-enantiomer and 36%, 99% for S-enantiomer, respectively. The total synthesis time was 40 min and specific activity was about 37 GBq/{mu}mol. In PET studies on rhesus monkey (R)-enantiomer showed a high uptake of radioactivity in the cerebral cortex, region known to have a high concentration of CCK-B receptor.

  3. The countrate performance of the volume imaging PENN-PET scanner

    SciTech Connect

    Smith, R.J.; Karp, J.S. . Dept. of Radiology); Muehllehner, G. )

    1994-12-01

    The UGM PENN-PET Camera uses large position sensitive detectors and operates without septa. This design results in high sensitivity and 3-D imaging capability, but poses problems in high countrate situations. The maximum true countrates and random countrates have been measured, as a function of object size in the field-of-view. The countrate performance is understood in terms of the limiting process rates and event rejection in the camera. In addition, the camera is calibrated to generate absolute activity concentrations to within 5% by correcting for system deadtime with up to 3 mCi in the field of view in brain studies. This allows the performance of a variety of brain and body studies, and accurate quantitation of the data over a wide-range of imaging countrates, from [sup 18]F-FDG brain studies to [sup 15]O-water dynamic brain studies.

  4. Increase of 20-HETE synthase after brain ischemia in rats revealed by PET study with 11C-labeled 20-HETE synthase-specific inhibitor

    PubMed Central

    Kawasaki, Toshiyuki; Marumo, Toshiyuki; Shirakami, Keiko; Mori, Tomoko; Doi, Hisashi; Suzuki, Masaaki; Watanabe, Yasuyoshi; Chaki, Shigeyuki; Nakazato, Atsuro; Ago, Yukio; Hashimoto, Hitoshi; Matsuda, Toshio; Baba, Akemichi; Onoe, Hirotaka

    2012-01-01

    20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite known to be produced after cerebral ischemia, has been implicated in ischemic and reperfusion injury by mediating vasoconstriction. To develop a positron emission tomography (PET) probe for 20-HETE synthase imaging, which might be useful for monitoring vasoconstrictive processes in patients with brain ischemia, we synthesized a 11C-labeled specific 20-HETE synthase inhibitor, N′(4-dimethylaminohexyloxy)phenyl imidazole ([11C]TROA). Autoradiographic study showed that [11C]TROA has high-specific binding in the kidney and liver consistent with the previously reported distribution of 20-HETE synthase. Using transient middle cerebral artery occlusion in rats, PET study showed significant increases in the binding of [11C]TROA in the ipsilateral hemisphere of rat brains after 7 and 10 days, which was blocked by co-injection of excess amounts of TROA (10 mg/kg). The increased [11C]TROA binding on the ipsilateral side returned to basal levels within 14 days. In addition, quantitative real-time PCR revealed that increased expression of 20-HETE synthase was only shown on the ipsilateral side on day 7. These results indicate that [11C]TROA might be a useful PET probe for imaging of 20-HETE synthase in patients with cerebral ischemia. PMID:22669478

  5. Assessment of accuracy of PET utilizing a 3-D phantom to simulate the activity distribution of ( sup 18 F)fluorodeoxyglucose uptake in the human brain

    SciTech Connect

    Hoffman, E.J.; Cutler, P.D.; Guerrero, T.M.; Digby, W.M.; Mazziotta, J.C. )

    1991-03-01

    A three-dimensional brain phantom has been developed to simulate the activity distributions found in human brain studies currently employed in positron emission tomography (PET). The phantom has a single contiguous chamber and utilizes thin layers of lucite to provide apparent relative concentrations of 5, 1, and 0 for gray matter, white matter, and CSF structures, respectively. The phantom and an ideal image set were created from the same set of data. Thus, the user has a basis for comparing measured images with an ideal set that allows a quantitative evaluation of errors in PET studies with an activity distribution similar to that found in patients. The phantom was employed in a study of the effect of deadtime and scatter on accuracy in quantitation on a current PET system. Deadtime correction factors were found to be significant (1.1-2.5) at count rates found in clinical studies. Deadtime correction techniques were found to be accurate to within 5%. Scatter in emission and attenuation correction data consistently caused 5-15% errors in quantitation, whereas correction for scatter in both types of data reduced errors in accuracy to less than 5%.

  6. Differentiation of Brain Tumor Recurrence from Post-Radiotherapy Necrosis with 11C-Methionine PET: Visual Assessment versus Quantitative Assessment

    PubMed Central

    Minamimoto, Ryogo; Saginoya, Toshiyuki; Kondo, Chisato; Tomura, Noriaki; Ito, Kimiteru; Matsuo, Yuka; Matsunaga, Shigeo; Shuto, Takashi; Akabane, Atsuya; Miyata, Yoko; Sakai, Shuji; Kubota, Kazuo

    2015-01-01

    Purpose The aim of this multi-center study was to assess the diagnostic capability of visual assessment in L-methyl-11C-methionine positron emission tomography (MET-PET) for differentiating a recurrent brain tumor from radiation-induced necrosis after radiotherapy, and to compare it to the accuracy of quantitative analysis. Methods A total of 73 brain lesions (glioma: 31, brain metastasis: 42) in 70 patients who underwent MET-PET were included in this study. Visual analysis was performed by comparison of MET uptake in the brain lesion with MET uptake in one of four regions (around the lesion, contralateral frontal lobe, contralateral area, and contralateral cerebellar cortex). The concordance rate and logistic regression analysis were used to evaluate the diagnostic ability of visual assessment. Receiver-operating characteristic curve analysis was used to compare visual assessment with quantitative assessment based on the lesion-to-normal (L/N) ratio of MET uptake. Results Interobserver and intraobserver κ-values were highest at 0.657 and 0.714, respectively, when assessing MET uptake in the lesion compared to that in the contralateral cerebellar cortex. Logistic regression analysis showed that assessing MET uptake in the contralateral cerebellar cortex with brain metastasis was significantly related to the final result. The highest area under the receiver-operating characteristic curve (AUC) with visual assessment for brain metastasis was 0.85, showing no statistically significant difference with L/Nmax of the contralateral brain (AUC = 0.89) or with L/Nmean of the contralateral cerebellar cortex (AUC = 0.89), which were the areas that were the highest in the quantitative assessment. For evaluation of gliomas, no specific candidate was confirmed among the four areas used in visual assessment, and no significant difference was seen between visual assessment and quantitative assessment. Conclusion The visual assessment showed no significant difference from

  7. Bias in iterative reconstruction of low-statistics PET data: benefits of a resolution model

    NASA Astrophysics Data System (ADS)

    Walker, M. D.; Asselin, M.-C.; Julyan, P. J.; Feldmann, M.; Talbot, P. S.; Jones, T.; Matthews, J. C.

    2011-02-01

    Iterative image reconstruction methods such as ordered-subset expectation maximization (OSEM) are widely used in PET. Reconstructions via OSEM are however reported to be biased for low-count data. We investigated this and considered the impact for dynamic PET. Patient listmode data were acquired in [11C]DASB and [15O]H2O scans on the HRRT brain PET scanner. These data were subsampled to create many independent, low-count replicates. The data were reconstructed and the images from low-count data were compared to the high-count originals (from the same reconstruction method). This comparison enabled low-statistics bias to be calculated for the given reconstruction, as a function of the noise-equivalent counts (NEC). Two iterative reconstruction methods were tested, one with and one without an image-based resolution model (RM). Significant bias was observed when reconstructing data of low statistical quality, for both subsampled human and simulated data. For human data, this bias was substantially reduced by including a RM. For [11C]DASB the low-statistics bias in the caudate head at 1.7 M NEC (approx. 30 s) was -5.5% and -13% with and without RM, respectively. We predicted biases in the binding potential of -4% and -10%. For quantification of cerebral blood flow for the whole-brain grey- or white-matter, using [15O]H2O and the PET autoradiographic method, a low-statistics bias of <2.5% and <4% was predicted for reconstruction with and without the RM. The use of a resolution model reduces low-statistics bias and can hence be beneficial for quantitative dynamic PET.

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

    PubMed Central

    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

    2015-01-01

    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)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[11C]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. PMID:25669913

  9. 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. PMID:25669913

  10. Comparison of visual and ROI-based brain tumour grading using 18F-FDG PET: ROC analyses.

    PubMed

    Meyer, P T; Schreckenberger, M; Spetzger, U; Meyer, G F; Sabri, O; Setani, K S; Zeggel, T; Buell, U

    2001-02-01

    Several studies have suggested that the use of simple visual interpretation criteria for the investigation of brain tumours by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) might be similarly or even more accurate than quantitative or semi-quantitative approaches. We investigated this hypothesis by comparing the accuracy of FDG-PET brain tumour grading using a proposed six-step visual grading scale (VGS; applied by three independent observers unaware of the clinical history and the results of histopathology) and three different region of interest (ROI) ratios (maximal tumour uptake compared with contralateral tissue [Tu/Tis], grey matter [Tu/GM] and white matter [Tu/WM]). The patient population comprised 47 patients suffering from 17 benign (7 gliomas of grade II, 10 non-gliomatous tumours) and 30 malignant (23 gliomas of grade III-IV, 7 non-gliomatous tumours) tumours. The VGS results were highly correlated with the different ROI ratios (R=0.91 for Tu/GM, R=0.82 for Tu/WM, and R=0.79 for Tu/Tis), and high inter-observer agreement was achieved (kappa=0.63, 0.76 and 0.81 for the three observers). The mean ROI ratios and VGS readings of gliomatous and non-gliomatous lesions were not significantly different. For all measures, high-grade lesions showed significantly higher FDG uptake than low-grade lesions (P<0.005 to P<0.0001, depending on the measure used). Nominal logistic regressions and receiver operating characteristic (ROC) analyses were used to calculate cut-off values to differentiate low- from high-grade lesions. The predicted (by ROC) diagnostic sensitivity/specificity of the different tests (cut-off ratios shown in parentheses) were: Tu/GM: 0.87/0.85 (0.7), Tu/WM: 0.93/0.80 (1.3). Tu/Tis: 0.80/0.80 (0.8) and VGS: 0.84/0.95 (uptake < GM, but > WM). The VGS yielded the highest Az (+/-SE) value (i.e. area under the ROC curve as a measure of predicted accuracy), 0.97+/-0.03, which showed a strong tendency towards being significantly

  11. Preclinical evaluation of a promising C-11 labeled PET tracer for imaging phosphodiesterase 10A in the brain of living subject.

    PubMed

    Liu, Hui; Jin, Hongjun; Yue, Xuyi; Zhang, Xiang; Yang, Hao; Li, Junfeng; Flores, Hubert; Su, Yi; Perlmutter, Joel S; Tu, Zhude

    2015-11-01

    Phosphodiesterase 10A (PDE10A) plays a key role in the regulation of brain striatal signaling. A PET tracer for PDE10A may serve as a tool to evaluate PDE10A expression in vivo in central nervous system disorders with striatal pathology. Here, we further characterized the binding properties of a previously reported radioligand we developed for PDE10A, [(11)C]TZ1964B, in rodents and nonhuman primates (NHPs). The tritiated counterpart [(3)H]TZ1964B was used for in vitro binding characterizations in rat striatum homogenates and in vitro autoradiographic studies in rat brain slices. The carbon-11 labeled [(11)C]TZ1964B was utilized in the ex vivo autoradiography studies for the brain of rats and microPET imaging studies for the brain of NHPs. MicroPET scans of [(11)C]TZ1964B in NHPs were conducted at baseline, as well as with using a selective PDE10A inhibitor MP-10 for either pretreatment or displacement. The in vivo regional target occupancy (Occ) was obtained by pretreating with different doses of MP-10 (0.05-2.00 mg/kg). Both in vitro binding assays and in vitro autoradiographic studies revealed a nanomolar binding affinity of [(3)H]TZ1964B to the rat striatum. The striatal binding of [(3)H]TZ1964B and [(11)C]TZ1964B was either displaced or blocked by MP-10 in rats and NHPs. Autoradiography and microPET imaging confirmed that the specific binding of the radioligand was found in the striatum but not in the cerebellum. Blocking studies also confirmed the suitability of the cerebellum as an appropriate reference region. The binding potentials (BPND) of [(11)C]TZ1964B in the NHP striatum that were calculated using either the Logan reference model (LoganREF, 3.96 ± 0.17) or the simplified reference tissue model (SRTM, 4.64 ± 0.47), with the cerebellum as the reference region, was high and had good reproducibility. The occupancy studies indicated a MP-10 dose of 0.31 ± 0.09 mg/kg (LoganREF)/0.45 ± 0.17mg/kg (SRTM) occupies 50% striatal PDE10A binding sites. Studies

  12. Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand 11C-NOP-1A

    PubMed Central

    Lohith, Talakad G.; Zoghbi, Sami S.; Morse, Cheryl L.; Araneta, Maria F.; Barth, Vanessa N.; Goebl, Nancy A.; Tauscher, Johannes T.; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro

    2013-01-01

    Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high-affinity PET ligand, 11C-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of 11C-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile. Methods After intravenous injection of 11C-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (VT; a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise’s bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose). Results After 11C-NOP-1A injection, the peak concentration of radioactivity in brain was high (~5–7 standardized uptake values), occurred early (~10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent VT identifiability (~1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional VT values (mL·cm−3) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. VT was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of 11C-NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 VT values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. 11C-NOP-1A was significantly

  13. Clinical Value of [{sup 11}C]Methionine PET for Stereotactic Radiation Therapy With Intensity Modulated Radiation Therapy to Metastatic Brain Tumors

    SciTech Connect

    Miwa, Kazuhiro; Matsuo, Masayuki; Shinoda, Jun; Aki, Tatsuki; Yonezawa, Shingo; Ito, Takeshi; Asano, Yoshitaka; Yamada, Mikito; Yokoyama, Kazutoshi; Yamada, Jitsuhiro; Yano, Hirohito; Iwama, Toru

    2012-12-01

    Purpose: This study investigated the clinical impact of {sup 11}C-labeled methionine-positron emission tomography (MET-PET) for stereotactic radiation therapy with intensity modulated radiation therapy (SRT-IMRT) in metastatic brain tumors. Methods and Materials: Forty-two metastatic brain tumors were examined. All tumors were treated with SRT-IMRT using a helical tomotherapy system. Gross tumor volume (GTV) was defined and drawn on the stereotactic magnetic resonance (MR) image, taking into account the respective contributions of MR imaging and MET-PET. Planning target volume (PTV) encompassed the GTV-PET plus a 2-mm margin. SRT-IMRT was performed, keeping the dose for PTV at 25-35 Gy in 5 fractions. The ratio of the mean value of MET uptake to the contralateral normal brain (L/N ratio) was plotted for the PTV prior to SRT-IMRT, at 3 months following SRT-IMRT, and at 6 months following SRT-IMRT. Tumor characteristic changes of MET uptake before and after SRT-IMRT were evaluated quantitatively, comparing them with MRI examination. Results: Mean {+-} SD L/N ratios were 1.95 {+-} 0.83, 1.18 {+-} 0.21, and 1.12 {+-} 0.25 in the pre-SRT-IMRT group, in the 3 months post-SRT-IMRT group, and in the 6 months post-SRT-IMRT group, respectively. Differences in the mean L/N ratio between the pre-SRT-IMRT group and the 3-month post-SRT-IMRT group and between the pre-SRT-IMRT group and the 6 month post-SRT-IMRT group were statistically significant, irrespective of MRI examination. Conclusions: We showed examples of metastatic lesions demonstrating significant decreases in MET uptake following SRT-IMRT. MET-PET seems to have a potential role in providing additional information, although MRI remains the gold standard for diagnosis and follow-up after SRT-IMRT. The present study is a preliminary approach, but to more clearly define the impact of PET-based radiosurgical assessment, further experimental and clinical analyses are required.

  14. SPECT studies of brain tumors with L-3-( sup 123 I) iodo-alpha-methyl tyrosine: Comparison with PET, 124IMT and first clinical results

    SciTech Connect

    Langen, K.J.; Coenen, H.H.; Roosen, N.; Kling, P.; Muzik, O.; Herzog, H.; Kuwert, T.; Stoecklin, G.F.; Feinendegen, L.E. )

    1990-03-01

    L-3-({sup 123}I)iodo-alpha-methyltyrosine ({sup 123}IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of {sup 124}IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). {sup 124}IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with {sup 123}IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, {sup 123}IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.

  15. Correlation of amyloid PET ligand florbetapir F 18 (18F-AV-45) binding with β-amyloid aggregation and neuritic plaque deposition in postmortem brain tissue

    PubMed Central

    Choi, Seok Rye; Schneider, Julie A.; Bennett, David A.; Beach, Thomas G.; Bedell, Barry J.; Zehntner, Simone P.; Krautkramer, Michael; Kung, Hank F.; Skovronsky, Daniel M.; Hefti, Franz; Clark, Christopher M.

    2011-01-01

    Background Florbetapir F 18 (18F-AV-45) is a positron emission tomography (PET) imaging ligand for the detection of amyloid aggregation associated with Alzheimer’s disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid plaques in human brain homogenates (Kd = 3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. The present study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and β-amyloid density measured by established neuropathological methods. Methods The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 subjects with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of β-amyloid identified by silver staining, thioflavin S staining, and immunohistochemistry. Results There were strong quantitative correlations between florbetapir F 18 tissue binding and both β-amyloid plaques identified by light microscopy (sliver staining and thioflavin S fluorescence) and by immunohistochemical measurements of β-amyloid using three antibodies recognizing different epitopes of the β-amyloid peptide (Aβ). Florbetapir F 18 did not bind to neurofibrillary tangles. Conclusion Florbetapir F 18 selectively binds β-amyloid in human brain tissue. The binding intensity was quantitatively correlated with the density of β-amyloid plaques identified by standard neuropathological techniques and correlated with the density of Aβ measured by immunohistochemistry. Since β-amyloid plaques are a defining neuropathological feature for Alzheimer’s disease, these results support the use of florbetapir F 18 as an amyloid PET ligand to identify the presence of AD pathology in patients with signs and symptoms of progressive late-life cognitive

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

    SciTech Connect

    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 pure {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.

  17. Quantification of [(11)C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography.

    PubMed

    Veronese, Mattia; Bodini, Benedetta; García-Lorenzo, Daniel; Battaglini, Marco; Bongarzone, Salvatore; Comtat, Claude; Bottlaender, Michel; Stankoff, Bruno; Turkheimer, Federico E

    2015-11-01

    An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers <1%) and reproducibility (intraclass correlation coefficient (ICC) >0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins. PMID:26058700

  18. Assessment of Brain Damage and Plasticity in the Visual System Due to Early Occipital Lesion: Comparison of FDG-PET with Diffusion MRI Tractography

    PubMed Central

    Jeong, Jeong-won; Tiwari, Vijay N.; Shin, Joseph; Chugani, Harry T.; Juhász, Csaba

    2015-01-01

    Purpose To determine the relation between glucose metabolic changes of the primary visual cortex, structural abnormalities of the corresponding visual tracts, and visual symptoms in children with Sturge-Weber syndrome (SWS). Materials and Methods In 10 children with unilateral SWS (ages 1.5–5.5 years), a region-of-interest analysis was applied in the bilateral medial occipital cortex on positron emission tomography (PET) and used to track diffusion-weighted imaging (DWI) streamlines corresponding to the central visual pathway. Normalized streamline volumes of individual SWS patients were compared with values from age-matched control groups as well as correlated with normalized glucose uptakes and visual field deficit. Results Lower glucose uptake and lower corresponding streamline volumes were detected in the affected occipital lobe in 9/10 patients, as compared to the contralateral side. Seven of these 9 patients had visual field deficit and normal or decreased streamline volumes on the unaffected side. The two other children had no visual symptoms and showed high contralateral visual streamline volumes. There was a positive correlation between the normalized ratios on DWI and PET, indicating that lower glucose metabolism was associated with lower streamline volume in the affected hemisphere (R = 0.70, P = 0.024). Conclusion We demonstrated that 18F-flurodeoxyglucose (FDG)-PET combined with DWI tractography can detect both brain damage on the side of the lesion and contralateral plasticity in children with early occipital lesions. PMID:24391057

  19. Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging.

    PubMed

    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 J; Patnaik, Debasis; Wagner, Florence F; Perlis, Roy; Holson, Edward B; Haggarty, Stephen J; El Fakhri, Georges; Kurumbail, Ravi G; Vasdev, Neil

    2016-08-01

    Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated 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 (11) C-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

  20. Comparison of [11C]cocaine binding at tracer and pharmacological doses of baboon brain: A PET study

    SciTech Connect

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

    1994-05-01

    In vitro studies have shown that cocaine (C) binds to both high and low affinity sites on the dopamine transporter (DAT). We have previously characterized the binding of tracer doses of [{sup 11}C]cocaine (C*)to a high affinity site on the DAT. To assess if in vivo C also binds to low affinity sites we used PET to compare binding of tracer doses (17.8{plus_minus}12.2 {mu}g C) of C* to pharmacological doses (8 mg of C coadministered with C*). Sixteen paired studies were done to assess test/retest variability, specific versus non specific binding and to characterize binding profile. Dynamic scans were started immediately after injection of C* (5-8 mCi) for 50 min on the CTI-931 (6 x 6 x 6.5 mm FWHM). Time activity curves for tissue concentration and for unchanged tracer in plasma were used to calculate the transport constant between plasma and tissue (K1) and to obtain the distribution volume (DV). The ratio of the DV in striatum (ST) to that in cerebellum (CB) (which corresponds to Bmax/Kd-1) was used as model parameter. Peak brain uptake of C* was significantly higher for tracer than for pharmacological doses (0.041 versus 0.033 % dose/cc), as were the values for K1 (1.07{plus_minus}0.21 versus 0.68{plus_minus}0.26 (t=3.0 p<0.01)). Repeated measures were reproducible for tracer ({plus_minus}2%) and pharmacological doses of C* ({plus_minus}4%). Tracer dose C* showed highest binding and slowest clearance in ST which was reduced by C (0.5-2.0 mg/kg iv, -25 to -30%) and by drugs that inhibit DAT (2mg/kg nomifensine - 21%, 0.5 mg/kg methylphenidate -12%) and was increased by serotonin transporter inhibitors (5HT-Ti) (2 mg/kg citalopram +11%, 0.5 mg/kg fluoxetine +6%) and not changed by NE transporter inhibitors (0.5 mg/kg desipramine or 2 mg/kg tomoxetine). The increase with (5HT-Ti) may reflect neurotransmitter interactions or changes in bioavailability. At pharmacological doses C* showed homogeneous distribution and was not changed by C nor by any of the above drugs.

  1. A standardized method for the construction of tracer specific PET and SPECT rat brain templates: validation and implementation of a toolbox.

    PubMed

    Vállez Garcia, David; Casteels, Cindy; Schwarz, Adam J; Dierckx, Rudi A J O; Koole, Michel; Doorduin, Janine

    2015-01-01

    High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70 ± 0.32 mm for [18F]FDG (n = 25), 0.23 ± 0.10mm for [11C]flumazenil (n = 13), 0.88 ± 0.20 mm for [11C]MeDAS (n = 15), 0.64 ± 0.28 mm for [11C]PK11195 (n = 19), 0.34 ± 0.15 mm for [11C]raclopride (n = 6), and 0.40 ± 0.13 mm for [99mTc]HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p<0.001). Additionally, registration errors were smallest with strain-specific templates (p<0.05), and when images and templates had the same size (p ≤ 0.001). Moreover, highest registration errors were found for the focal lesion group (p<0.005) and the diffuse lesion group (p = n.s.). In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer

  2. A Standardized Method for the Construction of Tracer Specific PET and SPECT Rat Brain Templates: Validation and Implementation of a Toolbox

    PubMed Central

    Vállez Garcia, David; Casteels, Cindy; Schwarz, Adam J.; Dierckx, Rudi A. J. O.; Koole, Michel; Doorduin, Janine

    2015-01-01

    High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70±0.32mm for [18F]FDG (n = 25), 0.23±0.10mm for [11C]flumazenil (n = 13), 0.88±0.20 mm for [11C]MeDAS (n = 15), 0.64±0.28mm for [11C]PK11195 (n = 19), 0.34±0.15mm for [11C]raclopride (n = 6), and 0.40±0.13mm for [99mTc]HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p&0.001). Additionally, registration errors were smallest with strain-specific templates (p&0.05), and when images and templates had the same size (p≤0.001). Moreover, highest registration errors were found for the focal lesion group (p&0.005) and the diffuse lesion group (p = n.s.). In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer-specific templates allows

  3. In vivo PET imaging of the α4β2 nicotinic acetylcholine receptor as a marker for brain inflammation after cerebral ischemia.

    PubMed

    Martín, Abraham; Szczupak, Boguslaw; Gómez-Vallejo, Vanessa; Domercq, Maria; Cano, Ainhoa; Padro, Daniel; Muñoz, Clara; Higuchi, Makoto; Matute, Carlos; Llop, Jordi

    2015-04-15

    PET imaging of nicotinic acetylcholine receptors (nAChRs) could become an effective tool for the diagnosis and therapy evaluation of neurologic diseases. Despite this, the role of nAChRs α4β2 receptors after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. To investigate this, we performed in parallel in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 at 1, 3, 7, 14, 21, and 28 d after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 showed a progressive binding increase from days 3-7, followed by a progressive decrease from days 14-28 after cerebral ischemia onset. Ex vivo immunohistochemistry for the nicotinic α4β2 receptor and the mitochondrial translocator protein (18 kDa) (TSPO) confirmed the PET findings and demonstrated the overexpression of α4β2 receptors in both microglia/macrophages and astrocytes from days 7-28 after experimental ischemic stroke. Likewise, the role played by α4β2 receptors on neuroinflammation was supported by the increase of [(11)C]PK11195 binding in ischemic rats treated with the α4β2 antagonist dihydro-β-erythroidine hydrobromide (DHBE) at day 7 after MCAO. Finally, both functional and behavioral testing showed major impaired outcome at day 1 after ischemia onset, followed by a recovery of the sensorimotor function and dexterity from days 21-28 after experimental stroke. Together, these results suggest that the nicotinic α4β2 receptor could have a key role in the inflammatory reaction underlying cerebral ischemia in rats. PMID:25878273

  4. Washout rate in rat brain irradiated by a 11C beam after acetazolamide loading using a small single-ring OpenPET prototype

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Takuwa, Hiroyuki; Yoshida, Eiji; Nishikido, Fumihiko; Nakajima, Yasunori; Wakizaka, Hidekatsu; Yamaya, Taiga

    2016-03-01

    In dose verification techniques of particle therapies based on in-beam positron emission tomography (PET), the causes of washout of positron emitters by physiological effects should be clarified to correct washout for accurate verification. As well, the quantitative washout rate has a potential usefulness as a diagnostic index which should be explored. Therefore, we measured washout rates of rat brain after vasodilator acetazolamide loading to investigate the possible effects of blood flow on washout. Six rat brains were irradiated by a radioisotope 11C beam and time activity curves on the whole brains were obtained with a small single-ring OpenPET prototype. Then, washout rates were calculated with the Mizuno model, where two washout rates (k 2m and k 2s ) were assumed, and a two-compartment model including efflux from tissue to blood (k 2) and influx (k 3) and efflux (k 4) between the two tissue compartments. Before the irradiations, we used laser-Doppler flowmetry to confirm that acetazolamide increased cerebral blood flow (CBF) of a rat. We compared means of k 2m , k 2s and k 2, k 3 and k 4 without acetazolamide loading (Rest) and with acetazolamide loading (ACZ). For all k values, ACZ values were lower than Rest values. In other words, though CBF increased, washout rates were decreased. This may be attributed to the implanted 11C reacting to form 11CO2. Because acetazolamide increased the concentration of CO2 in brain, suppressed diffusion of 11CO2 and decomposition of 11CO2 into ions were prevented.

  5. Evaluation in Monkey of Two Candidate PET Radioligands, [11C]RX-1 and [18F]RX-2, for Imaging Brain 5-HT4 Receptors

    PubMed Central

    LOHITH, TALAKAD G.; XU, RONG; TSUJIKAWA, TETSUYA; MORSE, CHERYL L.; ANDERSON, KACEY B.; GLADDING, ROBERT L.; ZOGHBI, SAMI S.; FUJITA, MASAHIRO; INNIS, ROBERT B.; PIKE, VICTOR W.

    2014-01-01

    The serotonin subtype-4 (5-HT4) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer’s disease, anxiety and other neuropsychiatric disorders – has few radioligands readily available for imaging in vivo. We have previously reported two novel 5-HT4 receptor radioligands, namely [methoxy-11C](1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]RX-1) and the [18F]3-fluoromethoxy analog ([18F]RX-2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5-HT4 receptor antagonist, on the same day for [11C]RX-1 and on different days for [18F]RX-2. Specific-to-nondisplaceable ratio (BPND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (VT) was also measured in some monkeys by radiometabolite-corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BPND values were in the rank order of known 5-HT4 receptor distribution with a trend for higher BPND values from [18F]RX-2. One-tissue compartmental model provided good fits with well identified VT values for both radioligands. In the highest 5-HT4 receptor density region, striatum, 50–60% of total binding was specific. The VT in receptor-poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [11C]RX-1 and [18F]RX-2 showed positive attributes for PET imaging of brain 5-HT4 receptors, validating the radioligand design strategy. PMID:25088028

  6. Acute increases in synaptic GABA detectable in the living human brain: a [¹¹C]Ro15-4513 PET study.

    PubMed

    Stokes, Paul R A; Myers, Jim F; Kalk, Nicola J; Watson, Ben J; Erritzoe, David; Wilson, Sue J; Cunningham, Vincent J; Riano Barros, Daniela; Hammers, Alexander; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

    2014-10-01

    The inhibitory γ-aminobutyric acid (GABA) neurotransmitter system is associated with the regulation of normal cognitive functions and dysregulation has been reported in a number of neuropsychiatric disorders including anxiety disorders, schizophrenia and addictions. Investigating the role of GABA in both health and disease has been constrained by difficulties in measuring acute changes in synaptic GABA using neurochemical imaging. The aim of this study was to investigate whether acute increases in synaptic GABA are detectable in the living human brain using the inverse agonist GABA-benzodiazepine receptor (GABA-BZR) positron emission tomography (PET) tracer, [(11)C]Ro15-4513. We examined the effect of 15 mg oral tiagabine, which increases synaptic GABA by inhibiting the GAT1 GABA uptake transporter, on [(11)C]Ro15-4513 binding in 12 male participants using a paired, double blind, placebo-controlled protocol. Spectral analysis was used to examine synaptic α1 and extrasynaptic α5 GABA-BZR subtype availability in brain regions with high levels of [(11)C]Ro15-4513 binding. We also examined the test-retest reliability of α1 and a5-specific [(11)C]Ro15-4513 binding in a separate cohort of 4 participants using the same spectral analysis protocol. Tiagabine administration produced significant reductions in hippocampal, parahippocampal, amygdala and anterior cingulate synaptic α1 [(11)C]Ro15-4513 binding, and a trend significance reduction in the nucleus accumbens. These reductions were greater than test-retest reliability, indicating that they are not the result of chance observations. Our results suggest that acute increases in endogenous synaptic GABA are detectable in the living human brain using [(11)C]Ro15-4513 PET. These findings have potentially major implications for the investigation of GABA function in brain disorders and in the development of new treatments targeting this neurotransmitter system. PMID:24844747

  7. Amphetamine Decreases α2C-Adrenoceptor Binding of [11C]ORM-13070: A PET Study in the Primate Brain

    PubMed Central

    Hughes, Zoë A; Haaparanta-Solin, Merja; Stepanov, Vladimir; Nakao, Ryuji; Varnäs, Katarina; Varrone, Andrea; Arponen, Eveliina; Marjamäki, Päivi; Pohjanoksa, Katariina; Vuorilehto, Lauri; Babalola, Phebian A; Solin, Olof; Grimwood, Sarah; Sallinen, Jukka; Farde, Lars; Scheinin, Mika; Halldin, Christer

    2015-01-01

    Background: The neurotransmitter norepinephrine has been implicated in psychiatric and neurodegenerative disorders. Examination of synaptic norepinephrine concentrations in the living brain may be possible with positron emission tomography (PET), but has been hampered by the lack of suitable radioligands. Methods: We explored the use of the novel α2C-adrenoceptor antagonist PET tracer [11C]ORM-13070 for measurement of amphetamine-induced changes in synaptic norepinephrine. The effect of amphetamine on [11C]ORM-13070 binding was evaluated ex vivo in rat brain sections and in vivo with PET imaging in monkeys. Results: Microdialysis experiments confirmed amphetamine-induced elevations in rat striatal norepinephrine and dopamine concentrations. Regional [11C]ORM-13070 receptor binding was high in the striatum and low in the cerebellum. After injection of [11C]ORM-13070 in rats, mean striatal specific binding ratios, determined using cerebellum as a reference region, were 1.4±0.3 after vehicle pretreatment and 1.2±0.2 after amphetamine administration (0.3mg/kg, subcutaneous). Injection of [11C]ORM-13070 in non-human primates resulted in mean striatal binding potential (BP ND) estimates of 0.65±0.12 at baseline. Intravenous administration of amphetamine (0.5 and 1.0mg/kg, i.v.) reduced BP ND values by 31–50%. Amphetamine (0.3mg/kg, subcutaneous) increased extracellular norepinephrine (by 400%) and dopamine (by 270%) in rat striata. Conclusions: Together, these results indicate that [11C]ORM-13070 may be a useful tool for evaluation of synaptic norepinephrine concentrations in vivo. Future studies are required to further understand a potential contribution of dopamine to the amphetamine-induced effect. PMID:25522417

  8. The PET Radioligand 18F-FIMX Images and Quantifies Metabotropic Glutamate Receptor 1 in Proportion to the Regional Density of Its Gene Transcript in Human Brain

    PubMed Central

    Zanotti-Fregonara, Paolo; Xu, Rong; Zoghbi, Sami S.; Liow, Jeih-San; Fujita, Masahiro; Veronese, Mattia; Gladding, Robert L.; Rallis-Frutos, Denise; Hong, Jinsoo; Pike, Victor W.; Innis, Robert B.

    2016-01-01

    A recent study from our laboratory found that 18F-FIMX is an excellent PET radioligand for quantifying metabotropic glutamate receptor 1 (mGluR1) in monkey brain. This study evaluated the ability of 18F-FIMX to quantify mGluR1 in humans. A second goal was to use the relative density of mGluR1 gene transcripts in brain regions to estimate specific uptake and nondisplaceable uptake (VND) in each brain region. Methods After injection of 189 ± 3 MBq of 18F-FIMX, 12 healthy volunteers underwent a dynamic PET scan over 120 min. For 6 volunteers, images were acquired until 210 min. A metabolite-corrected arterial input function was measured from the radial artery. Four other subjects underwent whole-body scanning to estimate radiation exposure. Results 18F-FIMX uptake into the human brain was high (SUV = 4–6 in the cerebellum), peaked at about 10 min, and washed out rapidly. An unconstrained 2-tissue-compartment model fitted the data well, and distribution volume (VT) (mL·cm−3) values ranged from 1.5 in the caudate to 11 in the cerebellum. A 120-min scan provided stable VT values in all regions except the cerebellum, for which an acquisition time of at least 170 min was necessary. VT values in brain regions correlated well with mGluR1 transcript density, and the correlation suggested that VND of 18F-FIMX was quite low (0.5 mL·cm−3). This measure of VND in humans was similar to that from a receptor blocking study in monkeys, after correcting for differences in plasma protein binding. Similar to other 18F-labeled ligands, the effective dose was about 23 µSv/MBq. Conclusion 18F-FIMX can quantify mGluR1 in the human brain with a 120- to 170-min scan. Correlation of brain uptake with the relative density of mGluR1 transcript allows specific receptor binding of a radioligand to be quantified without injecting pharmacologic doses of a blocking agent. PMID:26514176

  9. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET

    PubMed Central

    Kuntner, Claudia; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Wanek, Thomas; Stundner, Gloria; Karch, Rudolf; Brauner, Rebecca; Meier, Martin; Ding, Xiaoqi; Müller, Markus; Löscher, Wolfgang; Langer, Oliver

    2013-01-01

    Purpose Overactivity of the multidrug efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) is believed to play an important role in resistance to central nervous system drug treatment. (R)-[11C]verapamil (VPM) PET can be used to measure the function of P-gp at the BBB, but low brain uptake of VPM hampers the mapping of regional differences in cerebral P-gp function and expression. The aim of this study was to evaluate the dose-response relationship of two potent P-gp inhibitors and to investigate if increased brain uptake of VPM mediated by P-gp inhibition can be used to assess regional differences in P-gp activity. Methods Two groups of Sprague-Dawley rats (n=12) underwent single VPM PET scans at 120 min after administration of different doses of the P-gp inhibitors tariquidar and elacridar. In an additional 6 rats, paired VPM PET scans were performed before and after administration of 3 mg/kg tariquidar. Results Inhibitor administration resulted in an up to 11-fold increase in VPM brain distribution volumes (DV) with ED50 values of 3.0±0.2 and 1.2±0.1 mg/kg for tariquidar and elacridar, respectively. In paired PET scans, 3 mg/kg tariquidar resulted in regionally different enhancement of brain activity distribution, with lowest DV in cerebellum and highest DV in thalamus. Conclusion Our data show that tariquidar and elacridar are able to increase VPM brain distribution in rat brain up to 11-fold over baseline at maximum effective doses, with elacridar being about 3 times more potent than tariquidar. Regional differences in tariquidar-induced modulation of VPM brain uptake point to regional differences in cerebral P-gp function and expression in rat brain. PMID:20016890

  10. SU-E-QI-03: Compartment Modeling of Dynamic Brain PET - The Effect of Scatter and Random Corrections On Parameter Errors

    SciTech Connect

    Häggström, I; Karlsson, M; Larsson, A; Schmidtlein, C

    2014-06-15

    Purpose: To investigate the effects of corrections for random and scattered coincidences on kinetic parameters in brain tumors, by using ten Monte Carlo (MC) simulated dynamic FLT-PET brain scans. Methods: The GATE MC software was used to simulate ten repetitions of a 1 hour dynamic FLT-PET scan of a voxelized head phantom. The phantom comprised six normal head tissues, plus inserted regions for blood and tumor tissue. Different time-activity-curves (TACs) for all eight tissue types were used in the simulation and were generated in Matlab using a 2-tissue model with preset parameter values (K1,k2,k3,k4,Va,Ki). The PET data was reconstructed into 28 frames by both ordered-subset expectation maximization (OSEM) and 3D filtered back-projection (3DFBP). Five image sets were reconstructed, all with normalization and different additional corrections C (A=attenuation, R=random, S=scatter): Trues (AC), trues+randoms (ARC), trues+scatters (ASC), total counts (ARSC) and total counts (AC). Corrections for randoms and scatters were based on real random and scatter sinograms that were back-projected, blurred and then forward projected and scaled to match the real counts. Weighted non-linearleast- squares fitting of TACs from the blood and tumor regions was used to obtain parameter estimates. Results: The bias was not significantly different for trues (AC), trues+randoms (ARC), trues+scatters (ASC) and total counts (ARSC) for either 3DFBP or OSEM (p<0.05). Total counts with only AC stood out however, with an up to 160% larger bias. In general, there was no difference in bias found between 3DFBP and OSEM, except in parameter Va and Ki. Conclusion: According to our results, the methodology of correcting the PET data for randoms and scatters performed well for the dynamic images where frames have much lower counts compared to static images. Generally, no bias was introduced by the corrections and their importance was emphasized since omitting them increased bias extensively.

  11. A simple system for remote processing and delivery of H{sub 2}[{sup 15}O] produced from a N{sub 2}/H{sub 2} target

    SciTech Connect

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.L.; Wolf, A.P.

    1993-12-31

    The N{sub 2} + H{sub 2} target can produce more than enough H{sub 2}[{sup 15}O] to meet the demands of any PET imaging facility. We have shown that the radiotracer can be transported across 300 feet of tubing without significant loss of activity, using fast tows of target gas. Thus, there is no need to maintain an extraneous chemical Processing station at the PET imaging facility. A simple remotely operated system is reported that performs the three step operation for H{sub 2}[{sup 15}O] delivery at the PET imaging facility: collection of the radiotracer in water; removal of ammonia from the preparation and delivery of the radiotracer to the injection syringe. The system can process and make available for injection 100 mCi of H{sub 2}[{sup 15}O]. The machine is easily prepped for subsequent deliveries. So that additional doses of radiotracer can be made available within 12 minutes. A general syringe loading device with remote hydraulic injector is that is compatible for use with any H{sub 2}[{sup 15}O] radiotracer processing station. The device allows for direct measurement of syringe dose while filling, and for easy, as well as safe transfer of the injection syringe assembly to a delivery cart that houses the remote hydraulic injector. The injection syringe is never handled directly during transport nor during injection except, to connect it to the intravenous line, thus minimizing radiation exposure to personnel.

  12. Positron emission tomography/magnetic resonance hybrid scanner imaging of cerebral blood flow using 15O-water positron emission tomography and arterial spin labeling magnetic resonance imaging in newborn piglets

    PubMed Central

    Andersen, Julie B; Henning, William S; Lindberg, Ulrich; Ladefoged, Claes N; Højgaard, Liselotte; Greisen, Gorm; Law, Ian

    2015-01-01

    Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic–ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous 15O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq 15O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% (P<0.0001) and −0.7% (P=0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% (P=0.001) and 24% (P=0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq 15O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion. PMID:26058699

  13. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain

    PubMed Central

    Polis, Ingeborgh; Neyt, Sara; Kersemans, Ken; Dobbeleir, Andre; Saunders, Jimmy; Goethals, Ingeborg; Peremans, Kathelijne; De Vos, Filip

    2016-01-01

    This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID:26859850

  14. Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

    PubMed

    Shih, Jui-Hu; Ma, Kuo-Hsing; Chen, Chien-Fu F; Cheng, Cheng-Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng-Yann; Yeh, Ming-Kung; Li, I-Hsun

    2016-01-01

    The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA. PMID:26612383

  15. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain.

    PubMed

    Van Laeken, Nick; Taylor, Olivia; Polis, Ingeborgh; Neyt, Sara; Kersemans, Ken; Dobbeleir, Andre; Saunders, Jimmy; Goethals, Ingeborg; Peremans, Kathelijne; De Vos, Filip

    2016-01-01

    This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID:26859850

  16. Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment.

    PubMed

    Milak, Matthew S; Parsey, Ramin V; Lee, Leilani; Oquendo, Maria A; Olvet, Doreen M; Eipper, Francoise; Malone, Kevin; Mann, J John

    2009-07-15

    In order to test the hypotheses that pretreatment metabolic activity in the midbrain and the rostral anterior cingulate may predict remission in response to medications enhancing monoaminergic transmission, we compared relative regional cerebral metabolic rate of glucose (rCMRglu) using positron emission tomography (PET) in medication-free patients with major depression who remitted after 3 months of monoaminergic medication, with non-remitters on the same treatment. [(18)F]-FDG PET was conducted in a group of 33 drug-free DSM-IV major depression subjects prior to antidepressant treatment. Patients were prescribed paroxetine initially (61%) unless they had failed paroxetine previously. Treatment was then managed by the subjects' own physician with 91% receiving a selective serotonin reuptake inhibitor and 78% another non-selective monoamine reuptake inhibitor during the 3 months of treatment. Voxel-based parametric brain maps of remitters were compared with maps of non-remitters using SPM2. Remission was defined as a >50% decrease in and a final score of brain region (with global maxima in the midbrain, cluster level P=0.013, corrected for multiple comparison (CMC)), prior to treatment, compared with non-remitters to 3 months of community-based monoaminergic antidepressant treatment. Degree of improvement correlated with pretreatment midbrain activity. Pretreatment clinical picture and intensity of treatment did not distinguish remitters. No other area of the brain showed a significant difference between remitters and non-remitters even with CMC completely disabled. Lower relative regional brain activity in the region of monoaminergic nuclei prior to treatment predicts remission in response to 3 months of antidepressant treatment, despite no clinical differences at baseline and no difference in treatment intensity. Brain imaging is a

  17. Effects of neonatal amygdala or hippocampus lesions on resting brain metabolism in the macaque monkey: A microPET imaging study

    PubMed Central

    Machado, Christopher J.; Snyder, Abraham Z.; Cherry, Simon R.; Lavenex, Pierre; Amaral, David G.

    2007-01-01

    Longitudinal analysis of animals with neonatal brain lesions enables the evaluation of behavioral changes during multiple stages of development. Interpretation of such changes, however, carries the caveat that permanent neural injury also yields morphological and neurochemical reorganization elsewhere in the brain that may lead either to functional compensation or to exacerbation of behavioral alterations. We have measured the long-term effects of selective neonatal brain damage on resting cerebral glucose metabolism in nonhuman primates. Sixteen rhesus monkeys (Macaca mulatta) received neurotoxic lesions of either the amygdala (n = 8) or hippocampus (n = 8) when they were 2-weeks-old. Four years later, these animals, along with age- and experience-matched sham-operated control animals (n = 8), were studied with high-resolution positron emission tomography (microPET) and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) to detect areas of altered metabolism. The groups were compared using an anatomically-based region of interest analysis. Relative to controls, amygdala-lesioned animals displayed hypometabolism in three frontal lobe regions, as well as in the neostriatum and hippocampus. Hypermetabolism was also evident in the cerebellum of amygdala-lesioned animals. Hippocampal-lesioned animals only showed hypometabolism in the retrosplenial cortex. These results indicate that neonatal amygdala and hippocampus lesions induce very different patterns of long-lasting metabolic changes in distant brain regions. These observations raise the possibility that behavioral alterations in animals with neonatal lesions may be due to the intended damage, to consequent brain reorganization or to a combination of both factors. PMID:17964814

  18. Professor Pet.

    ERIC Educational Resources Information Center

    Pet Information Bureau, New York, NY.

    This manual outlines ways in which observation and care of classroom pet animals may be used to enrich the education of elementary school children. Part one deals with the benefits of having pets in the classroom. Part two illustrates ways in which pets can serve as valuable teaching tools and gives examples of lessons in which the use of pets can…

  19. Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: Importance of partial volume correction

    SciTech Connect

    Hatazawa, J.; Hatano, K.; Ishiwata, K.; Itoh, M.; Ido, T.; Kawashima, K.; Meguro, K.; Watanuki, S.; Seo, S. )

    1991-04-01

    Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

  20. 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. PMID:26644334

  1. PET Imaging with [(18)F]FSPG Evidences the Role of System xc(-) on Brain Inflammation Following Cerebral Ischemia in Rats.

    PubMed

    Domercq, Maria; Szczupak, Boguslaw; Gejo, Jon; Gómez-Vallejo, Vanessa; Padro, Daniel; Gona, Kiran Babu; Dollé, Frédéric; Higuchi, Makoto; Matute, Carlos; Llop, Jordi; Martín, Abraham

    2016-01-01

    In vivo Positron Emission Tomography (PET) imaging of the cystine-glutamate antiporter (system xc(-)) activity with [(18)F]FSPG is meant to be an attractive tool for the diagnosis and therapy evaluation of brain diseases. However, the role of system xc(-) in cerebral ischemia and its involvement in inflammatory reaction has been scarcely explored. In this work, we report the longitudinal investigation of the neuroinflammatory process following transient middle cerebral artery occlusion (MCAO) in rats using PET with [(18)F]FSPG and the translocator protein (TSPO) ligand [(18)F]DPA-714. In the ischemic territory, [(18)F]FSPG showed a progressive binding increase that peaked at days 3 to 7 and was followed by a progressive decrease from days 14 to 28 after reperfusion. In contrast, [(18)F]DPA-714 evidenced maximum binding uptake values over day 7 after reperfusion. Ex vivo immnunohistochemistry confirmed the up-regulation of system xc(-) in microglial cells and marginally in astrocytes. Inhibition of system xc(-) with sulfasalazine and S-4-CPG resulted in increased arginase (anti-inflammatory M2 marker) expression at day 7 after ischemia, together with a decrease in TSPO and microglial M1 proinflammatory markers (CCL2, TNF and iNOS) expression. Taken together, these results suggest that system xc(-) plays a key role in the inflammatory reaction underlying experimental stroke. PMID:27570548

  2. PET Imaging with [18F]FSPG Evidences the Role of System xc- on Brain Inflammation Following Cerebral Ischemia in Rats

    PubMed Central

    Domercq, Maria; Szczupak, Boguslaw; Gejo, Jon; Gómez-Vallejo, Vanessa; Padro, Daniel; Gona, Kiran Babu; Dollé, Frédéric; Higuchi, Makoto; Matute, Carlos; Llop, Jordi; Martín, Abraham

    2016-01-01

    In vivo Positron Emission Tomography (PET) imaging of the cystine-glutamate antiporter (system xc-) activity with [18F]FSPG is meant to be an attractive tool for the diagnosis and therapy evaluation of brain diseases. However, the role of system xc- in cerebral ischemia and its involvement in inflammatory reaction has been scarcely explored. In this work, we report the longitudinal investigation of the neuroinflammatory process following transient middle cerebral artery occlusion (MCAO) in rats using PET with [18F]FSPG and the translocator protein (TSPO) ligand [18F]DPA-714. In the ischemic territory, [18F]FSPG showed a progressive binding increase that peaked at days 3 to 7 and was followed by a progressive decrease from days 14 to 28 after reperfusion. In contrast, [18F]DPA-714 evidenced maximum binding uptake values over day 7 after reperfusion. Ex vivo immnunohistochemistry confirmed the up-regulation of system xc- in microglial cells and marginally in astrocytes. Inhibition of system xc- with sulfasalazine and S-4-CPG resulted in increased arginase (anti-inflammatory M2 marker) expression at day 7 after ischemia, together with a decrease in TSPO and microglial M1 proinflammatory markers (CCL2, TNF and iNOS) expression. Taken together, these results suggest that system xc- plays a key role in the inflammatory reaction underlying experimental stroke. PMID:27570548

  3. Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.

    PubMed

    Jovanovic, Hristina; Kocoska-Maras, Ljiljana; Rådestad, Angelique Flöter; Halldin, Christer; Borg, Jacqueline; Hirschberg, Angelica Lindén; Nordström, Anna-Lena

    2015-02-01

    Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 μg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders. PMID:25462800

  4. Fast and accurate water content and T2* mapping in brain tumours localised with FET-PET

    NASA Astrophysics Data System (ADS)

    Oros-Peusquens, A.-M.; Keil, F.; Langen, K. J.; Herzog, H.; Stoffels, G.; Weiss, C.; Shah, N. J.

    2014-01-01

    The availability of combined MR-PET scanners opens new opportunities for the characterisation of tumour environment. In this study, water content and relaxation properties of glioblastoma were investigated in five patients using advanced MRI. The region containing metabolically active tumour tissue was defined by simultaneously measured FET-PET uptake. The mean value of water content in tumour tissue - obtained noninvasively with high precision and accuracy for the first time - amounted to 84.5%, similar to the value for normal grey matter. Constancy of water content contrasted with a large variability of T2* values in tumour tissue, qualitatively related to the magnetic inhomogeneity of tissue created by blood vessels and/or microbleeds. The quantitative MRI protocol takes 71/2 > min of measurement time and is proposed for extended clinical use.

  5. Novel Histone Deacetylase Class IIa Selective Substrate Radiotracers for PET Imaging of Epigenetic Regulation in the Brain

    PubMed Central

    Bonomi, Robin; Mukhopadhyay, Uday; Shavrin, Aleksandr; Yeh, Hsien-Hsien; Majhi, Anjoy; Dewage, Sajeewa W.; Najjar, Amer; Lu, Xin; Cisneros, G. Andrés; Tong, William P.; Alauddin, Mian M.; Liu, Ren-Shuan; Mangner, Thomas J.; Turkman, Nashaat; Gelovani, Juri G.

    2015-01-01

    Histone deacetylases (HDAC’s) became increasingly important targets for therapy of various diseases, resulting in a pressing need to develop HDAC class- and isoform-selective inhibitors. Class IIa deacetylases possess only minimal deacetylase activity against acetylated histones, but have several other client proteins as substrates through which they participate in epigenetic regulation. Herein, we report the radiosyntheses of the second generation of HDAC class IIa–specific radiotracers: 6-(di-fluoroacetamido)-1-hexanoicanilide (DFAHA) and 6-(tri-fluoroacetamido)-1-hexanoicanilide ([18F]-TFAHA). The selectivity of these radiotracer substrates to HDAC class IIa enzymes was assessed in vitro, in a panel of recombinant HDACs, and in vivo using PET/CT imaging in rats. [18F]TFAHA showed significantly higher selectivity for HDAC class IIa enzymes, as compared to [18F]DFAHA and previously reported [18F]FAHA. PET imaging with [18F]TFAHA can be used to visualize and quantify spatial distribution and magnitude of HDAC class IIa expression-activity in different organs and tissues in vivo. Furthermore, PET imaging with [18F]TFAHA may advance the understanding of HDACs class IIa mediated epigenetic regulation of normal and pathophysiological processes, and facilitate the development of novel HDAC class IIa-specific inhibitors for therapy of different diseases. PMID:26244761

  6. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    PubMed

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage. PMID:24285318

  7. Awake Nonhuman Primate Brain PET Imaging with Minimal Head Restraint: Evaluation of GABAA Benzodiazepine Binding with [11C]Flumazenil in Awake and Anesthetized Animals

    PubMed Central

    Sandiego, Christine M.; Jin, Xiao; Mulnix, Tim; Fowles, Krista; Labaree, David; Ropchan, Jim; Huang, Yiyun; Cosgrove, Kelly; Castner, Stacy A.; Williams, Graham V.; Wells, Lisa; Rabiner, Eugenii A.; Carson, Richard E.

    2013-01-01

    Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational research approaches in humans. However, the majority of NHP studies are conducted under anesthesia, which affects the interpretability of receptor binding measures. The aims of this study are to develop awake NHP imaging with minimal head restraint and to compare in vivo binding of GABAA-benzodiazepine radiotracer [11C]flumazenil under anesthetized and awake conditions. We hypothesized that [11C]flumazenil binding potential (BPND) would be higher in isoflurane-anesthetized monkeys. Methods The Focus-220 small animal PET scanner was fitted to a mechanical device that raised and tilted the scanner 45° while the awake NHP was tilted back 35° in a custom chair for optimal brain positioning. This required acclimation of the animals to the chair, touch-screen tasks, i.v. catheter insertion, and tilting. For PET studies, the bolus plus constant infusion (B/I) method was used for [11C]flumazenil administration. Two rhesus monkeys were scanned under the awake (n=6 scans) and isoflurane-anesthetized (n=4 scans) conditions. The Vicra infrared camera was used to track head motion during PET scans. Under the awake condition, emission and head motion-tracking data were acquired for 40-75 min post-injection. Anesthetized monkeys were scanned for 90 min. Cortisol measurements were acquired during awake and anesthetized scans. Equilibrium analysis was used for both the anesthetized (n=4) and awake (n=5) datasets to compute mean BPND images in NHP template space, using the pons as a reference region. Percent change per min (%Δ/min) in radioactivity concentration was calculated in high and low binding regions to assess the quality of equilibrium. Results The monkeys acclimated to procedures in the NHP chair necessary to perform awake PET imaging. Image quality was comparable between awake and anesthetized conditions. The relationship between awake and anesthetized values was BPND(awake)=0.94BPND

  8. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  9. Dose fractionation and single subject studies in PET

    NASA Astrophysics Data System (ADS)

    Balakrishnan, Karthikayan

    Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals

  10. The Compression Flow as a Measure to Estimate the Brain Connectivity Changes in Resting State fMRI and 18FDG-PET Alzheimer's Disease Connectomes

    PubMed Central

    Zippo, Antonio G.; Castiglioni, Isabella; Borsa, Virginia M.; Biella, Gabriele E. M.

    2015-01-01

    The human brain appears organized in compartments characterized by seemingly specific functional purposes on many spatial scales. A complementary functional state binds information from specialized districts to return what is called integrated information. These fundamental network dynamics undergoes to severe disarrays in diverse degenerative conditions such as Alzheimer's Diseases (AD). The AD represents a multifarious syndrome characterized by structural, functional, and metabolic landmarks. In particular, in the early stages of AD, adaptive functional modifications of the brain networks mislead initial diagnoses because cognitive abilities may result indiscernible from normal subjects. As a matter of facts, current measures of functional integration fail to catch significant differences among normal, mild cognitive impairment (MCI) and even AD subjects. The aim of this work is to introduce a new topological feature called Compression Flow (CF) to finely estimate the extent of the functional integration in the brain networks. The method uses a Monte Carlo-like estimation of the information integration flows returning the compression ratio between the size of the injected information and the size of the condensed information within the network. We analyzed the resting state connectomes of 75 subjects of the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI) repository. Our analyses are focused on the 18FGD-PET and functional MRI (fMRI) acquisitions in several clinical screening conditions. Results indicated that CF effectively discriminate MCI, AD and normal subjects by showing a significant decrease of the functional integration in the AD and MCI brain connectomes. This result did not emerge by using a set of common complex network statistics. Furthermore, CF was best correlated with individual clinical scoring scales. In conclusion, we presented a novel measure to quantify the functional integration that resulted efficient to discriminate different stages of