Marie-claude Asselin - Academia.edu (original) (raw)
Papers by Marie-claude Asselin
Stem cell reports, Jan 13, 2018
Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and ... more Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and disease. We reproducibly differentiated three genetically distinct wild-type hPSC lines to kidney precursors that underwent rudimentary morphogenesis in vitro. They expressed nephron and collecting duct lineage marker genes, several of which are mutated in human kidney disease. Lentiviral-transduced hPSCs expressing reporter genes differentiated similarly to controls in vitro. Kidney progenitors were subcutaneously implanted into immunodeficient mice. By 12 weeks, they formed organ-like masses detectable by bioluminescence imaging. Implants included perfused glomeruli containing human capillaries, podocytes with regions of mature basement membrane, and mesangial cells. After intravenous injection of fluorescent low-molecular-weight dextran, signal was detected in tubules, demonstrating uptake from glomerular filtrate. Thus, we have developed methods to trace hPSC-derived kidney precursor...
Clinical lung cancer, May 11, 2017
There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherap... more There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non-small-cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. Blood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)-1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04-7.93; P < .001) was the only significant survival covariate. Of routinely collected ...
JNCI: Journal of the National Cancer Institute
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in trea... more Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials. Radiotherapy dose painting strategies based on hypoxia imaging require careful refinement prior to clinical investigation. This review will summarize the role of hypoxia, highlight the potential of hypoxia as a therapeutic target, and outline past and ongoing hypoxia-targeted therapy trials in NSCLC. Evidence supporting radiotherapy dose painting based on hypoxia imaging will be critically appraised. Carefully selected hypoxia biomarkers suitable for integration within future NSCLC hypoxia-targeted therapy trials will be examined. Research gaps will be identified to guide future investigation. Although this review will focus on NSCLC hypoxia, more general discussions (eg, obstacles of hypoxia biomarker research and developing a framework for future hypoxia trials) are applicable to other tumor sites.
Critical Reviews in Oncology/Hematology, 2015
Pancreatic ductal adenocarcinoma is known for its poor prognosis. Since the development of comput... more Pancreatic ductal adenocarcinoma is known for its poor prognosis. Since the development of computerized tomography, magnetic resonance and endoscopic ultrasound, novel imaging techniques have struggled to get established in the management of patients diagnosed with pancreatic adenocarcinoma for several reasons. Thus, imaging assessment of pancreatic cancer remains a field with scope for further improvement. In contrast to cross-sectional anatomical imaging methods, molecular imaging modalities such as positron emission tomography (PET) can provide information on tumour function. Particularly, tumour proliferation may be assessed by measurement of intracellular thymidine kinase 1 (TK1) activity level using thymidine analogues radiolabelled with a positron emitter for use with PET. This approach, has been widely explored with [(18)F]-fluoro-3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxy-3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-l-fluorothymidine ((18)F-FLT) PET. This manuscript reviews the rationale and physiology behind (18)F-FLT PET imaging, with special focus on pancreatic cancer and other gastrointestinal malignancies. Potential benefit and challenges of this imaging technique for diagnosis, staging and assessment of treatment response in abdominal malignancies are discussed.
![Research paper thumbnail of Equilibration of 6-[18F]fluoro-L-m-tyrosine between plasma and erythrocytes](https://attachments.academia-assets.com/67139571/thumbnails/1.jpg)
](Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2000
Intracranial or intraventricular blood pools have been suggested as noninvasive sources of an inp... more Intracranial or intraventricular blood pools have been suggested as noninvasive sources of an input function for quantitative PET. These techniques measure the concentration of the tracer in whole blood, but the concentration in plasma depends on the equilibration of the tracer between plasma and erythrocytes. FDG, 6-[18F]fluoro-L-m-tyrosine (FmT), or its major metabolite, 6-[18F]fluoro-3-hydroxyphenylacetic acid (FHPAA), was added to blood samples obtained from healthy fasting volunteers along with radioiodinated human serum albumin (RIHSA). Samples were incubated at 37 degrees C for times between 10 s and 2 h and then plunged into an ice bath and centrifuged. Whole blood and plasma were counted for 18F and 125I activities. The resulting time courses were fit to successively more complex models, evaluated using an F test. All radioactivity associated with RIHSA remained in the plasma, whereas FDG equilibrated instantaneously between plasma and erythrocytes. FmT took about 1 h to eq...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1999
As clinical PET becomes increasingly available, quantitative methods that are feasible in busy cl... more As clinical PET becomes increasingly available, quantitative methods that are feasible in busy clinical settings are becoming necessary. We investigated the use of intracranial blood pools as sources of an input function for quantitative PET. We studied 25 patients after the intravenous injection of [18F]6-fluoro-L-m-tyrosine and compared sampled blood time-activity curves with those obtained in small regions of interest (ROIs) defined in the blood pools visible in the PET images. Because of the comparatively large dimensions of the blood pool at the confluence of the superior sagittal, straight and transverse sinuses, a venous ROI input function was chosen for further analysis. We applied simple corrections to the ROI-derived time-activity curves, deriving expressions for partial volume, spillover and partition of tracer between plasma and red blood cells. The results of graphic and compartmental analysis using both sampled [Cs(t)] and ROI [Cr(t)] venous input functions for each pa...
2007 IEEE Nuclear Science Symposium Conference Record, 2007
Page 1. Patient-Specific Noise-Equivalent-Counts from Repeated, Dose Varying [O-15]H2O PET Scans ... more Page 1. Patient-Specific Noise-Equivalent-Counts from Repeated, Dose Varying [O-15]H2O PET Scans Matthew D. Walker, Student Member, IEEE, Julian C. Matthews, Marie-Claude Asselin, Azeem Saleem, Pat Price and Terry Jones ...
IEEE Nuclear Science Symposuim & Medical Imaging Conference, 2010
Patient motion during PET scans introduces errors in the attenuation correction and image blurrin... more Patient motion during PET scans introduces errors in the attenuation correction and image blurring leading to false changes in regional radioactivity concentrations. However, the potential effect that motion has on simulation-based scatter correction is not fully appreciated. Specifically for tracers with high uptake close to the edge of head (e.g. scalp and nose) as observed with [ 11 C]Verapamil, mismatches between transmission and emission data can lead to significant quantification errors and image artefacts due to over scatter correction. These errors are linked with unusually high values in the scatter scaling factors (SSF) returned during the single scatter simulation process implemented in the HRRT image reconstruction. Reconstruction of µ-map with TXTV (an alternative µ-map reconstruction using non-linear filtering rather than brain segmentation and scatter correction of the transmission data) was found to improve the scatter simulation results for [ 11 C]Verapamil and [ 18 F]FDG. The errors from patient motion were characterised and quantified through simulations by applying realistic transformations to the attenuation map (µmap). This generated inconsistencies between the emission and transmission data, and introduced large over-corrections of scatter similar to some cases observed with [ 11 C]Verapamil. Automated Image Registration (AIR) based motion correction was also implemented, and found to remove the artifact and recover quantification in dynamic studies after aligning all the PET images to a common reference space.
2008 IEEE Nuclear Science Symposium Conference Record, 2008
... Optimizing Dose in 3D [15 0O]H 20 PET Scans Matthew D. Walker, Student Member, IEEE, Julian C... more ... Optimizing Dose in 3D [15 0O]H 20 PET Scans Matthew D. Walker, Student Member, IEEE, Julian C. Matthews, Marie-Claude Asselin, Charles C. Watson, Senior Member; IEEE, Azeem Saleem,Natalie Chamley, Peter J. Julyan, Patricia M. Price and Terry Jones ...
Molecular Imaging and Biology, 2014
This study was conducted to directly compare the high-resolution research tomograph (HRRT) (high-... more This study was conducted to directly compare the high-resolution research tomograph (HRRT) (high-resolution brain) and HR+ (standard whole-body) positron emission tomography (PET) only scanners for quantitative brain studies using three tracers with vastly different tracer distributions. Healthy volunteers underwent successive scans on HR+ and HRRT scanners (in random order) using either (R)-[(11)C]verapamil (n = 6), [(11)C]raclopride (n = 7) or [(11)C]flumazenil (n = 7). For all tracers, metabolite-corrected plasma-input functions were generated. After resolution matching, HRRT-derived kinetic parameter values correlated well with those of HR+ for all tracers (intraclass correlation coefficients ≥0.78), having a good absolute interscanner test-retest variability (≤15 %). However, systematic differences can be seen for HRRT-derived kinetic parameter values (range -13 to +15 %). Quantification of kinetic parameters based on plasma-input models leads to comparable results when spatial resolution between HRRT and HR+ data is matched. When using reference-tissue models, differences remain that are likely caused by differences in attenuation and scatter corrections and/or image reconstruction.
Neurology, Jan 7, 2014
To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the ... more To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[(11)C]verapamil (VPM)-PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function. Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- and postsurgery. Patients were followed up for a median of 6 years (range 4-7) after surgery. Pgp immunoreactivity in surgically resected hippocampal specimens was determined with immunohistochemistry. Optimal surgical outcome, defined as seizure freedom and withdrawal of antiepileptic drugs, was associated with higher temporal lobe Pgp function before surgery, higher Pgp-positive staining in surgically resected hippocampal specimens, and reduction in global Pgp function postoperatively, compared with nonoptimal surgery outcome. The data...
![Research paper thumbnail of Parametric mapping of [C-11]FLB457 binding using spectral analysis](https://attachments.academia-assets.com/67139558/thumbnails/1.jpg)
](IEEE Nuclear Science Symposuim & Medical Imaging Conference, 2010
Page 1. Comparison of Methods for Quantification of rCBF on the HRRT PET Scanner Using [ 15 O]H2O... more Page 1. Comparison of Methods for Quantification of rCBF on the HRRT PET Scanner Using [ 15 O]H2O Matthew D. Walker, Member, IEEE, Maria Feldmann, Jose M. Anton-Rodriguez, Member, IEEE, Shaonan Wang, Julian ...
Schizophrenia Research, 2008
Physics in Medicine and Biology, 2002
Physiological quantification of dynamic PET data requires the determination of an input function,... more Physiological quantification of dynamic PET data requires the determination of an input function, preferably from plasma. A compartmental model relating a parent radiotracer, its radiolabelled metabolites and their exchange between plasma and erythrocytes is presented. This model allows for the time course of radioactivity measured in whole blood to be transformed into the time course of the radiotracer in plasma. The utility of this approach is illustrated with blood data collected on 30 human subjects injected with 6-[18F]fluoro-L-meta-tyrosine (FmT), a pre-synaptic dopaminergic radiotracer. A three-compartment four-parameter model is shown to yield significantly better fits to the blood data than related lower and higher order models. This model is found to be robust to measurement noise, and yet sensitive to metabolic changes induced by pretreatment with carbidopa. For FmT, the between-subject variations are shown to be small enough to warrant the use of a population-based correction; tissue time-activity curves were simulated to verify that this correction does not significantly affect the precision and accuracy of the derived rate constants. The unified blood model can be adapted for radiotracers other than FmT as long as the blood partition ratio of the parent radiotracer differs from that of its metabolites and/or the rate at which they equilibrate between plasma and erythrocytes is different.
Physics in Medicine and Biology, 2004
A non-invasive alternative to arterial blood sampling for the generation of a blood input functio... more A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[18F]fluoro-L-DOPA and one subject injected with [11C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 +/- 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest.
Stem cell reports, Jan 13, 2018
Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and ... more Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and disease. We reproducibly differentiated three genetically distinct wild-type hPSC lines to kidney precursors that underwent rudimentary morphogenesis in vitro. They expressed nephron and collecting duct lineage marker genes, several of which are mutated in human kidney disease. Lentiviral-transduced hPSCs expressing reporter genes differentiated similarly to controls in vitro. Kidney progenitors were subcutaneously implanted into immunodeficient mice. By 12 weeks, they formed organ-like masses detectable by bioluminescence imaging. Implants included perfused glomeruli containing human capillaries, podocytes with regions of mature basement membrane, and mesangial cells. After intravenous injection of fluorescent low-molecular-weight dextran, signal was detected in tubules, demonstrating uptake from glomerular filtrate. Thus, we have developed methods to trace hPSC-derived kidney precursor...
Clinical lung cancer, May 11, 2017
There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherap... more There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non-small-cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. Blood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)-1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04-7.93; P < .001) was the only significant survival covariate. Of routinely collected ...
JNCI: Journal of the National Cancer Institute
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in trea... more Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials. Radiotherapy dose painting strategies based on hypoxia imaging require careful refinement prior to clinical investigation. This review will summarize the role of hypoxia, highlight the potential of hypoxia as a therapeutic target, and outline past and ongoing hypoxia-targeted therapy trials in NSCLC. Evidence supporting radiotherapy dose painting based on hypoxia imaging will be critically appraised. Carefully selected hypoxia biomarkers suitable for integration within future NSCLC hypoxia-targeted therapy trials will be examined. Research gaps will be identified to guide future investigation. Although this review will focus on NSCLC hypoxia, more general discussions (eg, obstacles of hypoxia biomarker research and developing a framework for future hypoxia trials) are applicable to other tumor sites.
Critical Reviews in Oncology/Hematology, 2015
Pancreatic ductal adenocarcinoma is known for its poor prognosis. Since the development of comput... more Pancreatic ductal adenocarcinoma is known for its poor prognosis. Since the development of computerized tomography, magnetic resonance and endoscopic ultrasound, novel imaging techniques have struggled to get established in the management of patients diagnosed with pancreatic adenocarcinoma for several reasons. Thus, imaging assessment of pancreatic cancer remains a field with scope for further improvement. In contrast to cross-sectional anatomical imaging methods, molecular imaging modalities such as positron emission tomography (PET) can provide information on tumour function. Particularly, tumour proliferation may be assessed by measurement of intracellular thymidine kinase 1 (TK1) activity level using thymidine analogues radiolabelled with a positron emitter for use with PET. This approach, has been widely explored with [(18)F]-fluoro-3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxy-3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-l-fluorothymidine ((18)F-FLT) PET. This manuscript reviews the rationale and physiology behind (18)F-FLT PET imaging, with special focus on pancreatic cancer and other gastrointestinal malignancies. Potential benefit and challenges of this imaging technique for diagnosis, staging and assessment of treatment response in abdominal malignancies are discussed.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2000
Intracranial or intraventricular blood pools have been suggested as noninvasive sources of an inp... more Intracranial or intraventricular blood pools have been suggested as noninvasive sources of an input function for quantitative PET. These techniques measure the concentration of the tracer in whole blood, but the concentration in plasma depends on the equilibration of the tracer between plasma and erythrocytes. FDG, 6-[18F]fluoro-L-m-tyrosine (FmT), or its major metabolite, 6-[18F]fluoro-3-hydroxyphenylacetic acid (FHPAA), was added to blood samples obtained from healthy fasting volunteers along with radioiodinated human serum albumin (RIHSA). Samples were incubated at 37 degrees C for times between 10 s and 2 h and then plunged into an ice bath and centrifuged. Whole blood and plasma were counted for 18F and 125I activities. The resulting time courses were fit to successively more complex models, evaluated using an F test. All radioactivity associated with RIHSA remained in the plasma, whereas FDG equilibrated instantaneously between plasma and erythrocytes. FmT took about 1 h to eq...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1999
As clinical PET becomes increasingly available, quantitative methods that are feasible in busy cl... more As clinical PET becomes increasingly available, quantitative methods that are feasible in busy clinical settings are becoming necessary. We investigated the use of intracranial blood pools as sources of an input function for quantitative PET. We studied 25 patients after the intravenous injection of [18F]6-fluoro-L-m-tyrosine and compared sampled blood time-activity curves with those obtained in small regions of interest (ROIs) defined in the blood pools visible in the PET images. Because of the comparatively large dimensions of the blood pool at the confluence of the superior sagittal, straight and transverse sinuses, a venous ROI input function was chosen for further analysis. We applied simple corrections to the ROI-derived time-activity curves, deriving expressions for partial volume, spillover and partition of tracer between plasma and red blood cells. The results of graphic and compartmental analysis using both sampled [Cs(t)] and ROI [Cr(t)] venous input functions for each pa...
2007 IEEE Nuclear Science Symposium Conference Record, 2007
Page 1. Patient-Specific Noise-Equivalent-Counts from Repeated, Dose Varying [O-15]H2O PET Scans ... more Page 1. Patient-Specific Noise-Equivalent-Counts from Repeated, Dose Varying [O-15]H2O PET Scans Matthew D. Walker, Student Member, IEEE, Julian C. Matthews, Marie-Claude Asselin, Azeem Saleem, Pat Price and Terry Jones ...
IEEE Nuclear Science Symposuim & Medical Imaging Conference, 2010
Patient motion during PET scans introduces errors in the attenuation correction and image blurrin... more Patient motion during PET scans introduces errors in the attenuation correction and image blurring leading to false changes in regional radioactivity concentrations. However, the potential effect that motion has on simulation-based scatter correction is not fully appreciated. Specifically for tracers with high uptake close to the edge of head (e.g. scalp and nose) as observed with [ 11 C]Verapamil, mismatches between transmission and emission data can lead to significant quantification errors and image artefacts due to over scatter correction. These errors are linked with unusually high values in the scatter scaling factors (SSF) returned during the single scatter simulation process implemented in the HRRT image reconstruction. Reconstruction of µ-map with TXTV (an alternative µ-map reconstruction using non-linear filtering rather than brain segmentation and scatter correction of the transmission data) was found to improve the scatter simulation results for [ 11 C]Verapamil and [ 18 F]FDG. The errors from patient motion were characterised and quantified through simulations by applying realistic transformations to the attenuation map (µmap). This generated inconsistencies between the emission and transmission data, and introduced large over-corrections of scatter similar to some cases observed with [ 11 C]Verapamil. Automated Image Registration (AIR) based motion correction was also implemented, and found to remove the artifact and recover quantification in dynamic studies after aligning all the PET images to a common reference space.
2008 IEEE Nuclear Science Symposium Conference Record, 2008
... Optimizing Dose in 3D [15 0O]H 20 PET Scans Matthew D. Walker, Student Member, IEEE, Julian C... more ... Optimizing Dose in 3D [15 0O]H 20 PET Scans Matthew D. Walker, Student Member, IEEE, Julian C. Matthews, Marie-Claude Asselin, Charles C. Watson, Senior Member; IEEE, Azeem Saleem,Natalie Chamley, Peter J. Julyan, Patricia M. Price and Terry Jones ...
Molecular Imaging and Biology, 2014
This study was conducted to directly compare the high-resolution research tomograph (HRRT) (high-... more This study was conducted to directly compare the high-resolution research tomograph (HRRT) (high-resolution brain) and HR+ (standard whole-body) positron emission tomography (PET) only scanners for quantitative brain studies using three tracers with vastly different tracer distributions. Healthy volunteers underwent successive scans on HR+ and HRRT scanners (in random order) using either (R)-[(11)C]verapamil (n = 6), [(11)C]raclopride (n = 7) or [(11)C]flumazenil (n = 7). For all tracers, metabolite-corrected plasma-input functions were generated. After resolution matching, HRRT-derived kinetic parameter values correlated well with those of HR+ for all tracers (intraclass correlation coefficients ≥0.78), having a good absolute interscanner test-retest variability (≤15 %). However, systematic differences can be seen for HRRT-derived kinetic parameter values (range -13 to +15 %). Quantification of kinetic parameters based on plasma-input models leads to comparable results when spatial resolution between HRRT and HR+ data is matched. When using reference-tissue models, differences remain that are likely caused by differences in attenuation and scatter corrections and/or image reconstruction.
Neurology, Jan 7, 2014
To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the ... more To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[(11)C]verapamil (VPM)-PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function. Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- and postsurgery. Patients were followed up for a median of 6 years (range 4-7) after surgery. Pgp immunoreactivity in surgically resected hippocampal specimens was determined with immunohistochemistry. Optimal surgical outcome, defined as seizure freedom and withdrawal of antiepileptic drugs, was associated with higher temporal lobe Pgp function before surgery, higher Pgp-positive staining in surgically resected hippocampal specimens, and reduction in global Pgp function postoperatively, compared with nonoptimal surgery outcome. The data...
IEEE Nuclear Science Symposuim & Medical Imaging Conference, 2010
Page 1. Comparison of Methods for Quantification of rCBF on the HRRT PET Scanner Using [ 15 O]H2O... more Page 1. Comparison of Methods for Quantification of rCBF on the HRRT PET Scanner Using [ 15 O]H2O Matthew D. Walker, Member, IEEE, Maria Feldmann, Jose M. Anton-Rodriguez, Member, IEEE, Shaonan Wang, Julian ...
Schizophrenia Research, 2008
Physics in Medicine and Biology, 2002
Physiological quantification of dynamic PET data requires the determination of an input function,... more Physiological quantification of dynamic PET data requires the determination of an input function, preferably from plasma. A compartmental model relating a parent radiotracer, its radiolabelled metabolites and their exchange between plasma and erythrocytes is presented. This model allows for the time course of radioactivity measured in whole blood to be transformed into the time course of the radiotracer in plasma. The utility of this approach is illustrated with blood data collected on 30 human subjects injected with 6-[18F]fluoro-L-meta-tyrosine (FmT), a pre-synaptic dopaminergic radiotracer. A three-compartment four-parameter model is shown to yield significantly better fits to the blood data than related lower and higher order models. This model is found to be robust to measurement noise, and yet sensitive to metabolic changes induced by pretreatment with carbidopa. For FmT, the between-subject variations are shown to be small enough to warrant the use of a population-based correction; tissue time-activity curves were simulated to verify that this correction does not significantly affect the precision and accuracy of the derived rate constants. The unified blood model can be adapted for radiotracers other than FmT as long as the blood partition ratio of the parent radiotracer differs from that of its metabolites and/or the rate at which they equilibrate between plasma and erythrocytes is different.
Physics in Medicine and Biology, 2004
A non-invasive alternative to arterial blood sampling for the generation of a blood input functio... more A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[18F]fluoro-L-DOPA and one subject injected with [11C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 +/- 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest.