Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
Overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresista... more Overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, (11)C-Phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of (11)C-Phenytoin studies in humans. Dynamic (11)C-Phenytoin PET scans of six healthy volunteers with arterial sampling were acquired twice on the same day, and analysed using single and two tissue compartment models with and without a blood volume parameter. Global and regional test-retest (TRT) variability was determined for both K1 and VT. According to the Akaike Information Criterion, the reversible single tissue compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5 to 16.9% for K1 and from 0.5% to 5.8% for VT, respectively. Larger volumes of interest showed better repeatabilities than smaller regions. A 45 minutes scan provided...
... Research Tomograph Hugo WAM de Jong, Ronald Boellaard, Mark Lenox, Christiaan Michel, and Adr... more ... Research Tomograph Hugo WAM de Jong, Ronald Boellaard, Mark Lenox, Christiaan Michel, and Adriaan A. Lammertsma ... The cylinders were filled with varying activity levels of F-18 (hot). In addition, a scan without activity (cold) was acquired. ...
The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomogr... more The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. Recently, a 3D filtered backprojection (3D-FBP) reconstruction method has been implemented to reduce bias in short duration frames, currently observed in 3D ordinary Poisson OSEM (3D-OP-OSEM) reconstructions. Further improvements might be expected using a new method of variance reduction on randoms (VRR) based on coincidence histograms instead of using the delayed window technique (DW) to estimate randoms. The goal of this study was to evaluate VRR in combination with 3D-OP-OSEM and 3D-FBP reconstruction techniques. To this end, several phantom studies and a human brain study were performed. For most phantom studies, 3D-OP-OSEM showed higher accuracy of observed activity concentrations with VRR than with DW. However, both positive and negative deviations in reconstructed activity concentrations and large biases of grey to white matter contrast ratio (up to 88%) were still observed as a function of scan statistics. Moreover 3D-OP-OSEM+VRR also showed bias up to 64% in clinical data, i.e. in some pharmacokinetic parameters as compared with those obtained with 3D-FBP+VRR. In the case of 3D-FBP, VRR showed similar results as DW for both phantom and clinical data, except that VRR showed a better standard deviation of 6-10%. Therefore, VRR should be used to correct for randoms in HRRT PET studies.
Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Re... more Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding. Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue. Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96). SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 4, 2014
This study compared several parametric imaging methods to determine the optimal approach for visu... more This study compared several parametric imaging methods to determine the optimal approach for visual assessment of parametric Pittsburgh compound-B ((11)C-PIB) PET images to detect cortical amyloid deposition in different memory clinic patient groups. Dynamic (11)C-PIB scanning of 120 memory clinic patients was performed. Parametric nondisplaceable binding potential (BPND) images were compared with standardized uptake value (SUV) and SUV ratio images. Images were visually assessed by 3 independent readers, and both interreader and intermethod agreement was determined. Both 90-min (Fleiss κ = 0.88) and 60-min (Fleiss κ = 0.89) BPND images showed excellent interreader agreement, whereas agreement was good to moderate for SUV ratio images (Fleiss κ = 0.68) and SUV images (Fleiss κ = 0.59). Intermethod agreement varied substantially between readers, although BPND images consistently showed the best performance. The use of BPND images provided the highest interreader and intermethod agree...
Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F... more Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
Overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresista... more Overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, (11)C-Phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of (11)C-Phenytoin studies in humans. Dynamic (11)C-Phenytoin PET scans of six healthy volunteers with arterial sampling were acquired twice on the same day, and analysed using single and two tissue compartment models with and without a blood volume parameter. Global and regional test-retest (TRT) variability was determined for both K1 and VT. According to the Akaike Information Criterion, the reversible single tissue compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5 to 16.9% for K1 and from 0.5% to 5.8% for VT, respectively. Larger volumes of interest showed better repeatabilities than smaller regions. A 45 minutes scan provided...
... Research Tomograph Hugo WAM de Jong, Ronald Boellaard, Mark Lenox, Christiaan Michel, and Adr... more ... Research Tomograph Hugo WAM de Jong, Ronald Boellaard, Mark Lenox, Christiaan Michel, and Adriaan A. Lammertsma ... The cylinders were filled with varying activity levels of F-18 (hot). In addition, a scan without activity (cold) was acquired. ...
The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomogr... more The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. Recently, a 3D filtered backprojection (3D-FBP) reconstruction method has been implemented to reduce bias in short duration frames, currently observed in 3D ordinary Poisson OSEM (3D-OP-OSEM) reconstructions. Further improvements might be expected using a new method of variance reduction on randoms (VRR) based on coincidence histograms instead of using the delayed window technique (DW) to estimate randoms. The goal of this study was to evaluate VRR in combination with 3D-OP-OSEM and 3D-FBP reconstruction techniques. To this end, several phantom studies and a human brain study were performed. For most phantom studies, 3D-OP-OSEM showed higher accuracy of observed activity concentrations with VRR than with DW. However, both positive and negative deviations in reconstructed activity concentrations and large biases of grey to white matter contrast ratio (up to 88%) were still observed as a function of scan statistics. Moreover 3D-OP-OSEM+VRR also showed bias up to 64% in clinical data, i.e. in some pharmacokinetic parameters as compared with those obtained with 3D-FBP+VRR. In the case of 3D-FBP, VRR showed similar results as DW for both phantom and clinical data, except that VRR showed a better standard deviation of 6-10%. Therefore, VRR should be used to correct for randoms in HRRT PET studies.
Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Re... more Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding. Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue. Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96). SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 4, 2014
This study compared several parametric imaging methods to determine the optimal approach for visu... more This study compared several parametric imaging methods to determine the optimal approach for visual assessment of parametric Pittsburgh compound-B ((11)C-PIB) PET images to detect cortical amyloid deposition in different memory clinic patient groups. Dynamic (11)C-PIB scanning of 120 memory clinic patients was performed. Parametric nondisplaceable binding potential (BPND) images were compared with standardized uptake value (SUV) and SUV ratio images. Images were visually assessed by 3 independent readers, and both interreader and intermethod agreement was determined. Both 90-min (Fleiss κ = 0.88) and 60-min (Fleiss κ = 0.89) BPND images showed excellent interreader agreement, whereas agreement was good to moderate for SUV ratio images (Fleiss κ = 0.68) and SUV images (Fleiss κ = 0.59). Intermethod agreement varied substantially between readers, although BPND images consistently showed the best performance. The use of BPND images provided the highest interreader and intermethod agree...
Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F... more Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses...
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