Novel 3D heart left ventricle muscle segmentation method for PET-gated protocol and its verification.

OBJECTIVE: The aim of this study was to propose and verify a universal method of left ventricular myocardium segmentation, able to operate on heart gated PET data with different sizes, shapes and uptake distributions. The proposed method can be classified as active model method and is based on the BEAS (B-spline Explicit Active Surface) algorithm published by Barbosa et al. The method was implemented within the Pmod PCARD software package. Method verification by comparison with reference software and phantom data is also presented in the paper. METHODS: The proposed method extends the BEAS model by defining mechanical features of the model: tensile strength and bending resistance. Formulas describing model internal energy increase during its stretching and bending are proposed. The segmentation model was applied to the data of 60 patients, who had undergone cardiac gated PET scanning. QGS by Cedars-Sinai and ECTb by Emory University Medical Centre served as reference software for comparing ventricular volumes. The method was also verified using data of left ventricular phantoms of known volume. RESULTS: The results of the proposed method are well correlated with the results of QGS (slope: 0.841, intercept: 0.944 ml, R2: 0.867) and ECTb (slope: 0.830, intercept: 2.109 ml, R2: 0.845). The volumes calculated by the proposed method were very close to the true cavity volumes of two different phantoms. CONCLUSIONS: The analysis of gated PET data by the proposed method results in volume measurements comparable to established methods. Phantom experiments demonstrate that the volume values correspond to the physical ones.

Comparison of Standardized Uptake Value Ratio Calculations in Amyloid Positron Emission Tomography Brain Imaging.

Amyloid positron emission tomography (PET) imaging with florbetapir 18F (18F-AV-45) allows in vivo assessment of cerebral amyloid load and can be used in the evaluation of progression of Alzheimer's disease (AD) and other dementias associated with b-amyloid. However, cortical amyloid deposition can occur in healthy cases, as well as in patients with AD and quantification of cortical amyloid burden can improve the 18F-AV-45 PET imaging evaluations. The quantification is mostly performed by cortical-to-cerebellum standardized uptake value ratio (SUVr). The aim of our study was to compare two methods for SUVr calculations in amyloid florbetapir 18F PET brain imaging. In amyloid florbetapir 18F PET brain imaging study, we imaged 42 cases with the mean age of 72.6 ± 9.9 (mean ± standard deviation). They were imaged on different PET/computed tomography systems with 369.0 ± 34.2 kBq of 18F florbetapir. Data were reconstructed using the vendor's reconstruction software. Corresponding magnetic resonance imaging (MRI) data were retrieved, and matched PET and MRI data were transferred to a common platform. Two methods were used for the calculation of the ratio of cortical-to-cerebellar signal (SUVr). One method was based on the MIM Software Inc., Version 6.4 software and only uses PET data. The second approach used the PMOD Neuro tool (version 3.5). This approach utilizes PET and corresponding MRI data (preferably T1-weighted) for better brain segmentation. For all the 42 cases, the average SUVr values for MIM and PMOD applications were 1.24 ± 0.26 and 1.22 ± 0.25, respectively, with a mean difference of 0.02 ± 0.15. The repeatability coefficient was 0.15 (12.3% of the mean). The Spearman's rank correlation coefficient was very high, r = 0.96. For amyloid-negative cases, the average SUVr values were lower than all group SUVr average values, 0.96 ± 0.07 and 1.00 ± 0.09, for MIM and PMOD applications, respectively. A mean difference was 0.04 ± 0.12, the repeatability coefficient was 0.12 (12.9% of the mean) and the Spearman's rank correlation coefficient was modest, r = 0.55. For amyloid-positive patients, the average SUVr values were higher than the same all group values, 1.34 ± 0.16 and 1.35 ± 0.20, respectively, with a mean difference of 0.01 ± 0.16. The repeatability coefficient was 0.16 (11.9% of the mean). The Spearman's rank correlation coefficient was high, r = 0.93. Our results indicated that the SUVr values derived using MIM and PMOD Neuro are effectively interchangeable and well correlated. However, PET template-based quantification (MIM approach) is clinically friendlier and easier to use. MRI template-based quantification (PMOD Neuro) better delineates different regions of the brain, can be used with any tracer, and therefore is more suitable for research.

Validation of pixel-wise parametric mapping of myocardial blood flow with ¹³NH3 PET in patients with hypertrophic cardiomyopathy.

PURPOSE: Transmural abnormalities in myocardial blood flow (MBF) are important causes of ischaemia in patients with left ventricular (LV) hypertrophy. The study aimed to test whether pixel-wise parametric mapping of (13)NH3 MBF can reveal transmural abnormalities in patients with hypertrophic cardiomyopathy (HCM). METHODS: We submitted 11 HCM patients and 9 age-matched controls with physiological LV hypertrophy to rest and stress (dipyridamole) (13)NH3 PET. We measured MBF using a compartmental model, and obtained rest and stress parametric maps. Pixel MBF values were reorganized to obtain subendocardial and subepicardial MBF of LV segments. RESULTS: MBF at rest was higher in the subendocardial than in the subepicardial layer: 0.78 ± 0.19 vs. 0.60 ± 0.18 mL/min/g in HCM patients; 0.92 ± 0.24 vs. 0.75 ± 0.24 mL/min/g in controls (both p < 0.0001). Transmural perfusion gradient (TPG = subendocardial MBF/subepicardial MBF) at rest was similar: 1.35 ± 0.31 in HCM patients; 1.28 ± 0.27 in controls (NS). During stress, controls maintained higher subendocardial MBF: 2.44 ± 0.54 vs. 1.96 ± 0.67 mL/min/g tissue (p < 0.0001), with a TPG of 1.33 ± 0.35 (NS vs. rest). In HCM patients, the difference between subendocardial and subepicardial MBF was reduced (1.46 ± 0.48 vs. 1.36 ± 0.48 mL/min/g tissue, p < 0.01) and TPG decreased to 1.11 ± 0.34 (p < 0.0001 vs. rest and vs. controls). In HCM patients 8 of 176 segments had subendocardial MBF less than -2 × SD of the mean, versus none of 144 segments in controls (p < 0.01). CONCLUSION: Pixel-wise parametric mapping of (13)NH3 MBF enables the identification of transmural abnormalities in patients with HCM.

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner.

Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers. EPiB decreased with age in PiB-positive subjects in bilateral superior parietal gyrus, bilateral temporoparietal region, right IFG, right PCC, and left parahippocampal gyrus but not in PiB-negative subjects. MCI had lower ePiB than HCS (left PCC, left IFG, and left and right hipp). Lowest ePiB values were found in MCI of 70 years and older, who also displayed high cortical PiB binding. This suggests that lowered regional cerebral blood flow indicated by ePiB is associated with age in the presence but not in the absence of amyloid pathology.

Metabotropic glutamate receptor 5 binding in patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.

Comparison of PET template-based and MRI-based image processing in the quantitative analysis of C11-raclopride PET.

BACKGROUND: Quantitative measures of 11C-raclopride receptor binding can be used as a correlate of postsynaptic D2 receptor density in the striatum, allowing 11C-raclopride positron emission tomography (PET) to be used for the differentiation of Parkinson's disease from atypical parkinsonian syndromes. Comparison with reference values is recommended to establish a reliable diagnosis. A PET template specific to raclopride may facilitate direct computation of parametric maps without the need for an additional MR scan, aiding automated image analysis. METHODS: Sixteen healthy volunteers underwent a dynamic 11C-raclopride PET and a high-resolution T1-weighted MR scan of the brain. PET data from eight healthy subjects was processed to generate a raclopride-specific PET template normalized to standard space. Subsequently, the data processing based on the PET template was validated against the standard magnetic resonance imaging (MRI)-based method in 8 healthy subjects and 20 patients with suspected parkinsonian syndrome. Semi-quantitative image analysis was performed in Montreal Neurological Institute (MNI) and in original image space (OIS) using VOIs derived from a probabilistic brain atlas previously validated by Hammers et al. (Hum Brain Mapp, 15:165-174, 2002). RESULTS: The striatal-to-cerebellar ratio (SCR) of 11C-raclopride uptake obtained using the PET template was in good agreement with the MRI-based image processing method, yielding a Lin's concordance coefficient of 0.87. Bland-Altman analysis showed that all measurements were within the ±1.96 standard deviation range. In all 20 patients, the PET template-based processing was successful and manual volume of interest optimization had no further impact on the diagnosis of PD in this patient group. A maximal difference of <5% was found between the measured SCR in MNI space and OIS. CONCLUSIONS: The PET template-based method for automated quantification of postsynaptic D2 receptor density is simple to implement and facilitates rapid, robust and reliable image analysis. There was no significant difference between the SCR values obtained with either PET- or MRI-based image processing. The method presented alleviates the clinical workflow and facilitates automated image analysis.

Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography.

Nicotine addiction is a major public health problem, resulting in primary glutamatergic dysfunction. We measured the glutamate receptor binding in the human brain and provided direct evidence for the abnormal glutamate system in smokers. Because antagonism of the metabotropic glutamate receptor 5 (mGluR5) reduced nicotine self-administration in rats and mice, mGluR5 is suggested to be involved in nicotine addiction. mGluR5 receptor binding specifically to an allosteric site was observed by using positron emission tomography with [(11)C]ABP688. We found a marked global reduction (20.6%; P < 0.0001) in the mGluR5 distribution volume ratio (DVR) in the gray matter of 14 smokers. The most prominent reductions were found in the bilateral medial orbitofrontal cortex. Compared with 14 nonsmokers, 14 ex-smokers had global reductions in the average gray matter mGluR5 DVR (11.5%; P < 0.005), and there was a significant difference in average gray matter mGluR5 DVR between smokers and ex-smokers (9.2%; P < 0.01). Clinical variables reflecting current nicotine consumption, dependence and abstinence were not correlated with mGluR5 DVR. This decrease in mGluR5 receptor binding may be an adaptation to chronic increases in glutamate induced by chronic nicotine administration, and the decreased down-regulation seen in the ex-smokers could be due to incomplete recovery of the receptors, especially because the ex-smokers were abstinent for only 25 wk on average. These results encourage the development and testing of drugs against addiction that directly target the glutamatergic system.

PET/MR imaging of bone lesions--implications for PET quantification from imperfect attenuation correction.

PURPOSE: Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging. METHODS: In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference. RESULTS: Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4% (range 1.5-30.8%) and 3.2 ± 1.7% (range 0.2-4%), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4% (range 9.9-23.5%) and for osteolytic spine lesions, 7.2 ± 1.7% (range 4.9-9.3%), respectively. CONCLUSION: CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake values in PET/MR imaging.

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water.

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

Repeatability of FDG quantification in tumor imaging: averaged SUVs are superior to SUVmax.

PURPOSE: Reliable 18F-fluorodeoxyglucose (FDG) uptake quantification is crucial for cancer treatment monitoring. While interobserver variability has been found to be lower for a maximum standard uptake value (SUV)max than for an averaged SUV (SUVmean), the repeatability has not been investigated yet. In this study, we determined the repeatability of SUV values in two sequential measurements 5 min apart. METHODS: Positron emission tomography data of malignant chest tumors were acquired dynamically during 45 min in 20 patients. SUV values were derived from the hottest (SUVmax), the mean of the 5 (SUV5) and 10 (SUV10) hottest voxels and the mean of a volume of interest (SUVmean). The repeatability of the SUV measurements was determined as the standard deviation of the difference between the values at 40 and 45 min and represented as Bland-Altman graphs. RESULTS: The standard deviation of the difference between the two sequential scans for SUVmax, SUV5, SUV10 and SUVmean was 1.01, 0.53, 0.37 and 0.28. CONCLUSION: The repeatability of SUV is markedly increased by deriving the value from multiple voxels. Compared to SUVmax, the variability in SUV measurements is reduced by a factor of 2.7 (2.7=1.01/0.37) if 10 voxels are pooled.

Assessment of serotonin release capacity in the human brain using dexfenfluramine challenge and [18F]altanserin positron emission tomography.

Although alterations of serotonin (5-HT) system functioning have been proposed for a variety of psychiatric disorders, a direct method quantitatively assessing 5-HT release capacity in the living human brain is still lacking. Therefore, we evaluated a novel method to assess 5-HT release capacity in vivo using dexfenfluramine challenge and [(18)F]altanserin positron emission tomography (PET). Thirteen healthy male subjects received placebo and single oral doses of 40 mg (n = 6) or 60 mg (n = 7) of the potent 5-HT releaser dexfenfluramine separated by an interval of 14 days. Three further subjects received placebo on both days. Two hours after placebo/drug administration, 250 MBq of the 5-HT(2A) receptor selective PET-radiotracer [(18)F]altanserin was administered intravenously as a 30s bolus. Dynamic PET data were subsequently acquired over 90 min. Moreover, arterial blood samples were drawn for measurement of total activity and metabolite correction of the input function. Dexfenfluramine as well as cortisol and prolactin plasma concentration-time profiles was quantitatively determined. Tracer distribution volumes for five volumes-of-interest (prefrontal and occipital cortex, insula, thalamus, caudatum) were calculated by the Logan plot and a 2-tissue compartment model. Dexfenfluramine dose-dependently decreased the total distribution volume of [(18)F]altanserin in cortical regions independent of the PET modeling approach. Cortisol and prolactin plasma concentrations were dose-dependently increased by dexfenfluramine. The decrease in cortical [(18)F]altanserin receptor binding under dexfenfluramine was correlated with the increase of plasma prolactin. These data suggest that the combination of a dexfenfluramine-induced 5-HT release and subsequent assessment of 5-HT(2A) receptor availability with [(18)F]altanserin PET is suitable to measure cortical 5-HT release capacity in the human brain.

Simplified quantification of FDG metabolism in tumors using the autoradiographic method is less dependent on the acquisition time than SUV.

UNLABELLED: The standard uptake value (SUV) is the most often used semi-quantitative measure of (18)F-fluorodeoxyglucose (FDG) uptake. We tested the hypothesis that the autoradiographic method with a population-based input curve yields an approximation of FDG metabolism represented by the flux value Ki, which is less dependent on the acquisition time point than SUV. METHODS: We analyzed 20 patients with chest tumors (16 males, age 65±10 years). After injection of 350 MBq FDG using the INTEGO PET infusion system, a series of 35 scans of 10- to 300-s duration were acquired until 45 min. FDG flux was calculated using the Patlak method (Ki(patlak)) and also quantified with the autoradiographic method using the last acquisition only and the individual image-derived input function (Ki(autoreal)), as well as with a population-based input function (Ki(autonorm)). In a simulation study, the time courses of tumor SUV, tumor-to-blood ratio and tumor Ki values were calculated from 30 to 90 min. RESULTS: The FDG flux values (Ki) of the different tumors, obtained with the autoradiographic methods and the Patlak method, showed a high correlation. The simulation study showed a 16.8±3.3% increase in the SUV values from 50 to 70 min, but only a 1.3±2.8% change in the Ki values calculated with the autoradiographic method. CONCLUSION: Compared to the SUV, the autoradiographic Ki values are advantageous for various reasons. First, they are much less dependent on the time of acquisition than the SUV. Second, their calculation does not require the knowledge of the body weight or the injected activity. Furthermore, the values are comparable to the ones obtained with the widely accepted Patlak method. The method can be easily implemented in a clinical setting, as it uses only one static scan.

Semiconductor detectors allow low-dose-low-dose 1-day SPECT myocardial perfusion imaging.

UNLABELLED: Cadmium zinc telluride (CZT) detectors with linear counting rate response enable count subtraction in sequential scanning. We evaluated whether count subtraction eliminated the need for higher activity doses in the second part of the 1-d stress-rest myocardial perfusion imaging (MPI) protocol. METHODS: For 50 patients (mean age ± SD, 66 ± 12 y) with visually abnormal (n = 42) or equivocal (n = 8) adenosine-stress MPI (320 MBq of (99m)Tc-tetrofosmin) on a CZT camera, rest MPI was performed with a low dose (320 MBq) and repeated after injection of an additional 640 MBq of (99m)Tc-tetrofosmin to achieve a standard 3-fold increased dose at rest (960 MBq), compared with stress (320 MBq). Low-dose rest myocardial perfusion images were reconstructed after subtracting the background activity of the preceding stress scan. Segmental percentage tracer uptake of the 2 rest myocardial perfusion images (320 vs. 960 MBq) was compared using intraclass correlation and Bland-Altman limits of agreement. Patient- and coronary territory-based clinical agreement was assessed. RESULTS: The standard protocol revealed ischemia in 34 (68%) and a fixed defect in 8 (16%) patients, of whom 33 (97%) and 8 (100%) were correctly identified by low-dose MPI (clinical agreement, 98%). Segmental uptake correlated well between low- and standard-dose rest scans (r = 0.94, P < 0.001; Bland-Altman limits of agreement, -11 to +11%). Defect extent was 14.4% (low-dose) versus 13.1% (standard-dose) at rest (P = not statistically significant) and 26.6% at stress (P < 0.001 vs. rest scans). CONCLUSION: These promising results suggest that accurate assessment of ischemic myocardial disease is feasible with a low-dose-low-dose 1-d SPECT MPI protocol using a CZT device.

Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C]ABP688 PET and postmortem study.

OBJECTIVE: Clinical and preclinical evidence suggests a hyperactive glutamatergic system in clinical depression. Recently, the metabotropic glutamate receptor 5 (mGluR5) has been proposed as an attractive target for novel therapeutic approaches to depression. The goal of this study was to compare mGluR5 binding (in a positron emission tomography [PET] study) and mGluR5 protein expression (in a postmortem study) between individuals with major depressive disorder and psychiatrically healthy comparison subjects. METHOD: Images of mGluR5 receptor binding were acquired using PET with [(11)C]ABP688, which binds to an allosteric site with high specificity, in 11 unmedicated individuals with major depression and 11 matched healthy comparison subjects. The amount of mGluR5 protein was investigated using Western blot in postmortem brain samples of 15 depressed individuals and 15 matched comparison subjects. RESULTS: The PET study revealed lower levels of regional mGluR5 binding in the prefrontal cortex, the cingulate cortex, the insula, the thalamus, and the hippocampus in the depression group relative to the comparison group. Severity of depression was negatively correlated with mGluR5 binding in the hippocampus. The postmortem study showed lower levels of mGluR5 protein expression in the prefrontal cortex (Brodmann's area 10) in the depression group relative to the comparison group, while prefrontal mGluR1 protein expression did not differ between groups. CONCLUSIONS: The lower levels of mGluR5 binding observed in the depression group are consonant with the lower levels of protein expression in brain tissue in the postmortem depression group. Thus, both studies suggest that basal or compensatory changes in excitatory neurotransmission play roles in the pathophysiology of major depression.

Evaluation of a bolus/infusion protocol for 11C-ABP688, a PET tracer for mGluR5.

UNLABELLED: (11)C-ABP-688 is a selective tracer for the mGluR5 receptor. Its kinetics is fast and thus favourable for an equilibrium approach to determine receptor-related parameters. The purpose of this study was to test the hypothesis that the pattern of the (11)C-ABP688 uptake using a bolus-plus-infusion (B/I) protocol at early time points corresponds to the perfusion and at a later time point to the total distribution volume. METHODS: A bolus and a B/I study (1 h each) was performed in five healthy male volunteers. With the B/I protocol, early and late scans were normalized to gray matter, cerebellum and white matter. The same normalization was done on the maps of the total distribution volume (Vt) and K(1) which were calculated in the study with bolus only injection and the Logan method (Vt) and a two-tissue compartment model (K(1)). RESULTS: There was an excellent correlation close to the identity line between the pattern of the late uptake in the B/I study and Vt of the bolus-only study for all three normalizations. The pattern of the early uptake in the B/I study correlated well with the K(1) maps, but only when normalized to gray matter and cerebellum, not to white matter. CONCLUSION: It is demonstrated that with a B/I protocol the (11)C-ABP688 distribution in late scans reflects the pattern of the total distribution volume and is therefore a measure for the density pattern of mGluR5. The early scans following injection are related to blood flow, although not in a fully quantitative manner. The advantage of the B/I protocol is that no arterial blood sampling is required, which is advantageous in clinical studies.

Integrating imaging modalities: what makes sense from a workflow perspective?

PURPOSE: From a workflow/cost perspective integrated imaging is not an obvious solution. An analysis of scanning costs as a function of system cost and relevant imaging times is presented. This analysis ignores potential clinical advantages of integrated imaging. METHODS: An analysis comparing separate vs integrated imaging costs was performed by deriving pertinent equations and using reasonable cost numbers for imaging devices and systems, room and other variable costs. Integrated systems were divided into those sequentially and simultaneously. Sequential scanning can be done with two devices placed in a single or in two different scanning rooms. Graphs were derived which represent the cost difference between integrated imaging system options and their separate counterparts vs scanning time on one of the devices and cost ratio of an integrated system and its counterpart of separate devices. RESULTS: Integrated systems are favoured by the fact that patients have to be up- and downloaded only once. If imaging times become longer than patient changing times, imaging on separate devices is advantageous. An integrated imaging cost advantage is achieved if the integrated systems typically and overall cost three fourths or less of the separate systems. If PET imaging takes 15 min or less, PET/CT imaging costs less than separate PET and CT imaging, while this time is below 5 min for SPECT/CT. A two-room integrated system has the added advantage that patient download time is not cost relevant, when imaging times on the two devices differ by more than the patient download time. CONCLUSION: PET/CT scanning is a cost-effective implementation of an integrated system unlike most current SPECT/CT systems. Integration of two devices in two rooms by a shuttle seems the way how to make PET/MR cost-effective and may well also be a design option for SPECT/CT systems.

A beta-scintillator for surface measurements of radiotracer kinetics in the intact rodent cortex.

Beta+-sensitive probes are useful tools for the measurement of radiotracer kinetics in small animals. They allow the cost-effective development of new PET tracers and offer the possibility to investigate a variety of cerebral processes. The study's main aim was the in vivo evaluation of a probe system for cerebral surface acquisitions. The detector system is a 0.2-mm thick scintillating disk of 3-mm diameter, positioned close to the cerebral surface. The study consists of 4 subparts: (1) simulation of the detection volume, (2) direct comparison with the classic intracortical beta probe regarding its capability to acquire kinetic data, (3) test of the ability to detect local tracer accumulations during infraorbital nerve (ION) electrostimulation and (4) demonstration of the feasibility to measure tracer kinetics in awake animals. Kinetic data acquired with 18F-fluorodeoxyglucose and 15O-H2O were fitted with standard compartment models. The surface probe measurements were in good agreement with those obtained using the intracortical scintillator. ION electrostimulation induced a marked increase in tracer accumulation adequately detected by the surface probe. In the head-fixed animal, a marked change in FDG kinetics was detected between the awake and anesthetized state. The novel surface probe system proved to be a valuable instrument for in vivo radiotracer studies of the cerebral cortex. Its main advantage is the absence of any tissue damage. In addition, serial acquisitions of tracer kinetics in the awake animal turned out to be feasible.

Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

UNLABELLED: The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). METHODS: 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). RESULTS: Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps < 0.0001). The mean +/- SD differences in global MBF measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P < 0.001). CONCLUSION: For this scanner type, quantitative measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.

Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: validation of a new fast factor analysis.

BACKGROUND: Factor analysis (FA) is an established method for separating myocardium from blood pool by use of oxygen 15-labeled water and positron emission tomography for analyzing myocardial blood flow (MBF). Conventional FA methods generating images from sinograms (sinoFA) are time-consuming, whereas FA can be performed on the reconstructed images (reconFA) in a fraction of time. We validated the MBF values obtained by reconFA versus sinoFA. METHODS AND RESULTS: In 23 volunteers (mean age, 26.6 +/- 3.4 years) MBF was calculated from sinoFA and reconFA and blindly reanalyzed 1 month later by the same observer. Intraobserver agreement and reconFA-versus-sinoFA agreement were assessed according to Bland and Altman (BA). Reproducibility proved excellent for global sinoFA (r = 0.968; P < .001; BA limits, -0.617 to 0.676 mL x min(-1) x g(-1)) and slightly superior for reconFA (r = 0.979; P < .001; BA limits, -0.538 to 0.558 mL x min(-1) x g(-1)), with wider limits of agreement for segmental MBF from sinoFA (r = 0.777; P < .001; BA limits, -1.676 to 1.656 mL x min(-1) x g(-1)) and reconFA (r = 0.844; P < .001; BA limits, -1.999 to 1.992 mL x min(-1) x g(-1)). In addition, sinoFA and reconFA showed excellent correlation (r = 0.975, P < .001) and agreement (BA limits, -0.528 to 0.648 mL x min(-1) x g(-1)) for global and segmental values (r = 0.955; P < .001; BA limits, -1.371 to 1.491 mL x min(-1) x g(-1)). CONCLUSIONS: Use of reconFA allows rapid and reliable quantitative MBF assessment with O-15-labeled water.

[18FDG] PET-CT-based intensity-modulated radiotherapy treatment planning of head and neck cancer.

PURPOSE: To define the best threshold for tumor volume delineation of the (18) fluoro-2-deoxy-glucose positron emission tomography ((18)FDG-PET) signal for radiotherapy treatment planning of intensity-modulated radiotherapy (IMRT) in head and neck cancer. METHODS AND MATERIALS: In 25 patients with head-and-neck cancer, CT-based gross tumor volume (GTV(CT)) was delineated. After PET-CT image fusion, window level (L) was adapted to best fit the GTV(CT), and GTV(PET) was delineated. Tumor maximum (S) and background uptake (B) were measured, and the threshold of the background-subtracted tumor maximum uptake (THR) was used for PET signal segmentation. Gross tumor volumes were expanded to planning target volumes (PTVs) and analyzed. RESULTS: The mean value of S was 40 kBq/mL, S/B ratio was 16, and THR was 26%. The THR correlated with S (r = -0.752), but no correlation between THR and the S/B ratio was seen (r = -0.382). In 77% of cases, S was >30 kBq/mL, and in 23% it was 30% +/- 1.6% kBq/mL and 40% in tumors with S