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Lobar cerebral microbleeds are a characteristic neuroimaging finding in cerebral amyloid angiopathy (CAA) but can also be found in hypertensive arteriolosclerosis. We aimed to investigate whether CAA is more associated with intracortical lobar microbleeds than hypertensive arteriosclerosis. Ninety-one survivors of spontaneous intracerebral hemorrhage with at least one lobar microbleed were included and underwent brain MRI and amyloid PET. We categorized lobar microbleeds as intracortical, juxtacortical, or subcortical. We assessed the associations between the lobar microbleed categories and microangiopathy subtypes or cerebral amyloid load based on the Pittsburgh Compound-B PET standardized uptake value ratio (SUVR). Patients with CAA had a higher prevalence of intracortical lobar microbleeds (80.0% vs. 50.8%, P = 0.011) and lower prevalence of subcortical lobar microbleeds (13.3% vs. 60.1%, P < 0.001) than patients with hypertensive arteriolosclerosis. Strictly intracortical/juxtacortical lobar microbleeds were associated with CAA (OR 18.9 [1.9–191.4], P = 0.013), while the presence of subcortical lobar microbleeds was associated with hypertensive arteriolosclerosis (OR 10.9 [1.8–68.1], P = 0.010). Amyloid retention was higher in patients with strictly intracortical/juxtacortical CMBs than those without (SUVR = 1.15 [1.05–1.52] vs. 1.08 [1.02–1.19], P = 0.039). Amyloid retention positively correlated with the number of intracortical lobar microbleeds (P < 0.001) and negatively correlated with the number of subcortical lobar microbleeds (P = 0.018). CAA and cortical amyloid deposition are more strongly associated with strictly intracortical/juxtacortical microbleeds than subcortical lobar microbleeds. Categorization of lobar microbleeds based on anatomical location may help differentiate the underlying microangiopathy and potentially improve the accuracy of current neuroimaging criteria for cerebral small vessel disease. [ABSTRACT FROM AUTHOR]

Purpose : Pittsburgh Compound-B (11C-PiB) and 18F-florbetapir are amyloid-β (Aβ) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aβ monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aβ radiotracers were used. To study the consequences of using different Aβ radiotracers to measure Aβ clearance, we performed a head-to-head comparison of 11C-PiB and 18F-florbetapir in a Phase 2/3 clinical trial of anti-Aβ monoclonal antibodies. Methods: Sixty-six mutation-positive participants enrolled in the gantenerumab and placebo arms of the first Dominantly Inherited Alzheimer Network Trials Unit clinical trial (DIAN-TU-001) underwent both 11C-PiB and 18F-florbetapir PET imaging at baseline and during at least one follow-up visit. For each PET scan, regional standardized uptake value ratios (SUVRs), regional Centiloids, a global cortical SUVR, and a global cortical Centiloid value were calculated. Longitudinal changes in SUVRs and Centiloids were estimated using linear mixed models. Differences in longitudinal change between PET radiotracers and between drug arms were estimated using paired and Welch two sample t-tests, respectively. Simulated clinical trials were conducted to evaluate the consequences of some research sites using 11C-PiB while other sites use 18F-florbetapir for Aβ PET imaging. Results: In the placebo arm, the absolute rate of longitudinal change measured by global cortical 11C-PiB SUVRs did not differ from that of global cortical 18F-florbetapir SUVRs. In the gantenerumab arm, global cortical 11C-PiB SUVRs decreased more rapidly than global cortical 18F-florbetapir SUVRs. Drug effects were statistically significant across both Aβ radiotracers. In contrast, the rates of longitudinal change measured in global cortical Centiloids did not differ between Aβ radiotracers in either the placebo or gantenerumab arms, and drug effects remained statistically significant. Regional analyses largely recapitulated these global cortical analyses. Across simulated clinical trials, type I error was higher in trials where both Aβ radiotracers were used versus trials where only one Aβ radiotracer was used. Power was lower in trials where 18F-florbetapir was primarily used versus trials where 11C-PiB was primarily used. Conclusion: Gantenerumab treatment induces longitudinal changes in Aβ PET, and the absolute rates of these longitudinal changes differ significantly between Aβ radiotracers. These differences were not seen in the placebo arm, suggesting that Aβ-clearing treatments may pose unique challenges when attempting to compare longitudinal results across different Aβ radiotracers. Our results suggest converting Aβ PET SUVR measurements to Centiloids (both globally and regionally) can harmonize these differences without losing sensitivity to drug effects. Nonetheless, until consensus is achieved on how to harmonize drug effects across radiotracers, and since using multiple radiotracers in the same trial may increase type I error, multisite studies should consider potential variability due to different radiotracers when interpreting Aβ PET biomarker data and, if feasible, use a single radiotracer for the best results. Trial registration: ClinicalTrials.gov NCT01760005. Registered 31 December 2012. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Specificity and sensitivity of positron emission tomography (PET) radiopharmaceuticals targeting fibrillar amyloid-β (Aβ) deposits is high for detection of neuritic Aβ plaques, a mature form of Aβ deposits which often have dense Aβ core (i.e., cored plaques). However, imaging-to-autopsy validation studies of amyloid PET radioligands have identified several false positive cases all of which had mainly diffuse Aβ plaques (i.e., plaques without neuritic pathology or dense amyloid core), and high amyloid PET signal was reported in the striatum where diffuse plaques predominate in Alzheimer's disease (AD). Relative contributions of different plaque types to amyloid PET signal is unclear, particularly in neocortical areas where they are intermixed in AD. In vitro binding assay and autoradiography were performed using [3H]flutemetamol and [3H]Pittsburgh Compound-B (PiB) in frozen brain homogenates from 30 autopsy cases including sporadic AD and non-AD controls with a range of brain Aβ burden and plaque density. Fixed tissue sections of frontal cortex and caudate from 10 of the AD cases were processed for microscopy using fluorescent derivatives of flutemetamol (cyano-flutemetamol) and PiB (cyano-PiB) and compared to Aβ immunohistochemistry and pan-amyloid (X-34) histology. Using epifluorescence microscopy, percent area coverage and fluorescence output values of cyano-PiB- and cyano-flutemetamol-labeled plaques in two-dimensional microscopic fields were then calculated and combined to obtain integrated density measurements. Using confocal microscopy, we analysed total fluorescence output of the entire three-dimensional volume of individual cored plaques and diffuse plaques labeled with cyano-flutemetamol or cyano-PiB. [3H]Flutemetamol and [3H]PiB binding values in tissue homogenates correlated strongly and their binding pattern in tissue sections, as seen on autoradiograms, overlapped the pattern of Aβ-immunoreactive plaques on directly adjacent sections. Cyano-flutemetamol and cyano-PiB fluorescence was prominent in cored plaques and less so in diffuse plaques. Across brain regions and cases, percent area coverage of cyano-flutemetamol-labeled plaques correlated strongly with cyano-PiB-labeled and Aβ-immunoreactive plaques. For both ligands, plaque burden, calculated as percent area coverage of all Aβ plaque types, was similar in frontal cortex and caudate regions, while integrated density values were significantly greater in frontal cortex, which contained both cored plaques and diffuse plaques, compared to the caudate, which contained only diffuse plaques. Three-dimensional analysis of individual plaques labeled with either ligand showed that total fluorescence output of a single cored plaque was equivalent to total fluorescence output of approximately three diffuse plaques of similar volume. Our results indicate that [18F]flutemetamol and [11C]PiB PET signal is influenced by both diffuse plaques and cored plaques, and therefore is likely a function of plaque size and density of Aβ fibrils in plaques. Brain areas with large volumes/frequencies of diffuse plaques could yield [18F]flutemetamol and [11C]PiB PET retention levels comparable to brain regions with a lower volume/frequency of cored plaques. [ABSTRACT FROM AUTHOR]

Background: This study was to investigate the significance of 11C-Pittsburgh B (PIB) PET/CT in patients with suspected cardiac amyloidosis compared with 99mTc-aprotinin scintigraphy.Methods: Thirteen consecutive patients with suspected cardiac amyloidosis were considered for enrolment in this prospective pilot study. Participants were scheduled to undergo a series of 11C-PIB PET/CT and 99mTc-aprotinin within a 2-month period. Finally, we evaluated nine cases who underwent both imaging modalities, and compared imaging results with clinical and pathological results and prognosis.Results: Six of the 9 patients who underwent both imaging modalities were diagnosed with amyloidosis, of whom 3 patients were diagnosed with cardiac amyloidosis from endomyocardial biopsy. These 3 patients with positive 11C-PIB uptake at the left ventricle wall showed worsening of cardiac function progressing in the short term or death caused by acute exacerbation of chronic heart failure. Six of 8 patients with positive uptake on 99mTc-aprotinin presented with amyloid deposition in the left ventricle wall, but symptoms remained stable if results of 11C-PIB were not positive.Conclusion: In a small sample of subjects, the present study showed that 11C-PIB accumulation in myocardium indicated cardiac amyloidosis with poor prognosis. Uptake of 11C-PIB may be related to progressive amyloid deposition to the heart and can predict patient prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Amyloid (Aβ) brain deposition can occur in cognitively normal individuals and is associated with cortical volume abnormalities. Aβ-related volume changes are inconsistent across studies. Since volume is composed of surface area and thickness, the relative contribution of Aβ deposition on each of these metrics remains to be understood in cognitively normal individuals. Methods: A group of 104 cognitively normal individuals underwent neuropsychological assessment, PiB-PET scan, and MRI acquisition. Surface-based cortical analyses were performed to investigate the effects of cortical and subcortical Aβ burden on cortical volume, thickness, and surface area. Mediation analyses were used to study the effect of thickness and surface area on Aβ-associated volume changes. We also investigated the relationships between structural metrics in clusters with abnormal morphology and regions underlying resting-state functional networks and cognitive performance. Results: Cortical Aβ was not associated with cortical morphology. Subcortical Aβ burden was associated with changes in cortical volume, thickness, and surface area. Aβ-associated volume changes were driven by cortical surface area with or without thickness but never by thickness alone. Aβ-associated changes overlapped greatly with regions from the default mode network and were associated with lower performance in visuospatial abilities, episodic memory, and working memory. Conclusions: In cognitively normal individuals, subcortical Aβ is associated with cortical volume, and this effect was driven by surface area with or without thickness. Aβ-associated cortical changes were found in the default mode network and affected cognitive performance. Our findings demonstrate the importance of studying subcortical Aβ and cortical surface area in normal ageing. [ABSTRACT FROM AUTHOR]

Background: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing 11C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.Methods: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.Results: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min-1, P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.Conclusion: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis. [ABSTRACT FROM AUTHOR]

Purpose: One of the interesting features of the amyloid tracer Pittsburgh compound B (PiB) is that it generates a signal in the white matter (WM) in both healthy subjects and cognitively impaired individuals. This characteristic gave rise to the possibility that PiB could be used to trace WM pathology. In a group of cognitively healthy elderly we examined PiB retention in normal-appearing WM (NAWM) and WM lesions (WML), one of the most common brain pathologies in aging. Methods: We segmented WML and NAWM on fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9 ± 10.0, 71 % women). PiB PET images were corrected for partial volume effects and coregistered to FLAIR images and WM masks. WML and NAWM PiB signals were then extracted. Results: PiB retention in WML was lower than in NAWM ( p < 0.001, 14.6 % reduction). This was true both for periventricular WML ( p < 0.001, 17.8 % reduction) and deep WML ( p = 0.001, 7.5 % reduction). Conclusion: PiB binding in WM is influenced by the presence of WML, which lower the signal. Our findings add to the growing evidence that PiB can depict WM pathology and should prompt further investigations into PiB binding targets in WM. [ABSTRACT FROM AUTHOR]

Cognitive impairment and dementia are significant sequelae of Parkinson disease (PD) and comprise a key feature of dementia with Lewy bodies (DLB), a disease with similar clinical and neuropathological features. Multiple independent causes have been implicated in PD dementia (PDD) and DLB, among them the accumulation of β-amyloid, a neuropathological hallmark of Alzheimer disease. Over the last decade, PET imaging has emerged as a viable method to measure amyloid burden in the human brain and relate it to neurodegenerative diseases. This article reviews what amyloid imaging has taught us about PDD and DLB. Current data suggest that brain amyloid deposition tends to be more marked in DLB, yet contributes to cognitive impairment in both DLB and PD. These results are broadly consistent with neuropathology and CSF studies. β-Amyloid may interact synergistically with other pathological processes in PD and DLB to contribute to cognitive impairment. [ABSTRACT FROM AUTHOR]

BackgroundAlzheimer’s disease (AD) is a degenerated condition of the brain where memory loss is fully depleted for elderly individual. Efficient machine learning methods are accessible, producing low classification accuracy since single modality features are being evaluated. In this paper, the multimodal approach is developed and execution of comprehensive validation for structural atrophy through Magnetic Resonance Imaging decreases metabolism through Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), and accumulation of amyloid plaques through Pittsburgh compound B (PiB-PET), as well as cognitive assessment for identifying the early onset of AD. It has been stated that additional information from multiple image modalities would ameliorate the classification accuracy while diagnosing early AD. The novel classifier, Adaptive Hyperparameter Tuning Random Forest Ensemble Classifier (HPT-RFE), is proposed for three binary classifications. In this classifier, the tunning of hyperparameters is automated for computing the best features while constructing the optimum size of Random Forest. The advantage of using the classifier is computationally much faster when compared with Support Vector Machine, Naïve Bayes, K-Nearest Neighbour and Artificial Neural Network. Simulation results show that the performance of the Adaptive HPT-RFE classifier has been regarded as best among all binary classifications in the ADNI dataset. For AD versus Normal Control (NC) binary classification, 100% accuracy, sensitivity, and specificity have been achieved, whereas the accuracy of 91% and 100% specificity for NC versus Mild Cognitive Impairment (MCI) classification and 95% accuracy, 100% specificity, 80% sensitivity for AD versus MCI classification are compared with four state-of-the-art techniques. [ABSTRACT FROM AUTHOR]

The devastating effects of the still incurable Alzheimer's disease (AD) project an ever increasing shadow of burden on the health care system and society in general. In this ominous context, amyloid (Aβ) imaging is considered by many of utmost importance for progress towards earlier AD diagnosis and for potential development of effective therapeutic interventions. Amyloid imaging positron emission tomography procedures offer the opportunity for accurate mapping and quantification of amyloid-Aβ neuroaggregate deposition in the living brain of AD patients. This review analyzes the perceived value of current Aβ imaging probes and their clinical utilization and, based on amyloid imaging results, offers a hypothesis on the effects of amyloid deposition on the biology of AD and its progression. It also analyzes lingering questions permeating the field of amyloid imaging on the apparent contradictions between imaging results and known neuropathology brain regional deposition of Aβ aggregates. As a result, the review also discusses literature evidence as to whether brain Aβ deposition is truly visualized and measured with these amyloid imaging agents, which would have significant implications in the understanding of the biological AD cascade and in the monitoring of therapeutic interventions with these surrogate Aβ markers. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to validate the feasibility of a voxel-based analysis of in vivo amyloid-β positron emission tomography (PET) imaging studies in transgenic mouse models of Alzheimer's disease. Procedures: We performed [C]PiB PET imaging in 20 APP/PS1 mice and 16 age-matched controls, and histologically determined the individual amyloid-β plaque load. Using SPM software, we performed a voxel-based group comparison plus a regression analysis between PiB retention and actual plaque load, both thresholded at p < 0.05. In addition, we carried out an individual ROI analysis in every animal. Results: The automated voxel-based group comparison allowed us to identify voxels with significantly increased PiB retention in the cortical and hippocampal regions in transgenic animals compared to controls. The voxel-based regression analysis revealed a significant association between this signal increase and the actual cerebral plaque load. The validity of these results was corroborated by the individual ROI-based analysis. Conclusions: Voxel-based analysis of in vivo amyloid-β PET imaging studies in mouse models of Alzheimer's disease is feasible and allows studying the PiB retention patterns in whole brain maps. Furthermore, the selected approach in our study also allowed us to establish a quantitative relation between tracer retention and actual plaque pathology in the brain in a voxel-wise manner. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined Aβ pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer's disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(−)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(−) case, Aβ plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, Aβ plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(−) case had low levels of [H-3]PiB binding (<100 pmol/g) and Aβ1-42 (<500 pmol/g) concentration except in the frontal cortex where Aβ1-42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800-1,700 pmol/g). In several cortical regions of the [C-11]PiB(−) case, Aβ1-40 levels were within the range of cortical Aβ1-40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of Aβ1-42 and Aβ1-40 in the [C-11]PiB(+), and with Aβ1-42 only in the [C-11]PiB(−) case. The low ratios of [H-3]PiB binding levels to Aβ concentrations and 6-CN-PiB to Aβ plaque loads in the [C-11]PiB(−) case indicate that Aβ pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Aβ concentration and [H-3]PiB binding levels required to produce a positive [C-11]PiB PET signal. [ABSTRACT FROM AUTHOR]

Purpose: Astrocytosis is an important feature of the neuropathology of Alzheimer's disease (AD), yet there is currently no way of detecting this phenomenon in vivo. Methods: In this study we examine the retention of the positron emission tomography (PET) tracer C- L-deuteriodeprenyl (DED), thought to bind activated astrocytes, in 9 patients with moderate to severe AD compared with 11 healthy controls. As a measure of amyloid load, C-labelled Pittsburgh Compound B (PIB) retention was determined. Results: Results show a significantly higher C- L-DED retention in the frontal (35.1% increase, p = 0.001), parietal (35.2%, p = 0.001), temporal (30.9%, p = 0.0001) and medial temporal lobes (22.3%, p = 0.001) in AD compared to healthy controls after blood flow correction. DED retention in the sensorimotor and occipital cortices, and in white matter and subcortical structures, did not differ between groups. There was a moderate but statistically significant ( r = 0.492, p = 0.01) correlation between DED and PIB retention values. Conclusion: Our conclusion is that DED may serve as an in vivo marker for astrocytosis in AD, providing a window into intermediate processes between amyloidosis and neuronal loss and a means of monitoring immunotherapy. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate amyloid deposition in posterior cortical atrophy (PCA), using both cerebrospinal fluid (CSF) biomarker analysis and amyloid imaging. Five PCA patients, selected based on their neuropsychological profile and atrophic changes in posterior regions on MRI, underwent CSF analysis. CSF amyloid-beta 1-42, total tau, and phosphorylated tau at threonine 181 levels were determined. They also had positron emission tomography (PET) with Pittsburgh Compound B ([C]PIB). [C]PIB ratio images were assessed with visual, regional and voxel-based analyses and compared to eight typical Alzheimer's disease (AD) patients and eight controls. The biological profile in the five PCA patients, resulting from CSF and [C]PIB images analysis, was consistent with AD. Individual comparisons of PCA patients' [C]PIB images with the AD group with Statistical Parametric Mapping (SPM) revealed a distinctive posterior uptake in four out of the five patients showing increased amyloid deposition in occipital, temporal, and/or parietal regions. ROI group analysis showed a tendency for higher amyloid deposition in occipital and temporal regions. However, this pattern was not found with SPM group analysis when the global level of [C]PIB uptake was used as a covariate. Our results indicate that amyloid burden can be demonstrated in vivo in PCA suggesting a diagnosis of AD. PCA patients may present a higher global amyloid load than AD that was not related to age at onset, disease severity, disease duration, or educational level in our study. Combined CSF and PET biomarkers seem helpful for in vivo diagnosis of this focal syndrome with underlying AD pathology. [ABSTRACT FROM AUTHOR]

In order to evaluate the role of positron emission tomography (PET) with N-methyl-[C]-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole, also known as Pittsburgh compound B (PIB), in the early diagnosis of Alzheimer's disease (AD). Clinical data were collected, and PIB PET cerebral imaging was performed in patients with AD ( n = 6), mild cognitive impairment (MCI) ( n = 7), and elderly, mentally normal controls (NCs) ( n = 7). PET images of the subjects were then analyzed. Visual analysis showed that the radioactivity clearance rate in AD patients was significantly different from that found in the NC group. Furthermore, the radioactivity clearance rate 45 min after PIB injection was significantly lower than the NC group. Images from the MCI group presented heterogeneous results, overlapping with those from both the AD and NC groups. Statistical analysis showed that the radioactivity clearance rate during 5-45 min post-injection was significantly lower in the AD group (41-77%) than the control group (75-81%) ( P > 0.05) and the MCI group (59-77%). The radioactivity clearance rate in the bilateral parietal lobes, frontal, temporal, and right occipital lobes, and the bilateral corpora striata in MCI group were lower than that in control group ( P < 0.05). PIB PET brain imaging can differentiate early AD patients from NCs and may have certain value in identifying patients progressing to MCI. [ABSTRACT FROM AUTHOR]

Imaging techniques for in vivo visualization of cerebral amyloid using positron emission tomography (PET) have been tested in clinical trails over the past 5 years. Based on a selected overview of the literature including our own studies the various radiopharmaceuticals are presented and the current status of research on the validity of amyloid PET imaging as well as its suitability for early and differential diagnosis of Alzheimer’s disease (AD) are described. The findings available up to now support the validity of amyloid PET imaging and suggest a possible benefit in differential diagnosis. However, there are as yet no studies with large sample sizes. The possible use for the early diagnosis of AD should be viewed critically, particularly due to the lack of treatment options. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to assess the test-retest variability of [11C]PIB studies in patients with Alzheimer's disease (AD) and healthy controls using several tracer kinetic models and to assess the suitability of the cerebellum as reference tissue. Methods [11C]PIB studies with arterial sampling were performed in eight AD patients and eight healthy controls. Retest scans were performed in six controls and six AD patients. Data were analysed using plasma input and reference tissue models, together with simple ratios. Results Test-retest variability was best (?3%) for SRTM2, a parametric method based on the simplified reference tissue model. Highest values (?10%) were found for plasma input models. Cerebellar VT values did not differ significantly between AD and controls. Conclusion Parametric SRTM2 with the cerebellum as reference tissue is the method of choice for quantitative analysis of [11C]PIB PET studies. [ABSTRACT FROM AUTHOR]