Brain MRI segmentation is required for quantitative PET analysis, in order to derive regional uptake and calculate uptake ratio relative to reference regions. FreeSurfer has been a popular method but is being supplanted by faster and more robust AI-driven methods. The objective of this work is to confirm that the use of Clario’s novel AI segmentation method, whose impact was assessed towards various MRI endpoints, is also valid in the context of PET quantification. 507 subjects from ADNI were selected, including normal controls, subjective memory complainers, early/late MCI and AD subjects. Besides, 210 were selected with available test/re-test data. For each, a pair of good quality 3DT1 MRI and Amyloid PET scans were available. 3DT1 data were segmented with both FreeSurfer v6 (FS) and Clario’s AI method (AI), and registered to PET space for calculation of Standard Uptake Value (SUV) in a set of cortical regions (frontal, posterior cingulate, lateral parietal and lateral temporal) and reference regions (cerebellar grey and whole cerebellum). SUVR (ratio to reference region) was calculated for both. Results were also converted to Centiloid (CL) units. SUV and SUVR values were compared across segmentation methods via Bland-Altmann plots and correlated with Pearson’s coefficient. The ability to distinguish between disease severity stages was assessed by ROC analysis using global AUC. Finally, classification as amyloid (Aβ) positive or negative was assessed by setting a cut-off of 20.1 CL and looking at Cohen’s Kappa. SUV and SUVR values were highly and significantly correlated between FS and AI methods (r>0.99, p<0.001) and for test/re-test, for all regions investigated, with a difference that did not exceed 0.41% on average (SD<1.38%). Global AUC was comparable for both methods and for test/retest (average gAUC=0.62). Aβ classification was near-perfect across methods (κ=0.98) and between test/retest data (κ FS =0.97, κ AI =0.99). Comparing FreeSurfer and Clario’s AI-based MRI segmentation method, no impact was found on subsequent PET analyses and test/retest performance was equivalent. These results support the use of either method for PET quantification. For future trials, the AI method could either be used as the primary method, or as a back-up when traditional FS segmentation fails.

The accumulation of neurofibrillary tangles contributes to a neurodegenerative cascade toward Alzheimer’s disease. Focal tau deposition may impair signal integrity within a broader network of functionally connected brain regions. 18F-Flortaucipir PET allows visualization of tau pathology in vivo, and functional compensation between Default Mode Network (DMN) subsystems is an fMRI-based biomarker of network failure. We sought to characterize the relationship between network failure in the DMN and tau burden throughout the brain. 620 ADNI3 subject visits with concurrent fMRI and flortaucipir PET scans were selected from the database ( http://adni.loni.ucla.edu ) for analysis. ADNI PET core PVC values referencing inferior cerebellar cortex were used to index SUVR across the entire FreeSurfer parcellation, and the ADNI MRI core Network Failure Quotient (NFQ) was used as a summary metric of fMRI connectivity strength in the DMN. Linear partial correlation coefficients were calculated for NFQ and SUVR in each brain region, controlling for age. Lasso logistic regression also returned penalized maximum-likelihood fitted coefficients for a generalized linear model estimating NFQ from regional SUVR; regions with non-zero coefficients in the sparsest model were included in a composite. A subset of 131 subjects with paired visits at one year follow-up were included in longitudinal analysis. A significant age-corrected association was observed between higher NFQ, reflecting worsening DMN failure, and higher flortaucipir SUVR in Braak 1 (p < 0.02) and meta-temporal composite ROIs (p < 0.03). Age-corrected partial correlations achieved marginal significance (p < 0.05) in bilateral entorhinal, inferior and middle temporal, superior parietal and caudal middle frontal cortices, left posterior cingulate and right isthmus cingulate. Lasso regression revealed a subset of non-zero coefficients including frontal, temporal, cingulate and subcortical brain regions. In the longitudinal analysis, age-corrected baseline tau load in Braak 5/6 and a set of frontoparietal subregions was marginally significantly associated with change in NFQ after 1 year. Functional network failure in the DMN is associated with greater tau burden inside and outside the network. These results suggest the NFQ is a viable fMRI-based biomarker for tau pathophysiology and disease state.

Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure- free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.

Objective Previous positron emission tomography (PET) studies using [C-11]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [C-11]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. Methods We obtained magnetic resonance imaging (MRI) and [C-11]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [C-11]ABP688 nondisplaceable binding potential (BPND) values were averaged across each subfield, and Z-scores were calculated. Subfield [C-11]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [F-18]fluorodeoxyglucose (FDG) uptake in each clinical group. Results MTLE [C-11]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [C-11]ABP688-BPND and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [C-11]ABP688-BPND was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [C-11]ABP688-PET+[F-18]FDG-PET showed no between-group significant difference in [F-18]FDG uptake, whereas CA1-3 [C-11]ABP688-BPND remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21). Significance Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [C-11]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [C-11]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients.

Background: PET imaging of [ 11 C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [ 11 C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [ 11 C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), and 3) Subiculum and manually corrected. Partial volume corrected [ 11 C]ABP688 non-displaceable binding potential (BP ND ) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [ 11 C]ABP688 BP ND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [ 11 C]ABP688 BP ND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure-free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [ 18 F]FDG-PET, CA1-3 [ 11 C]ABP688 BP ND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [ 18 F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [ 11 C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [ 18 F]FDG-negative MTLE patients.

The partial volume effect (PVE), caused by the limited spatial resolution of positron emission tomography (PET), degrades images both qualitatively and quantitatively. Anatomical information provided by magnetic resonance (MR) images has the potential to play an important role in partial volume correction (PVC) methods. Post-reconstruction MR-guided PVC methods typically use segmented MR tissue maps, and further, assume that PET activity distribution is uniform in each region, imposing considerable constraints through anatomical guidance. In this work, we present a post-reconstruction PVC method based on deconvolution with parallel level set (PLS) regularization. We frame the problem as an iterative deconvolution task with PLS regularization that incorporates anatomical information without requiring MR segmentation or assuming uniformity of PET distributions within regions. An efficient algorithm for non-smooth optimization of the objective function (invoking split Bregman framework) is developed so that the proposed method can be feasibly applied to 3D images and produces sharper images compared to PLS method with smooth optimization. The proposed method was evaluated together with several other PVC methods using both realistic simulation experiments based on the BrainWeb phantom as well as in vivo human data. Our proposed method showed enhanced quantitative performance when realistic MR guidance was provided. Further, the proposed method is able to reduce image noise while preserving structure details on in vivo human data, and shows the potential to better differentiate amyloid positive and amyloid negative scans. Overall, our results demonstrate promise to provide superior performance in clinical imaging scenarios.

72 Introduction: Partial volume effects impair the accurate quantification of PET scans, and are important consideration in voxelwise statistical analyses. A number of methods have been proposed for voxelwise partial volume correction (PVC); however, comparison of PVC methods in real data sets is difficult due to the lack of objective criteria. Objectives: develop objective criteria to assess the performance of voxelwise PVC methods and apply these criteria to compare three PVC methods using 15O-H2O brain PET scans. Methods: We used cross-sectional 15O-H2O brain PET data acquired on a GE Advance scanner for 175 participants from the Baltimore Longitudinal Study of Aging to assess the performance of the following voxelwise PVC methods: reblurred Van Cittert (VC) [1], Region-Based Voxelwise (RBV) [2], and Parallel Level Set (PLS) with a non-smooth optimization technique (split Bregman) [3]. Images were reconstructed as a single time frame using filtered backprojection, yielding ~7.5 mm FWHM resolution at the center of the field of view [4]. For each participant, we coregistered their inhomogeneity-corrected and skull-stripped structural MRI with their PET. Anatomical regions were defined on the MRI using a multi-atlas labeling approach [5] and mapped onto the PET using the coregistration result. We used the cerebellar gray matter as the reference region to compute standardized uptake value ratios (SUVR). To aid in the evaluation of the performance of voxelwise PVC methods, we calculated the error in SUVR estimates. Assuming that voxelwise intensities are independent, and that within a given region, they are identically distributed as a normal with mean μ and variance σ2 , a first-order Taylor series expansion of the definition of SUVR yields Var(SUVR)≍(μT/μR)2[σT2/(n μT2) + σR2 / (m μR2)], where n and m are the number of voxels within the target (T) and reference (R) regions, respectively. A lower variance is desirable, since it indicates a smaller error in the SUVR estimate. To assess the performance of voxelwise PVC methods, we used the following criteria: the lowest uncertainty in regional SUVR estimates, given by Var(SUVR), and the greatest negative age association at baseline (after adjusting for sex), given by the number of voxels with statistically significant differences within the cortical gray matter. Results: PLS yielded the lowest Var(SUVR), resulting in a lower uncertainty in regional SUVR compared to not performing PVC, while not affecting the overall SUVR levels (Figure 1). In the voxelwise analysis, PLS yielded the greatest number of statistically significant voxels where older individuals had lower SUVR (Figure 2). Conclusion: PLS can improve statistical analysis by reducing the uncertainty around regional SUVR estimates, and may enable the discovery of effects that would not be considered statistically significant without PVC or other PVC methods. Acknowledgments: This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, and R21 Grant No. AG056142. Figure 1. Swarm and box plots of (A) the expected value of SUVR and (B) square root of the SUVR variance for the right posterior cingulate gyrus. Results were similar in other cortical gray matter regions. None=No PVC, VC=reblurred Van Cittert, RBV=Region-Based Voxelwise, PLS=Parallel Level Set. Figure 2. Normalized histograms of two-sided t-values for the age term in the linear regression model with voxelwise SUVR as outcome (adjusted for sex). Each row corresponds to a different PVC method. Red vertical dashed lines indicate the t-values that correspond to a multiple comparison-corrected (via permutation tests) p

1399 Introduction: PET suffers from spatial resolution limitations and the ensuing partial volume effects (PVE) greatly impact accurate tracer quantification. Partial volume correction (PVC) methods include region-based (ROI) and voxel-based (image) approaches. While PET has commonly involved regional (ROI) assessment of activity concentrations due to individual voxel noise, it can be desirable to obtain actual images obtained with PVC for further inspection and analysis. Methods: While the region-based geometric transfer matrix (GTM) method [1] is widely used for PVC, it has sometimes been toned down for only providing ROI values, and not being able to provide actual images corrected for PVE. At the same time, images corrected for PVE using the GTM-PVC method can be produced following some extra computing steps. We applied our GTM-PVC method [1] to a cohort of cognitively normal volunteers (N=10) and to patients diagnosed with Alzheimer’s disease (N=10), who underwent amyloid load assessment using two different PET tracers ([11C]-PiB, and [18F]-florbetapir). Dynamic PET data were acquired on a GE Advance® scanner, and the last 4 frames from the 70min studies, assumed to be in a steady state, were averaged and used for analysis. MRI data were used to build individual tracer models (Fig. 1) derived from a cloud-based service [2] using multi-atlas segmentation approach [3]. PET simulations were carried out to derive GTM data for each of the 31 regions (VOI) labeled in the tracer model (Fig. 1). Subject-specific MRI-derived ROI templates were built upon thresholding (50%) each volume-of-interest (VOI)’s axial component of the regional spread function [4]. Correction maps derived from the GTM-PVC data were then generated using the concept of apparent recovery coefficient [5] [AR1] and applied to the original PET data to yield PVC images (GTM-PIX, Fig. 2). After applying the GTM-PVC method, corrected ROI values were then compared with the values obtained from application of the same ROI template to the GTM-based pixel (GTM-PIX) images. Results: Regional values obtained from the GTM-PIX method were compared with regional values obtained after GTM-PVC using the same ROI template. Regional activity concentrations from the GTM-PIX PVC method were found to be in excellent agreement with regional values obtained with the GTM-PVC method, typically showing close to one-on-one correlation, with R2 values typically > 0.99 (Fig. 3). Conclusions: We show how easily it is to derive images from the GTM correction method, not requiring any additional input, and that can be very easily implemented following application of the GTM PVC method. This method provides results consistent with those obtained with the GTM-PVC after sampling the GTM-PIX images with the same ROI templates. Acknowledgements: This work was supported in part by R21 grant no. AG056142 from the National Institute on Aging. References: [1] Rousset et al., J Nuc Med (1998); [2] Mori, S. et al., Computing in Science & Engineering (2016); [3] Wang, H. et al., Inf Process Med Imaging (2013); [4] Rousset et al., J Nucl Med (2008); [5] Rousset et al., Comp Med Imag Graph (1993)

To determine the extent of metabotropic glutamate receptor type 5 (mGluR5) network abnormalities associated with focal cortical dysplasia (FCD), we performed graph theoretical analysis of [11C]ABP688 PET binding potentials (BPND), which allows for quantification of mGluR5 availability. Undirected graphs were constructed for the entire cortex in 17 FCD patients and 33 healthy controls using inter-regional similarity of [11C]ABP688 BPND. We assessed group differences in network integration between healthy controls and the ipsilateral and contralateral hemispheres of FCD patients. Compared to healthy controls, FCD patients showed reduced network efficiency and reduced small-world connectivity. The mGluR5 network of FCD patients was also less resilient to targeted removal of high centrality nodes, suggesting a less integrated network organization. In highly efficient hub nodes of FCD patients, we observed a significant negative correlation between local efficiency and duration of epilepsy only in the contralateral hemisphere, suggesting that some nodes may be more vulnerable to persistent epileptic activity. Our study provides the first in vivo evidence for a widespread reduction in cortical mGluR5 network integration in FCD patients. In addition, we find that ongoing epileptic activity may alter chemoarchitectural brain organization resulting in reduced efficiency in distant regions that are essential for network integration.

179 Objectives: We propose and investigate a parallel level set (PLS) method with Bregman iteration, utilizing MRI anatomical information, to guide post-reconstruction enhancement of PET images. We evaluate the proposed method against conventional PLS with Limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm. Methods: PLS is a promising method which can improve quality of PET images with anatomical prior from MRI[1]. By enforcing alignment of gradients between PET and MR images, it incorporates anatomical information into PET images without requiring segmentation. The PLS framework has been successfully implemented with the quasi-Newton L-BFGS algorithm [2]. The Bregman iteration method was originally proposed to solve total variation models [3]. In Bregman iteration, data residual is added back to the original data after every iteration. In our task, after every Bregman iteration, we compute the difference between the reconstructed image and a blurred image acquired by convoluting the post processed image with system PSF. This difference, which contains both noise and fine structure information, is then added back to the reconstructed noisy and blurry image for next iteration. With this procedure, we expect the algorithm could provide more detail and improved quantitative performance compared with the PLS method implemented by the L-BFGS algorithm. For assessment, simulation experiments were conducted using the BrainWeb phantom [4], incorporating realistic resolution blurring as well as 10 noise realizations to generate PET sinograms. For reconstruction, the OSEM algorithm was implemented with 10 subsets and 24 iterations. Reconstructed images were smoothed by a Gaussian filter with FWHM=2.5mm and then fed into the L-BFGS PLS and Bregman iteration PLS methods. We performed 3 Bregman iterations. In each Bregman iteration, the PLS regularized subproblem was solved by L-BFGS with no more than 300 iterations. For the purely L-BFGS PLS method, the number of iterations was set to 900. Mean percentage bias as well as standard deviation were computed in gray matter and white matter. Subsequently, by varying regularization parameters, we obtained bias vs. noise trade-off curves for the two methods. Results: For visual inspection, both methods generated PET images with enhanced quality compared to OSEM reconstructed images. To compare images from L-BFGS PLS and Bregman iteration PLS, we choose images with regularization parameter that generates matched noise level. We noticed Bregman iteration PLS is able to provide more structure details. For quantitative results, PLS with Bregman iteration outperformed L-BFGS PLS by reducing bias by about 12% for gray matter and 13% for white matter at matched noise level with statistical significance (p<0.01 for paired t test). For Bregman iteration PLS, we also observed as regularization parameter decreases, noise increases quickly while bias stops from further decreasing. This is caused by the fact that small regularization parameters fail to penalize noise sufficiently when we add back the residual term. For larger regularization parameters, while images appear blurry after first Bregman iteration, more structure details are extracted from the residual term in later iterations. In addition, larger regularization parameters help suppress noise from the residual term. This results in a relative clean image with important edges preserved. Conclusions: A Bregman iteration PLS method was studied in this work. The method provides more structure details and enhances quantitative performance of PET images compared with the use of conventional L-BFGS PLS method. Acknowledgments: This work was supported by NIH R21 grant AG056142 and the Natural Science Foundation of Guangdong Province, grant 2018A030313366.

We tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D-2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1R and D2R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2R density in the striatum of women with RTT compared to control subjects. 2) PET imaging of mouse striatum similarly demonstrated significant reductions in D2R density of 7-10 week-old hemizygous (Mecp2-null) and heterozygous (HET) mice compared to wild type (WT) mice. With age, the density of D2R declined in WT mice but not HET mice. 3) In contrast, postmortem autoradiography revealed no group differences in the density of D1R and D2R in the caudate and putamen of RTT versus normal control subjects. 4) In humans and in the mouse model, PET revealed only marginal group differences in DAT. The results confirm that dopaminergic dysfunction in WIT is also present in Mecp2-deficient mice and that reductions in D2R more likely explain the impaired ambulation and progressive rigidity observed rather than alterations in DAT.

Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses.

Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [11C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [11C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals.

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.

The primary objectives of this study were to assess the safety of [18F]flutemetamol injection and determine the level of association between the quantitative estimates of brain uptake of [18F]flutemetamol and the quantitative immunohistochemical (IHC) estimates of amyloid levels in cerebral cortex biopsies obtained during shunt placement in patients with normal pressure hydrocephalus (NPH).