Attenuation correction is a notable challenge associated with simultaneous PET/MRI, particularly in neuroimaging, where sharp boundaries between air and bone volumes exist. This leads to concerns regarding the visual and, more specifically, quantitative accuracy of PET reconstructions for data obtained with PET/MRI. Recently developed techniques can synthesize attenuation maps using only MRI data and are likely adequate for clinical use, however, little work has been conducted to assess their suitability for the dynamic PET studies frequently employed in research to derive physiological information such as binding potential of neuroreceptors in a region. At the same time, existing PET/MRI attenuation correction methods are predicated upon synthesizing CT data, which is not ideal, as CT data are acquired with much lower energy photons than PET data and thus do not optimally reflect the PET attenuation map. We trained a convolutional neural network to generate patient-specific transmission data from T1-weighted MRI. Using the trained network, we generated transmission data for a testing set comprising 11 subjects scanned withC-WAY-100635 and 10 subjects scanned with C-DASB. We assessed both static and dynamic reconstructions. For dynamic PET data, we report differences in BPND and BPF forC-WAY-100635 and VT for C-DASB. The mean bias for generated transmission data was -1.06±0.81%. Global biases in static PET uptake were -0.49±1.7%, and -1.52±0.73% for C-WAY-100635 andC-DASB, respectively. Our neural network approach is capable of synthesizing patient-specific transmission data with sufficient accuracy for both static and dynamic PET studies.

Positron emission tomography tracers [C]ABP688 and [F]FPEB target the metabotropic glutamate receptor subtype 5 providing quantification of the brain glutamatergic system in vivo. Previous [C]ABP688 positron emission tomography human test-retest studies indicate that, when performed on the same day, significant binding increases are observed; however, little deviation is reported when scans are >7 days apart. Due to the small cohorts examined previously (eight and five males, respectively), we aimed to replicate the same-day test-retest studies in a larger cohort including both males and females. Results confirmed large within-subject binding differences (ranging from -23% to 108%), suggesting that measurements are greatly affected by study design. We further investigated whether this phenomenon was specific to [C]ABP688. Using [F]FPEB and methodology that accounts for residual radioactivity from the test scan, four subjects were scanned twice on the same day. In these subjects, binding estimates increased between 5% and 39% between scans. Consistent with [C]ABP688, mean absolute test-retest variability was previously reported as <12% when scans were >21 days apart. This replication study and pilot extension to [F]FPEB suggest that observed within-day binding variation may be due to characteristics of mGluR5; for example, diurnal variation in mGluR5 may affect measurement of this receptor.

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in the pathophysiology of mood and anxiety disorders and is a potential treatment target in major depressive disorder (MDD). This study compared brain mGluR5 binding in elderly patients suffering from MDD with that in elderly healthy volunteers using positron emission tomography (PET) and [11C]ABP688. Twenty elderly (mean age: 63.0±6.3) subjects with MDD and twenty-two healthy volunteers in the same age range (mean age: 66.4±7.3) were examined with PET after a single bolus injection of [11C]ABP688, with many receiving arterial sampling. PET images were analyzed on a region of interest and a voxel level to compare mGluR5 binding in the brain between the two groups. Differences in [11C]ABP688 binding between patients with early- and late-onset depression were also assessed. In contrast to a previously published report in a younger cohort, no significant difference in [11C]ABP688 binding was observed between elderly subjects with MDD and healthy volunteers. [11C]ABP688 binding was also similar between subgroups with early- or late-onset depression. We believe this is the first study to examine mGluR5 expression in depression in the elderly. Although future work is required, results suggest potential differences in the pathophysiology of elderly depression versus depression earlier in life.

Introduction The objective of this study was to investigate associations between dementia in World Trade Center (WTC) responders and in vivo volumetric measures of hippocampal subfield volumes in WTC responders at midlife. Methods A sample of 99 WTC responders was divided into dementia and unimpaired groups. Participants underwent structural T1‐weighted magnetic resonance imaging. Volumetric measures included the overall hippocampus and eight subfields. Regression models examined volumetric measure of interest adjusting for confounders including intracranial volume. Results Dementia was associated with smaller hippocampal volume and with reductions across hippocampal subfields. Smaller hippocampal subfield volumes were associated with longer cumulative time worked at the WTC. Domain‐specific cognitive performance was associated with lower volumetric measures across hippocampal subregions. Conclusions This is the first study to investigate hippocampal subfield volumes in a sample of WTC responders at midlife. Selective hippocampal subfield volume reductions suggested abnormal cognition that were associated with WTC exposure duration.