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Item Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies(Elsevier, 2019-02-22) Su, Yi; Flores, Shaney; Wang, Guoqiao; Hornbeck, Russ C.; Speidel, Benjamin; Joseph-Mathurin, Nelly; Vlassenko, Andrei G.; Gordon, Brian A.; Koeppe, Robert A.; Klunk, William E.; Clifford, R. Jack, Jr.; Farlow, Martin R.; Salloway, Stephen; Snider, Barbara J.; Berman, Sarah B.; Roberson, Erik D.; Broschi, Jared; Jimenez-Velazques, Ivonne; van Dyck, Christopher H.; Galasko, Douglas; Yuan, Shauna H.; Jayadev, Suman; Honig, Lawrence S.; Gauthier, Serge; Hsiung, Ging-Yuek R.; Masellis, Mario; Brooks, William S.; Fulham, Michael; Clarnette, Roger; Masters, Colin L.; Wallon, David; Hannequin, Didier; Dubois, Bruno; Pariente, Jeremie; Sanchez-Valle, Raquel; Mummery, Catherine; Ringman, John M.; Bottlaender, Michel; Klein, Gregory; Milosavljevic-Ristic, Smiljana; McDade, Eric; Xiong, Chengjie; Morris, John C.; Bateman, Randall J.; Benzinger, Tammie L.S.; Neurology, School of MedicineIntroduction: Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods: Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally. Results: Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion: Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.Item Partial Volume Correction in Quantitative Amyloid Imaging.(Elsevier, 2015-02-15) Su, Yi; Blazey, Tyler M.; Snyder, Abraham Z.; Raichle, Marcus E.; Marcus, Daniel S.; Ances, Beau M.; Bateman, Randall J.; Cairns, Nigel J.; Aldea, Patricia; Cash, Lisa; Christensen, Jon J.; Friedrichsen, Karl; Hornbeck, Russ C.; Farrar, Angela M.; Owen, Christopher J.; Mayeux, Richard; Brickman, Adam M.; Klunk, William; Price, Julie C.; Thompson, Paul M.; Ghetti, Bernardino; Saykin, Andrew J.; Sperling, Reisa A.; Johnson, Keith A.; Schofield, Peter R.; Buckles, Virginia; Morris, John C.; Benzinger, Tammie LS; Department of Pathology & Laboratory Medicine, IU School of MedicineAmyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition.Item Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease(Elsevier, 2018-09-27) Joseph-Mathurin, Nelly; Su, Yi; Blazey, Tyler M.; Jasielec, Mateusz; Vlassenko, Andrei; Friedrichsen, Karl; Gordon, Brian A.; Hornbeck, Russ C.; Cash, Lisa; Ances, Beau M.; Veale, Thomas; Cash, David M.; Brickman, Adam M.; Buckles, Virginia; Cairns, Nigel J.; Cruchaga, Carlos; Goate, Alison; Jack, Clifford R., Jr.; Karch, Celeste; Klunk, William; Koeppe, Robert A.; Marcus, Daniel S.; Mayeux, Richard; McDade, Eric; Noble, James M.; Ringman, John; Saykin, Andrew J.; Thompson, Paul M.; Xiong, Chengjie; Morris, John C.; Bateman, Randall J.; Benzinger, Tammie L. S.; Dominantly Inherited Alzheimer Network; Radiology and Imaging Sciences, School of MedicineIntroduction: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure.