Affiliations: Janssen Research & Development LLC, Pharmaceutical Companies of Johnson & Johnson, USA
Correspondence:
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Correspondence to: Volha Tryputsen, Janssen Research & Development, LLC, 1000 US Highway 202, Raritan, NJ 08869, USA. Tel.: +1 908 927 5320; Fax: +1 908 927 3782; E-mail: vtryputs@its.jnj.com.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Abstract: Background:Pittsburgh Compound B (PiB) positron emission tomography (PET) neuroimaging is a powerful research tool to characterize amyloid evolution in the brain. Quantification of amyloid load critically depends on (i) the choice of a reference region (RR) and (ii) on the selection of regions of interest (ROIs) to derive the standard uptake value ratios (SUVRs). Objective:To evaluate the stability, i.e., negligible amyloid accumulation over time, of different RRs, and the performance of different PiB summary measures defined by selected ROIs and RRs for their sensitivity to detecting longitudinal change in amyloid burden. Methods:To evaluate RRs, cross-sectional and longitudinal analyses of focal regional and composite measures of amyloid accumulation were carried out on the standardized PiB-PET regional data for cerebellar grey matter (CER), subcortical white matter (SWM), and pons (PON). RRs and candidate composite SUVR measures were further evaluated to select regions and develop novel composites, using standardized 2-year change from baseline. Results:Longitudinal trajectories of PiB4—average of anterior cingulate (ACG), frontal cortex (FRC), parietal cortex, and precuneus—demonstrated marked variability and small change from baseline when normalized to CER, larger changes and less variability when normalized to SWM, which was further enhanced for the composite in PON-normalized settings. Novel composite PiB3, comprised of the average SUVRs of lateral temporal cortex, ACG, and FRC was created. Conclusion:PON and SWM appeared to be more stable RRs than the CER. PiB3 showed compelling sample size reduction and gains in power calculations for clinical trials over conventional PiB4 composite.
