Abstract (PET group: Jean-Claude M. Rwigema, Tae Kim)
Title: Variability of PET-PIB retention measurements due to different scanner
performance in multi-site trials
Introduction
Amyloid- (A) plaque deposition is known as a pathological hallmark of Alzheimer’s
disease (AD). Pittsburgh compound-B (PIB) is a radiotrancer used in positron emission
tomography (PET) that binds to amyloid plaques and is a valuable tool in the
development and evaluation of antiamyloid therapeutics. Such drug development
requires large numbers of research subjects with the concurrent need for large multi-site
trials. The objective of this study was to investigate the variability in PET-based
measures of PIB retention due to site-to-site differences in scanner performance in
comparison to the variability between individual test and retests in the same scanner. The
study presented here is a component of a larger PIB imaging project performed at 3 sites
(Umich, UPitt, WashU). Each site operates the same model PET scanner (Siemens HR+),
but with different versions of the image reconstruction software including different
scatter corrections. Previous phantom studies have shown these software differences, as
opposed to small hardware or acquisition electronic settings, dominate differences in
performance among the 3 scanners.
Materials and methods
For the study component reported here, data acquired at UMich were used. For each
subject (1 control, and 3 with mild cognitive impairment (MCI), a pre-AD condition),
dynamic [11C]PIB data were acquired over a 90-minute period starting at the time of
injection(15 mCi). High resolution MR images were also acquired for anatomical
reference. Each subject was scanned once, and rescanned for comparison. The raw data
were reconstructed at UMich. Using electronic diagnostic parameters obtained from the
UMich scanner, it was also possible to reconstruct the UMich data using the UPitt
software. The result of this process was, for each acquired dataset, two image sets: the
original as reconstructed at UMich, and a second produced as if the data had been
acquired at UPitt. Thus for each subject we have a test/retest comparison and a
“scanner/scanner” comparison. For all image sets, distribution volume ratios (DVR), a
measure of PIB binding, were calculated by Logan analysis for a number of different
regions in the brain.
Results and conclusions
PIB retention from two of MCI subjects showed “AD-like” results, with significant
uptake distributed similarly to that found in subjects with AD. One MCI subject showed
“control-like” behavior with relatively little PIB uptake. The variability of test/retest (=
(test-retest)/test) was 5.4 ± 3.4 % (n = 4). Scanner/scanner DVR variance was
significantly higher than test/retest variance in high PIB uptake areas (high DVR) in
“AD-like” MCI, while such variances were comparable in lower uptake areas in AD-like
subjects and in control and “control-like” MCI where PIB uptake was uniformly low.
Results of this study show that scanner/scanner variability depends on the degree of
regional PIB retention with high levels of uptake showing greater scanner/scanner
variability.