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BINDING OF PITTSBURGH COMPOUND B TO BOTH NORMAL AND ABNORMAL WHITE MATTER IN ELDERLY COGNITIVELY NORMAL CONTROL

      Background: The amyloid imaging agent, Pittsburgh Compound B (PiB), binds with high affinity to β-amyloid (Aβ) in the brain and it is well established that PiB also shows non-specific retention in white matter (WM). However, little is known about retention of PiB in areas of white matter hyperintensities (WMH), abnormalities commonly seen in older adults. Further, WMH are hypothesized to be related to both cognitive dysfunction and Aβ deposition. The goal of the present study was to explore PiB retention in both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals.
      Methods: Cognitively normal elderly (n=64; 86.5±2.6 years) who had a FLAIR-MRI, PiB-PET(SUVR 50-70, cerebellum reference) and visual WMH score were included in this analysis. Two ROI analyses were applied: (1) ROIs of standardized dimensions were placed over “typical” areas of periventricular WMH caps on all subjects, regardless of WMH burden or size. (2) Subject-specific maps of NAWM and WMH were created using C++ and ITK, these maps were then co-registered with the PiB-PET and mean SUVR values were calculated in these NAWM and WMH ROI.
      Results: PiB retention was significantly reduced in the “typical-WMH” ROIs of subjects with high WMH compared to subjects with low WMH (see figure below). Additionally, in subjects with high WMH, there was significantly lower PiB retention in subject-specific ROIs of WMH compared to NAWM, this was not observed in subjects with low WMH, likely because of the absence of WMH in this group.
      Conclusions: These data suggest that white matter in areas of WMH may have different binding characteristics to PiB than does normal WM. Further exploration of this phenomenon may lead to insights about the molecular basis of this non-specific interaction.