CENTILOID SCALE IN PRACTICE: EFFECT OF DIFFERENT SUVR REFERENCE REGIONS AND COMPARISON OF CENTILOID CUT-OFFS

Abstract

Centiloid (CL) conversion aligns amyloid PET measures across tracers1. A CL pipeline converts PET measures to their PiB equivalent and linearly transforms them onto a scale anchored by calibrated means of young controls (YC) and Alzheimer's disease (AD) subjects. We evaluated the impact of the choice in reference region and compared positivity cut-offs for FDA-approved amyloid tracers. Calibration datasets were processed via Bioclinica (BC) SUVR method with whole-cerebellum (WC) and subcortical white matter (SWM) reference regions. FreeSurfer MRI segmentation was used to calculate SUVR from co-registered, motion-corrected, averaged, smoothed PET. Correlation coefficient (R2) from linear regression between published SUVR and BC-SUVR was used to evaluate reliability. If R2 was >0.7, BC-method was considered well-correlated and linear regression between BC-SUVR and published CL was used. Standard of truth SUVR (SOT-SUVR)2,3 cut-offs were converted to CLs and compared to BC-SUVR cut-offs defined as 3 SD above YC CL mean. Standard and BC-SUVRs strongly correlated for WC (Florbetapir R2=0.96, Florbetaben R2=0.98, Flutemetamol R2=0.98). SWM yielded weaker correlations that still met the reliability criterion (Florbetapir R2=0.72, Florbetaben R2=0.88, Flutemetamol R2=0.91). Mean WC-CL in YC was 0.4±9.8 for Florbetapir, -2.0±5.4 for Florbetaben and -1.6±7.4 for Flutemetamol versus published CL values of 1.8±10.8, -0.3±6.8 and -1.0±7.2 respectively, yielding variance ratios of 0.91, 0.79 and 1.03. Mean WC-CL in AD was 53.7±51.7 for Florbetapir, 68.1±54.2 for Florbetaben, and 51.2±49.4 for Flutemetamol versus published CL values of 56.2±55.2, 64.8±56 and 51.6±50.3 respectively, yielding variance ratios of 0.94, 0.97 and 0.98. SOT-SUVR cut-off of 1.112 for Florbetapir converted to 25 CL, Florbetaben 1.453 converted to 62 CL and Flutemetamol 1.202 converted to 37 CL. 3 SD above YC CL mean led to BC-SUVR cut-offs of 30 for Florbetapir, 14 for Florbetaben, and 21 for Flutemetamol. Bioclinica's pipeline produced results concordant with the standard Centiloid method. The whole cerebellum was a more suitable reference region for Centiloid conversion. Centiloids align tracers on a linear scale and therefore tracer related differences are still noticeable. Positivity cut-offs differ among tracers even after Centiloid conversion.