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Background  We aim to provide a systematic study of the impact of white matter (WM) spill-in on the calculation of standardized uptake value ratios (SUVRs) on Aβ-negative subjects, and we study the effect of including WM in the reference region as a compensation. In addition, different partial volume correction (PVC) methods are applied and evaluated.    Methods  We evaluated magnetic resonance imaging and  18 F-AV-45 positron emission tomography data from 122 cognitively normal (CN) patients recruited at the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cortex SUVRs were obtained by using the cerebellar grey matter (CGM) (SUVR CGM ) and the whole cerebellum (SUVR WC ) as reference regions. The correlations between the different SUVRs and the WM uptake (WM-SUVR CGM ) were studied in patients, and in a well-controlled framework based on Monte Carlo (MC) simulation. Activity maps for the MC simulation were derived from ADNI patients by using a voxel-wise iterative process (BrainViset). Ten WM uptakes covering the spectrum of WM values obtained from patient data were simulated for different patients. Three different PVC methods were tested (a) the regional voxel-based (RBV), (b) the iterative Yang (iY), and (c) a simplified analytical correction derived from our MC simulation.    Results  WM-SUVR CGM  followed a normal distribution with an average of 1.79 and a standard deviation of 0.243 (13.6%). SUVR CGM  was linearly correlated to WM-SUVR CGM  ( r  = 0.82, linear fit slope = 0.28). SUVR WC  was linearly correlated to WM-SUVR CGM  ( r  = 0.64, linear fit slope = 0.13). Our MC results showed that these correlations are compatible with those produced by isolated spill-in effect (slopes of 0.23 and 0.11). The impact of the spill-in was mitigated by using PVC for SUVR CGM  (slopes of 0.06 and 0.07 for iY and RBV), while SUVR WC  showed a negative correlation with SUVR CGM  after PVC. The proposed analytical correction also reduced the observed correlations when applied to patient data ( r  = 0.27 for SUVR CGM ,  r  = 0.18 for SUVR WC ).    Conclusions  There is a high correlation between WM uptake and the measured SUVR due to spill-in effect, and that this effect is reduced when including WM in the reference region. We also evaluated the performance of PVC, and we proposed an analytical correction that can be applied to preprocessed data.

Spill-in counts in the quantification of 18F-florbetapir on Aβ-negative subjects: the effect of including white matter in the reference region