Table 3.

Characteristics of different reference regions in amyloid PET quantification

Optional reference region	Advantages	Disadvantages
CGM	Free of Aβ Same non-displaceable activity as the target area	The susceptibility to noise such as the nonspecific signal from the cerebellar peduncles and specific binding from adjacent cortical tissues Low sensitivity for signal due to its location at the edge of the scanner’s field of view Artifacts via truncation or attenuation correction of images due to the low position Amyloid deposition in cerebellum in patients with gene mutations and at advance stages
WC	Same as CGM Higher signal intensity and less susceptibility to noise compared to CGM Include tissue less vulnerable to edge and truncation effects compared to CGM	Almost the same as CGM
Pons	Same as CGM	Small size Sensitivity to head motion The poor performance of many normalization routines The susceptibility to scatter and truncation effects due to its location at the outer extremes of the field of view of an axial PET scanner
WC + B	Same as WC	Same as WC and Pons
SWM	Large region Locate approximately the same as target VOI in the axial field of view to reduce variability Represent the average uptake value of signal intensity, potentially leading to less noise More resistant to small degrees of misregistration during image quantification	Atrophy and vascular lesions White matter could play a specific role in amyloid compound uptake Affect by the combined effects of fibrillar Aβ and partial-volume averaging
PERSI-WM	The same as SWM PVE correction Individual based non-specific binding voxels with a lower intensity than other contaminated voxels	Same as SWM Individual MRI is required

CGM cerebellar gray matter, WC whole cerebellum, WC + B whole cerebellum plus brainstem, SWM subcortical white matter, PERSI-WM parametric estimation of reference signal intensity-white matter