Reference tissue is used in some methods such as simplified reference tissue methods, reference Logan plot, and pseudo-equilibrium method. Although true equilibrium is never achieved and kinetic analysis is preferable to quantify amyloid load with amyloid PET, pseudo-equilibrium method is the simplest method in the world, which does not require arterial blood sampling or PET scanner-occupying dynamic scan. Its index, SUVR has been widely used as a substitute for distribution volume ratio (DVR). Reference tissue is required to have the same K1/k2 as the target region and not to have the specific binds to amyloid. Cerebellar cortex fulfils almost the requirement and it has been used as a reference region. However, some studies with Florbetapir use white matter as a reference region and show the advantage in longitudinal study over cerebellar reference region. Apparently, white matter does not fulfil the requirement of the reference tissue. What makes the advantage of white matter reference region? Decrease in K1 caused by CBF change has been shown to affect SUVR. One study with Florbetaben showed cerebellar reference region is the best for longitudinal studies. What is the difference? Acquisition time? To discover the source of the advantage of white matter reference region, we have executed simulations.
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