Reference Tissue-based Kinetic Modeling
The SRTM2 was used for the voxel-wise [11C]CFT kinetic analysis21, 26, 27, which generated two parametric images: R1 (the ratio between the transport rate constants of target and reference tissues) and DVR (distribution volume ratio between the target and reference tissues). The R1 represents the relative transporter rate constant of tracer from vascular space to the target organs or brain regions, whereas DVR reflects the tracer specific binding to DAT. The occipital lobe region lacking DAT distribution was selected as the reference tissue. A linear regression with spatial constraint algorithm was used to generate parametric images of R1 and DVR21, 28.
To the best of our knowledge, no clinical studies have yet conducted a total-body dynamic [11C]CFT analysis utilizing the voxel-wise SRTM2 method. Thus, we additionally performed the VOI-based one-tissue compartmental modeling (1T2K) with the metabolite-corrected TAC of descending aorta as the input function using PMOD to validate our SRTM2 estimates 28. The tracer transport rate constant (K1) and total distribution volume (VT) as the estimates for early blood perfusion and later tracer density were generated to validate the use of R1 and DVR, respectively.