Linearized reference tissue parametric imaging methods: Application to [¹¹C]DASB positron emission tomography studies of the serotonin transporter in human brain

The authors developed and applied two new linearized reference tissue models for parametric images of binding potential (BP) and relative delivery (R₁) for [¹¹C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTM_O) was modified (MRTM) and used to estimate a clearance rate (k′₂) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k′₂. The resulting BP and R₁ estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [ ¹¹C]DASB data. MRTM gave k′₂ estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTM_O from 12-70% to 1-4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R₁ bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [ ¹¹C]DASB positron emission tomography studies.