Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain

Abstract

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 (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 11C]DASB positron emission tomography studies.