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

TLDR

The study develops and applies two linearized reference tissue models to generate parametric images of binding potential and relative delivery for [11C]DASB PET imaging of serotonin transporters in human brain. The authors modified the multilinear reference tissue model (MRTM0) to MRTM, estimating cerebellar clearance rate k′₂, then fixed k′₂ to create MRTM2, and compared BP and R₁ estimates from MRTM and MRTM2 with nonlinear models (SRTM, SRTM2, 1TKA) on simulated and real data. MRTM2 produced BP estimates with 1–4 % bias and 2–3× lower variability than MRTM or SRTM, matched SRTM2 and 1TKA, and achieved R₁ bias <0.3 % with markedly reduced noise, enabling rapid, reliable parametric imaging for human [11C]DASB PET studies.

Abstract

The authors developed and applied two new linearized reference tissue models for parametric images of binding potential ( BP) and relative delivery ( R 1 ) for [ 11 C]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 R 1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [ 11 C]DASB data. MRTM gave k′ 2 estimates with little bias (&lt;1%) and small variability (&lt;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 R 1 bias &lt;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 [ 11 C]DASB positron emission tomography studies.