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 (MRTMO) 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 MRTMO 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.

Cerebral serotonin transporter binding is inversely related to body mass index

“…Cerebellum (as defined above) was used as a reference region, representing non-specific binding only. We used a modified reference tissue model designed specifically for quantification of [ 11 C]DASB (MRTM/ MRTM2) as described and evaluated by Ichise et al (2003) using the software PMOD version 2.9, build 2 (PMOD Technologies): A fixed washout constant, designated k2', was calculated for each individual as an average of k2 in caudate, putamen and thalamus relative to cerebellum using MRTM. Subsequently, k2' was inserted into MRTM2 and BP ND was calculated for the VOIs relative to cerebellum.…”

Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

“…Relative [ 18 F]MK-9470 uptake was expressed as SUV values normalized on whole-brain SUV. Parametric D 2 binding index (BI) images, representing D 2 receptor availability, were constructed by reference to the cerebellum using the Ichise multilinear reference tissue model 2 (MRTM2) module in PMOD [28]. Relative regional glucose metabolism was determined by count normalizing [ 18 F]FDG data to the whole-brain uptake.…”

Effects of Citalopram Infusion on the Serotonin Transporter Binding of [11C]DASB in Healthy Controls

“…Furthermore, methods for the fast generation of parametric maps using a cerebellar time-activity curve (TAC) as the input function were presented (Ichise et al, 2003;Kim et al, 2006).…”