Voxel-based NK1 Receptor Occupancy Measurements with [18F]SPA-RQ and Positron Emission Tomography: A Procedure for Assessing Errors from Image Reconstruction and Physiological Modeling

Abstract

This study shows that even this kind of complicated receptor study can be statistically evaluated. The reconstruction methods had an effect on the variance in the voxel-based receptor occupancy calculation. The model calculation methods influenced the average bias. The test method was found useful in assessing the methodological sources of systematic and random error in receptor occupancy estimation with PET.

Direct 4D parametric imaging for linearized models of reversibly binding PET tracers using generalized AB-EM reconstruction

“…However, the Logan method is known to result in a noise-induced negative bias in the estimates of DV (Abi-Dargham et al , 2000; Slifstein and Laruelle, 2000; Logan et al , 2001; Wallius et al , 2007; Gunn et al , 2002; Fujimura et al , 2006). This is related to the fact that this formulation involves a complex dependence on the concentration term C j ( t ), which for our purposes would also much complicate the 4D reconstruction formulation.…”

“…where DV j and B j are the slope and intercept parameters at a voxel j, and C p and C j are the plasma and target tissue tracer concentrations, respectively, which are sampled at a discrete number of times t, in accordance with the imaging protocol. However, the Logan method is known to result in a noise-induced negative bias in the estimates of DV (Abi-Dargham et al 2000, Slifstein and Laruelle 2000, Logan et al 2001, Wallius et al 2007, Gunn et al 2002, Fujimura et al 2006. This is related to the fact that this formulation involves a complex dependence on the concentration term C j (t), which for our purposes would also much complicate the 4D reconstruction formulation.…”

A consistent and efficient graphical analysis method to improve the quantification of reversible tracer binding in radioligand receptor dynamic PET studies

“…However, the application of the Logan plot is limited by the noise level of target tissue tracer concentration C(t). There is noise-induced negative bias in the estimates of DV T and binding potential (BP) ( = DVR −1) from the Logan plot, and the underestimation in the estimates from the Logan plot is dependent on both the noise level and magnitude of tissue concentration C(t) (Abi-Dargham et al, 2000; Fujimura et al, 2006; Gunn et al, 2002; Slifstein and Laruelle, 2000; Logan et al, 2001; Wallius et al, 2007). The noise-induced underestimation can result in reduced contrasts in the estimates of BP among targeted tissues, and reduced statistical power to discriminate populations of interest by a specific tissue BP (Zhou et al, 2008).…”

Relative Equilibrium Plot Improves Graphical Analysis and Allows Bias Correction of Standardized Uptake Value Ratio in Quantitative 11C-PiB PET Studies

“…In contrast, a commonly used Logan plot demonstrates inherent negative bias which is attributed to noise and the target tissue tracer concentration (18–22). The linearized methods, particularly multilinear reference tissue model (MRTM) (23) provide similar estimates of DVR as a simplified reference tissue model (SRTM) (9) yet with much higher computational efficacy.…”

“…The linearized methods, particularly multilinear reference tissue model (MRTM) (23) provide similar estimates of DVR as a simplified reference tissue model (SRTM) (9) yet with much higher computational efficacy. At the pixel level, PET measurements have high noise and thus underestimation of DVR occurs with both graphical (19) and linearized methods (10, 18, 24). While all of these approaches are associated with bias, bias consistency across clinical groups has not been extensively explored in [ 11 C]PiB studies although bias may be one of the limiting factors for the application of the simplified quantitative methods to this tracer.…”