A hybrid deconvolution approach for estimation of in vivo non-displaceable binding for brain PET targets without a reference region

Abstract

Background and aimEstimation of a PET tracer’s non-displaceable distribution volume (VND) is required for quantification of specific binding to its target of interest. VND is generally assumed to be comparable brain-wide and is determined either from a reference region devoid of the target, often not available for many tracers and targets, or by imaging each subject before and after blocking the target with another molecule that has high affinity for the target, which is cumbersome and involves additional radiation exposure. Here we propose, and validate for the tracers [11C]DASB and [11C]CUMI-101, a new data-driven hybrid deconvolution approach (HYDECA) that determines VND at the individual level without requiring either a reference region or a blocking study.MethodsHYDECA requires the tracer metabolite-corrected concentration curve in blood plasma and uses a singular value decomposition to estimate the impulse response function across several brain regions from measured time activity curves. HYDECA decomposes each region’s impulse response function into the sum of a parametric non-displaceable component, which is a function of VND, assumed common across regions, and a nonparametric specific component. These two components differentially contribute to each impulse response function. Different regions show different contributions of the two components, and HYDECA examines data across regions to find a suitable common VND. HYDECA implementation requires determination of two tuning parameters, and we propose two strategies for objectively selecting these parameters for a given tracer: using data from blocking studies, and realistic simulations of the tracer. Using available test-retest data, we compare HYDECA estimates of VND and binding potentials to those obtained based on VND estimated using a purported reference region.ResultsFor [11C]DASB and [11C]CUMI-101, we find that regardless of the strategy used to optimize the tuning parameters, HYDECA provides considerably less biased estimates of VND than those obtained, as is commonly done, using a non-ideal reference region. HYDECA test-retest reproducibility is comparable to that obtained using a VND determined from a non-ideal reference region, when considering the binding potentials BPP and BPND.ConclusionsHYDECA can provide subject-specific estimates of VND without requiring a blocking study for tracers and targets for which a valid reference region does not exist.

Kappa opioid receptor binding in major depression: A pilot study

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Serotonin transporter binding in major depressive disorder: impact of serotonin system anatomy

“…A metabolite-corrected arterial plasma input function was created as described 28 , and was inputted into empirical Bayesian estimation in graphical analysis (EBEGA) 38 , a quantification approach designed to handle noise found in PET time activity curves at the voxel level 38 , to obtain whole-brain, voxel-wise tracer volume of distribution (V T ) maps. Binding potential BP P maps were then created by subtracting brain-wide estimates of the radiotracer non-displaceable distribution volume (V ND ), obtained in each participant using the hybrid deconvolution approach (HYDECA) 39 , without having to assume any reference region.…”

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“…For cases where the imaging targets are distributed throughout the brain, such that ROI REF cannot be readily identified (e.g., TSPO), compartmental modelling may be desirable for a subset of subjects to validate a simplified pseudo-reference-region approach. A data-driven hybrid deconvolution approach (HYDECA) was recently proposed for the global determination of V ND using singular value decomposition to estimate the impulse-response function for several regional time-activity curves (TACs), but knowledge of the metabolite-corrected arterial IF was still required (Zanderigo et al 2017). Accordingly, image-derived input functions (IDIFs) remain long-sought-after alternatives, as discussed below.…”