Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data

TLDR

The distribution volume ratio (DVR), a linear function of receptor availability, is widely used in imaging studies and is defined as the ratio of the distribution volume of a receptor‑containing region to that of a nonreceptor region, typically requiring an arterial input function. The authors propose a graphical method for determining DVR without blood sampling. The method approximates the plasma integral using data from a nonreceptor region with an average tissue‑to‑plasma efflux constant k₂, and was evaluated on PET data from 20 [¹⁵C]raclopride and 8 [¹¹C]d‑threo‑methylphenidate subjects, with initial blood sampling needed to estimate k₂ and test applicability, while in some cases the b₂ term may be neglected if the BG/CB ratio stabilizes. The blood‑sampling‑free method produced DVR estimates virtually identical to the plasma‑based method, with average differences of –0.11 % for raclopride and 0.46 % for dMP, and yielded concordant DVR images, demonstrating equivalent performance for the two ligands.

Abstract

The distribution volume ratio (DVR), which is a linear function of receptor availability, is widely used as a model parameter in imaging studies. The DVR corresponds to the ratio of the DV of a receptor-containing region to a nonreceptor region and generally requires the measurement of an arterial input function. Here we propose a graphical method for determining the DVR that does not require blood sampling. This method uses data from a nonreceptor region with an average tissue-to-plasma efflux constant k 2 to approximate the plasma integral. Data from positron emission tomography studies with [ 15 C]raclopride (n = 20) and [ 11 C] d-threo-methylphenidate ([ 11 C]dMP) (n = 8) in which plasma data were taken and used to compare results from two graphical methods, one that uses plasma data and one that does not. k 2 was 0.163 and 0.051 min −1 for [ 11 C]raclopride and [ 11 C]dMP, respectively. Results from both methods were very similar, and the average percentage difference between the methods was −0.11% for [ 11 C]raclopride and 0.46% for [ 11 C]dMP for DVR of basal ganglia (BG) to cerebellum (CB). Good agreement between the two methods was also achieved for DVR images created by both methods. This technique provides an alternative method of analysis not requiring blood sampling that gives equivalent results for the two ligands studied. It requires initial studies with blood sampling to determine the average kinetic constant and to test applicability. In some cases, it may be possible to neglect the b̅ 2 term if the BG/CB ratio becomes reasonably constant for a sufficiently long period of time over the course of the experiment.