Hybrid image and blood sampling input function for quantification of small animal dynamic PET data

Abstract

We describe and validate a hybrid image and blood sampling (HIBS) method to derive the input function for quantification of microPET mice data. The HIBS algorithm derives the peak of the input function from the image, which is corrected for recovery, while the tail is derived from 5 to 6 optimally placed blood sampling points. A Bezier interpolation algorithm is used to link the rightmost image peak data point to the leftmost blood sampling point. To assess the performance of HIBS, 4 mice underwent 60-min microPET imaging sessions following a 0.40-0.50-mCi bolus administration of 18FDG. In total, 21 blood samples (blood-sampled plasma time-activity curve, bsPTAC) were obtained throughout the imaging session to compare against the proposed HIBS method. MicroPET images were reconstructed using filtered back projection with a zoom of 2.75 on the heart. Volumetric regions of interest (ROIs) were composed by drawing circular ROIs 3 pixels in diameter on 3-4 transverse planes of the left ventricle. Performance was characterized by kinetic simulations in terms of bias in parameter estimates when bsPTAC and HIBS are used as input functions. The peak of the bsPTAC curve was distorted in comparison to the HIBS-derived curve due to temporal limitations and delay in blood sampling, which affected the rates of bidirectional exchange between plasma and tissue. The results highlight limitations in using bsPTAC. The HIBS method, however, yields consistent results, and thus, is a substitute for bsPTAC.

Figure 1

An illustration of the hybrid image- and blood-sampling (HIBS) method with a Bezier linker. Bezier control points are indicated by p₀, p₁, p₂, and p₃. Control point p₀ corresponds to the rightmost image peak data point; p₃ corresponds to and the leftmost blood sampling point; and control points p₂ and p₃ are determined by calculating the intersection of a linear polynomial through the peak and extrapolation of the blood samples as illustrated by the dashed (blue) lines. The resulting linker is depicted in gray. Note that the image peak data is corrected for recovery prior to the application of HIBS.

Figure 2

A representative example of reconstructed PTAC with HIBS. Letter labels in each panel correspond to mouse labels in Table 1. The LV ROI, blood samples and Bezier linker are indicated in the Figures A1 and B1 (note that the term “blood tail” refers to blood samples beyond 1-minute). For ease of visualization, the first 10-minutes are shown with an inset for the 60-minute (in log-scale) of imaging session in panel A2 and B2. Note that time points beyond 1-minute would match blood samples. In panels C and D we display the first minute of blood sampling and image acquisition for mice C and D.