Model Corrected Blood Input Function to Compute Cerebral FDG Uptake Rates From Dynamic Total-Body PET Images of Rats in vivo

Abstract

Recently, we developed a three-compartment dual-output model that incorporates spillover (SP) and partial volume (PV) corrections to simultaneously estimate the kinetic parameters and model-corrected blood input function (MCIF) from dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) images of mouse heart in vivo. In this study, we further optimized this model and utilized the estimated MCIF to compute cerebral FDG uptake rates, K _i , from dynamic total-body FDG PET images of control Wistar-Kyoto (WKY) rats and compared to those derived from arterial blood sampling in vivo. Dynamic FDG PET scans of WKY rats (n = 5), fasted for 6 h, were performed using the Albira Si Trimodal PET/SPECT/CT imager for 60 min. Arterial blood samples were collected for the entire imaging duration and then fitted to a seven-parameter function. The 60-min list mode PET data, corrected for attenuation, scatter, randoms, and decay, were reconstructed into 23 time bins. A 15-parameter dual-output model with SP and PV corrections was optimized with two cost functions to compute MCIF. A four-parameter compartment model was then used to compute cerebral Ki. The computed area under the curve (AUC) and K _i were compared to that derived from arterial blood samples. Experimental and computed AUCs were 1,893.53 ± 195.39 kBq min/cc and 1,792.65 ± 155.84 kBq min/cc, respectively (p = 0.76). Bland-Altman analysis of experimental vs. computed K _i for 35 cerebral regions in WKY rats revealed a mean difference of 0.0029 min^-1 (~13.5%). Direct (AUC) and indirect (Ki) comparisons of model computations with arterial blood sampling were performed in WKY rats. AUC and the downstream cerebral FDG uptake rates compared well with that obtained using arterial blood samples. Experimental vs. computed cerebral K _i for the four super regions including cerebellum, frontal cortex, hippocampus, and striatum indicated no significant differences.

Keywords: Wistar–Kyoto rat; arterial blood sampling; cerebral fluoro-2-deoxy-D-glucose uptake rate; dual output model; dynamic fluoro-2-deoxy-D-glucose positron emission tomography.

Figure 1

Arterial Blood Sampling in Wistar–Kyoto (WKY) rats. (A) Sketch showing catheterization of the carotid artery. (B) Picture of a WKY rat during the experimental procedure. (C) Arterial Blood Sample measurements averaged over n = 5 WKY rats with standard error as a function of image acquisition time.

Figure 2

Time-resolved total-body 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) images. (A–E) Example PET/CT rendering cut across showing uptake in Wistar–Kyoto (WKY) rat myocardium and brain over a period of 60 min.

Figure 3

Peak fits with objective function O₂(p). (A) Peak blood fit with and without the second objective function, O₂(p) Equation (2). (B) Peak tissue fit with and without O₂(p).

Figure 4

Model-corrected blood input function (MCIF). (A) Representative 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) images with regions of interest drawn in the myocardium and (B) left ventricular blood in the last time frame. (C) Dual-output model (Model IDIF, Model Myo) fitted to image-derived blood (PET IDIF) and myocardium (PET Myo) time activity curves (TACs) to generate the MCIF. For comparison, blood samples derived from arterial blood sampling are shown.

Figure 5

Computed cerebral 2-[18F] fluoro-2-deoxy-D-glucose (FDG) uptake rates in Wistar–Kyoto (WKY) rats. (A) Example brain PET image of WKY rat co-registered onto W. Schiffer T2 rat brain atlas showing 35 volumes of interest. (B) Bland–Altman plot comparing computed model and experimental Ki. (C) Example brain PET image of WKY rat co-registered onto W. Schiffer T2 rat brain atlas combining the 35 volumes of interest (VOIs) into four regions of interest. (D) Four-parameter compartment model fitted to time activity curves (TACs) derived from the dynamic PET data for the regions indicated in panel C. (E) Recovery coefficient (RC) of all the 58 VOIs derived from the atlas for an example WKY rat. (F) Comparison between experimental and computed K_i for the cerebellum, striatum, hippocampus, and frontal cortex.