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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, Ki, 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 Ki 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 Ki 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 Ki for the four super regions including cerebellum, frontal cortex, hippocampus, and striatum indicated no significant differences.
Highlights
Noninvasive determination of blood input function from dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) (Table 1) images of rodents including mice and rats has been challenging
Several image-derived methods have been developed over the last several years for noninvasive determination of the blood input function
One such method is the hybrid method (9) that relies on image-derived sampling from the left ventricular blood pool (LVBP) at the early time points due to the rapid change in FDG metabolism and invasive arterial or venous blood sampling at the late time points
Summary
Noninvasive determination of blood input function from dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) (Table 1) images of rodents including mice and rats has been challenging. Recent work from our laboratory has optimized a dual-output model for the myocardial tissue and the LVBP in a three-compartment kinetic model to simultaneously estimate model-corrected blood input function (MCIF) and the kinetic model parameters with SP and PV corrections to compute the rate of myocardial FDG uptake, Ki, from dynamic FDG PET images of control BL/6 mouse hearts in vivo (2). This model was adapted to compute myocardial Ki from total-body FDG PET images of control Wistar–Kyoto (WKY) and experimental spontaneously hypertensive rats (SHR) in vivo (4)
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