Quantitative Total-Body Imaging of Blood Flow with High-Temporal-Resolution Early Dynamic 18F-FDG PET Kinetic Modeling

Abstract

Past efforts to measure blood flow with the widely available radiotracer ¹⁸F-FDG were limited to tissues with high ¹⁸F-FDG extraction fraction. In this study, we developed an early dynamic ¹⁸F-FDG PET method with high-temporal-resolution (HTR) kinetic modeling to assess total-body blood flow based on deriving the vascular phase of ¹⁸F-FDG transit and conducted a pilot comparison study against a ¹¹C-butanol flow-tracer reference. Methods: The first 2 min of dynamic PET scans were reconstructed at HTR (60 x 1 s/frame, 30 x 2 s/frame) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate as a surrogate of blood flow, our method directly estimated blood flow using a distributed kinetic model (adiabatic approximation to tissue homogeneity [AATH] model). To validate our ¹⁸F-FDG measurements of blood flow against a reference flow-specific radiotracer, we analyzed total-body dynamic PET images of 6 human participants scanned with both ¹⁸F-FDG and ¹¹C-butanol. An additional 34 total-body dynamic ¹⁸F-FDG PET images of healthy participants were analyzed for comparison against published blood-flow ranges. Regional blood flow was estimated across the body, and total-body parametric imaging of blood flow was conducted for visual assessment. AATH and standard compartment model fitting was compared using the Akaike information criterion at different temporal resolutions. Results: ¹⁸F-FDG blood flow was in quantitative agreement with flow measured from ¹¹C-butanol across same-subject regional measurements (Pearson correlation coefficient, 0.955; P < 0.001; linear regression slope and intercept, 0.973 and –0.012, respectively), which was visually corroborated by total-body blood-flow parametric imaging. Our method resolved a wide range of blood-flow values across the body in broad agreement with published ranges (e.g., healthy cohort values of 0.51 ± 0.12 mL/min/cm³ in the cerebral cortex and 2.03 ± 0.64 mL/min/cm³ in the lungs). HTR (1–2 s/frame) was required for AATH modeling. Conclusion: Total-body blood-flow imaging was feasible using early dynamic ¹⁸F-FDG PET with HTR kinetic modeling. This method may be combined with standard ¹⁸F-FDG PET methods to enable efficient single-tracer multiparametric flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience.