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

Abstract

Quantitative total-body PET imaging of blood flow can be performed with freely diffusible flow radiotracers such as ¹⁵O-water and ¹¹C-butanol, but their short half-lives necessitate close access to a cyclotron. Past efforts to measure blood flow with the widely available radiotracer ¹⁸F-fluorodeoxyglucose (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 kinetic modeling to assess total-body blood flow based on deriving the vascular transit time of ¹⁸F-FDG and conducted a pilot comparison study against a ¹¹C-butanol reference.

Methods: The first two minutes of dynamic PET scans were reconstructed at high temporal resolution (60×1 s, 30×2 s) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate ( $K_1$ ) as a surrogate of blood flow, our method directly estimates blood flow using a distributed kinetic model (adiabatic approximation to the tissue homogeneity model; AATH). To validate our ¹⁸F-FDG measurements of blood flow against a flow radiotracer, we analyzed total-body dynamic PET images of six human participants scanned with both ¹⁸F-FDG and ¹¹C-butanol. An additional thirty-four total-body dynamic ¹⁸F-FDG PET scans of healthy participants were analyzed for comparison against literature 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 by 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 R=0.955, p<0.001; linear regression y=0.973x-0.012), 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 literature ranges (e.g., healthy cohort average: 0.51±0.12 ml/min/cm³ in the cerebral cortex and 2.03±0.64 ml/min/cm³ in the lungs, respectively). High temporal resolution (1 to 2 s) was critical to enabling AATH modeling over standard compartment modeling.

Conclusions: Total-body blood flow imaging was feasible using early-dynamic ¹⁸F-FDG PET with high-temporal resolution kinetic modeling. Combined with standard ¹⁸F-FDG PET methods, this method may enable efficient single-tracer flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience.

Keywords: Blood flow/perfusion imaging; Distributed kinetic modeling; High-temporal resolution dynamic imaging; Total-body PET; Tracer kinetic modeling.