Most radiotracers for PET imaging are utilized to assess their end-product properties, for instance for assessing glucose metabolism with [F18]FDG. The intermediate molecular transport processes of a radiotracer across a vascular barrier (e.g., blood-brain barrier) are much less explored. However, the transport steps of radiotracers may provide rich information on health and disease. A major focus of our lab is to develop PET methods to measure the molecular transport properties of a radiotracer, which may then be combined with their regular use to enable single-tracer multiparametric imaging. The enabling techniques include (a) dynamic PET imaging using high-performance scanners (e.g., EXPLORER total-body PET) or advanced image reconstruction methods (e.g., the kernel methods Wang & Qi 2015, Wang 2019, Li & Wang 2022, Li et al 2023), and (b) tracer kinetic modeling that allows more accurate quantification of the transport rates of a radiotracer in different organs.
Since 2016, we have been focusing on quantifying the blood-to-tissue delivery rate (K1) of radiotracers. We developed methods for K1 quantification in various organs, including the liver (Wang et al 2018, Zuo et al. 2019 ), lungs (Wang Y et al. 2023, Wang Y et al 2024), heart (Zuo et al 2020), and brain (Zhu et al 2024). We have successfully applied the K1 imaging method to assess liver inflammation in metabolic dysfunction-associated steatohepatitis (Sarkar et al 2019, Sarkar et al 2021) and to measure myocardial blood flow in patients with heart disease (Zuo et al 2021), using the widely available [F18]FDG.
One limitation of the K1 method is that the estimates often represent a combination of blood flow and tracer-specific transport rates, making it difficult to understand the underlying biology. To address this, we have developed high-temporal resolution imaging and modeling methods that allow for the simultaneous estimation of blood flow and tracer-specific transport rates from a single scan (Chung et al 2024a; Chung et al 2024b; Wang et al. 2019; Wang et al. 2018). This capability also further facilitates the measurement of the molecular permeability of radiotracers across the vascular barrier, as demonstrated in our recent work (Chung et al 2024a).
Funding Support:
The projects related to this research direction are supported by the NIH R01 Award R01 EB033435 from NIBIB and R01 DK124803 from NIDDK.
Selected Journal Papers:
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- Chung KJ, Chaudhari AJ, Nardo L, Jones T, Chen MS, Badawi RD, Cherry SR, Wang GB.
Quantitative total-body imaging of blood flow with high temporal resolution early dynamic 18F-Fluorodeoxyglucose PET kinetic modeling.
[Preprint: medRxiv doi: https://doi.org/10.1101/2024.08.30.24312867] - Wang Y, Abdelhafez YG, Spencer BA, Verma R, Parikh M, Stollenwerk N, Nardo L, Jones T, Badawi RD, Cherry SR, and Wang GB.
High-Temporal Resolution Kinetic Modeling of Lung Tumors with Dual-Blood Input Function Using Total-Body Dynamic PET.
Journal of Nuclear Medicine, 65 (5) 714-721, 2024. - Wang Y, Nardo L, Spencer BA, Abdelhafez Y, Li EJ, Omidvari N, Chaudhari AJ, Badawi RD, Jones T, Cherry SR, and Wang GB.
Total-Body Multiparametric PET Quantification of 18F-FDG Delivery and Metabolism in the Study of COVID-19 Recovery.
Journal of Nuclear Medicine, , 2023. - Sarkar S, Matsukuma KE, Spencer B, Chen S, Olson KA, Badawi RD, Corwin MT, Wang GB.
Dynamic positron emission tomography/computed tomography imaging correlate of non-alcoholic steatohepatitis.
Clinical Gastroenterology and Hepatology, 19(11): 2441-2443, 2021. - Zuo Y, Lopez JE, Smith T, Foster CC, Carson RE, Badawi RD, Wang GB.
Multiparametric Cardiac 18F-FDG PET in Humans: Pilot Comparison of FDG Delivery Rate with 82Rb Myocardial Blood Flow.
Physics in Medicine and Biology, 66(15): 155015, July 2021. - Zuo Y, Badawi RD, Foster CC, Smith T, López JE, Wang GB.
Multiparametric cardiac 18F-FDG PET in humans: kinetic model selection and identifiability analysis.
IEEE Transactions on Radiation in Plasma and Medical Sciences, 4(6): 759 – 767, 2020. - Sarkar S, Corwin MT, Olson KA, Stewart S, Liu CH, Badawi RD, and Wang GB.
Pilot study to diagnose non-alcoholic steatohepatitis with dynamic 18F-fluorodeoxyglucose positron emission tomography.
American Journal of Roentgenology, 212(3): 529-537, 2019. - , , , , Dynamic PET of human liver inflammation: impact of kinetic modeling with optimization-derived dual-blood input function.
Physics in Medicine and Biology, 63(15): 155004 (14pp), 2018.
Selected Conference Presentations: