Feasibility of Longitudinal Brain PET with Real-Time Arterial Input Function in Rats

• Published in: Molecular imaging and biology 2021-06, Vol.23 (3), p.350-360
• Main Authors: Rey-Bretal, David, Moscoso, Alexis, Gómez-Lado, Noemí, Fernández-Ferreiro, Anxo, Silva-Rodríguez, Jesús, Ruibal, Álvaro, Aguiar, Pablo
• Format: Article
• Language: English
• Subjects: Animals; Arteries - diagnostic imaging; Arteriovenous Shunt, Surgical; Bias; Blood Glucose - analysis; Brain; Brain - blood supply; Brain - diagnostic imaging; Bypasses; Cerebrovascular Circulation; Constants; Failure rates; Feasibility; Feasibility Studies; Fluorodeoxyglucose F18 - pharmacology; Imaging; Kinetics; Longitudinal studies; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Metabolic rate; Neuroimaging - methods; Pets; Positron emission tomography; Positron-Emission Tomography - methods; Radiology; Rate constants; Rats; Rats, Sprague-Dawley; Real time; Reproducibility; Reproducibility of Results; Research Article; Shunts; Surgery
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-020-01556-y

Purpose Preclinical dynamic brain PET studies remain hampered by the limitations related to the measurement of the arterial input function (AIF). In this regard, the use of an arterial-venous shunt is a promising method for the generation of real-time AIFs, but its application in longitudinal studies is still impeded by the cumbersome surgeries and high failure rates. We studied the feasibility and reproducibility of double arterial-venous shunt strategies for conducting longitudinal PET studies with real-time AIFs in rats. Procedures We studied the feasibility of double arterial-venous shunts in rats in the right/left inguinal region and evaluated inter-animal and intra-animal AIF reproducibilities. Image-derived input function (IDIF) was also obtained for comparison. Dynamic brain FDG PET studies were conducted to estimate kinetic constants and Cerebral Metabolic Rate of Glucose (CMR glc ) obtained from standard 2-tissue compartment (2TCM) and Patlak analysis. Results We showed that longitudinal AIFs from double arterial-venous shunts can be obtained with very high success rate of the surgeries (88 %). Our results provided highly reproducible AIF measurements with low inter-animal variabilities (11 %) and intra-animal variabilities (5–10 %) that were included into the kinetic models, such that longitudinal rate constants and CMR glc can be efficiently estimated without bias associated to the double shunt. Our results indicated that longitudinal IDIF can be also generated without bias along time but showing higher intra-animal uncertainties. Conclusions We have demonstrated the feasibility and high reproducibility of conducting longitudinal AIF measurements and consequently accurate kinetic modeling using arterial shunt method.