Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologiccomparison

Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentr ation (so-called partial volume effect or PVE) resulting in systematic erro rs in estimating quantitative physiologic parameters. The authors have form ulated four mathematical models that describe the dynamic behavior of a fre ely diffusible tracer ((H2O)-O-15) in a region of interest (ROI) incorporat ing estimates of regional tissue flow that are independent of PVE. The curr ent study was intended to evaluate the feasibility of these models and to e stablish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV (H2O)-O-15 two times (n = 3) or three times (n = 2) in a row, Two ROIs were drawn on structural magnetic resonance imaging ( MRI) scans and projected onto the PET images in which regional CBF values a nd the water perfusable tissue fraction for the cortical gray matter tissue thence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the g ray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. A ll models tested in the current study yielded PVE-corrected regional CBF va lues (approximately 0.8 mL.min(-1).g(-1) for models with a term for gray ma tter tissue and 0.5 mL.min(-1).g(-1) for models with a term for a mixture o f gray matter and white matter tissues). These values were greater than tho se obtained from ROIs tracing the gray matter cortex using conventional (H2 O)-O-15 autoradiography (approximately 0.40 mL.min(-1).g(-1)). Among the fo ur models, configurations that included two parallel tissue compartments de monstrated better results with regards to the agreement of tissue time-acti vity curve and the Akaike's Information Criteria. Error sensitivity analysi s suggested the model that fits three parameters of the gray matter CBF, th e gray matter fraction, and the white matter fraction with fixed white matt er CBF as the most reliable and suitable for estimating the gray matter CBF . Reproducibility with this model was 11% for estimating the gray matter CB F. The volume of gray matter tissue can also be estimated using this model and was significantly correlated with the results from the stereologic anal ysis. However, values were significantly smaller compared with those measur ed by stereologic analysis by 40%, which can not be explained by the method ologic errors. In conclusion, the partial volume correction was essential i n quantitation of regional CBF. The method presented in this article provid ed the PVE-corrected regional CBF in the cortical gray matter tissue. This study also suggests that further studies are required before using MRI deri ved anatomic information for PVE correction in PET.