Indirect oxygen-17 magnetic resonance imaging of cerebral blood flow and oxidative metabolism

17O, a stable isotope of oxygen with a spin of 5/2, is utilized as a 1H-MRI contrast agent for measurement of absolute cerebral blood flow (CBF), relative tumor blood flow (TBF), and Cerebral Metabolic Rate of Oxygen (CMRO2). Quantitative, high-resolution mapping of H217O is achieved with fast spin echo (FSE) based T1ρ-weighted MRI, which may be implemented readily on any clinical MRI scanner. Strategies are derived and employed for (1) quantitation of absolute H217O tracer concentration from a ratio of high and low frequency spin-locked T1ρ images and (2) mapping CBF without requiring transformation of the T1ρ signal to H 217O tracer concentration. Absolute CBF is mapped in the rat brain at an in-plane resolution of 0.4 mm x 0.8 mm within a 5-min tracer washout time. Relative TBF is measured in subcutaneous RIF-1 tumors in C3H mice by monitoring the uptake of H217O with a resolution of 0.16 mm x 0.31 mm x 3 mm in 13 seconds. At this resolution, tumor heterogeneity with respect to blood flow is clearly visible. T 1ρ-weighted 1H-MRI detection of H2 17O produced via metabolic reduction of inhaled 17O 2 is also demonstrated herein for the first time. 17O 2 is delivered to rats via a specially designed closed respiration circuit that greatly conserves this expensive gas and is conducive to simple scale-up for human use. Quantitative mapping of metabolically produced H2 17O via 1H T1ρ-weighted MRI is validated by direct 17O-magnetic resonance spectroscopy. From the first minute time course of metabolically produced H217O, CMRO2 is estimated to be 2.10 ± 0.44 μmol/g/min (n = 4). Additionally, the possibility of non-enriched oxygen acting as a brain contrast agent for T1ρ imaging is explored. MRI and near-infrared spectroscopy data together suggest that both T2-weighted FSE and FSE-based T1ρ-weighted MRI show oxygen-induced signal changes in the rat brain due to significant sensitivity to deoxyhemoglobin