The use of deuterium oxide (21120) is proposed as a freely diffusible nuclear magnetic resonance (NMR) blood flow and tissue perfusion tracer of potential clinical utility. Deuterium is a stable, nonradiative isotope commercially available as 2H20 at enrichment levels of essentially 100%-i.e., 110 molar equivalent deuterium. This high concentration, together with the short relaxation time of the spin 1 (quadrupole) deuterium nuclide, provides substantial sensitivity for NMR spectroscopy. As a result, when 2H20 is administered in a bolus fashion to a specific tissue or organ in vivo, the deuterium NMR intensity time course can be analyzed, using mathematical models developed by others for radiolabeled tracers, to measure the rate of blood flow and tissue perfusion. Such an application is demonstrated herein at a static magnetic field of 8.5 tesla. Using single-compartment flow modeling, hepatic blood flow and tissue perfusion in fasted (18 hr) male Sprague-Dawley rats was determined to be 61 ± 17 (mean ± SD) ml/100 g per min (n = 5).The measurement of regional blood flow and tissue perfusion provides an important clinical indicator of tissue viability and vascular competency. Nuclear magnetic resonance (NMR) flow measurement techniques, including those based on spin-imaging procedures, that employ observation of the naturally abundant 1H resonance from H20 have been developed (for reviews, see refs. 1-3). These techniques generally rely on the spatial evolution of 1H magnetization after the initial preparation of a nonequilibrium spin-state population distribution. Therefore, magnetic resonance flow measurements are often limited by the lifetime of the nonequilibrium state and, thus, by the water spin-lattice and spin-spin 1H relaxation times. However, such approaches are extremely attractive because of their completely noninvasive nature and their development remains an area of very active investigation (4, 5).Alternatively, as described in the early pioneering work of Kety (6-8), one can introduce an exogenous substance as a blood-flow tracer, usually one containing a radiolabel. Although the administration of the tracer substance introduces an invasive character to the flow measurement, the high sensitivity of nuclear decay detection and the use of radiolabels that decay slowly relative to blood flow result in measurement methods of considerable practical utility (9-11). Importantly, by employing tracer substances that freely diffuse through aqueous spaces (i.e., intracellular, interstitial), a quantification of tissue perfusion is achieved in contrast to a measurement of simply linear or plug flow velocity in large vessels. One such tracer substance that has seen considerable use in combination with positron emission detection is H2150 (12)(13)(14)(15)(16)(17)(18).We propose herein the analogous use of 2H20 as a diffusible blood-flow and tissue-perfusion tracer where deuterium NMR is used to monitor label intensity as a function of time. Deuterium is a nonradiative, naturally abundant (0.0156%), quadr...