Diffusion-weighted imaging (DWI) is a magnetic resonance imaging method that shows great promise for early detection of a number of forms of central nervous system (CNS) injury, including stroke, trauma, and status epilepticus. At the present time, the mechanism(s) underlying the rapid change in contrast in diffusion-weighted images after CNS injury is poorly understood. As a first step to understanding these mechanisms, two classes of experiments are proposed to evaluate changes in water apparent diffusion coefficient (ADC) in the intra-and extracellular spaces in association with rat models of stroke or status epilepticus. The first utilizes NMR-detectable, compartment-specific probes to indirectly detect changes in motion in either the intra- or extracellular space in association with CNS injury. Probes of the intracellular space will be 133Cs+, in situ generated 2-fluorodeoxyglucose-6-phosphate (with 19F detection), 23Na+, and endogenous 1H metabolites. Probes of the extracellular space will be 3-aminopropylphosphonate (with 31P detection), 2-fluorodeoxyglucose-6-phosphate (with 19F detection), and 23Na+. The second class of experiments will involve infusion of relaxation contrast agent (gadoteridol) into the lateral cerebral ventricle of rats, from which it spreads throughout the extracellular space and greatly reduces the T1 relaxation time constant of extracellular water. Once this is accomplished, it is possible to design NMR pulse sequences which permit acquisition of ADC data which is heavily weighted to signal from either intra- or extracellular compartment. For these studies, compartment-specific changes in water ADC will be correlated with histologic assessment of infarct severity. In a third class of experiments, the possibility that some of the ADC decrease associated with stroke is due to underestimates of ADC caused by paramagnetic effects of deoxyhemoglobin will be examined. Taken together, these studies are designed to begin unraveling the compartment-specific ADC changes responsible for DWI contrast in an effort to permit more precise use of this promising imaging modality.
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