The apparent diffusion coefficient (ADC), as measured by diffusion-weighted MRI, has proven useful in the diagnosis and evaluation of ischemic stroke. The ADC of tissue water is reduced by 30-50% following ischemia and provides excellent contrast between normal and affected tissue. Despite its clinical utility, there is no consensus on the biophysical mechanism underlying the reduction in ADC. In this work, a numerical simulation of water diffusion is used to predict the effects of cellular tissue properties on experimentally measured ADC. The model indicates that the biophysical mechanisms responsible for changes in ADC postischemia depend upon the time over which diffusion is measured. At short diffusion times, the ADC is dependent upon the intrinsic intracellular diffusivity, while at longer, clinically relevant diffusion times, the ADC is highly dependent upon the cell volume fraction. The model also predicts that at clinically relevant diffusion times, the 30-50% drop in ADC after ischemia can be accounted for by cell swelling alone when intracellular T(2) is allowed to be shorter than extracellular T(2).
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