Reduced Transit-Time Sensitivity in Noninvasive Magnetic Resonance Imaging of Human Cerebral Blood Flow

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Abstract
Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.