TR&D 2

Principal Investigator: John Detre, M.D.

This TR&D focuses on the use of MRI to study tissue function, and builds upon almost two decades of work using arterial spin labeling (ASL) to measure tissue perfusion. Blood flow is a critical pathophysiological parameter and disorders of blood flow are responsible for a large proportion of medical morbidity. Noninvasive imaging of blood flow is also a promising biomarker with a broad range of applications in biomedicine. While blood flow is the key parameter in the evaluation of vascular disorders, blood flow is also an increasingly important parameter in evaluating neoplastic disease and particularly the effects of anti-angiogenesis therapies. Finally, in the brain and other organs, changes in blood flow are coupled to changes in regional metabolism, allowing blood flow to be used as a biomarker for normal tissue function. The ASL method was initially conceived by this Regional Resource, and continues to provide opportunities for technology development and translation to clinical applications. ASL perfusion MRI remains one of the few MRI contrast mechanisms for which the physiological and biological significance is well understood.

Technical developments in ASL, many of which were pioneered under this RR, have resulted in a ten-fold increase in the sensitivity of ASL over the past decade. Collaborative research performed under this RR has also demonstrated many of the translational applications of ASL that have been published to date. While the recent availability of a clinical ASL “product” will undoubtedly lead to a dramatic expansion of its use in clinical care, there remain further opportunities for developing ASL methods and applications. Because of the complementary benefits of increased signal-to-noise and T1 prolongation with increasing magnetic field strength, ASL is expected to benefit heavily from extension to experimental systems operating at ultra-high fields of 7 Tesla or higher, where another 3-4-fold increase in sensitivity is theoretically possible. Development of 7T ASL for use in humans is the first aim of the next project period. This should allow not only better and more reliable images of blood flow, but also provide sufficient sensitivity to more carefully evaluate the biological and biophysical parameters that influence measured signal changes, as proposed in Aim 2.

A shortcoming of MRI technologies is that they require costly instrumentation that can only be used sporadically in individual patients, and entails logistical considerations due to the MRI environment and its location in a Department of Radiology. In contrast, optical methods for measuring tissue blood flow and metabolism are much more portable and are compatible with more frequent or even continuous monitoring at the patient’s bedside. Accordingly, another thrust of our overall research in functional imaging is to try to combine these complementary modalities for simultaneous and sequential use. These efforts comprise Aim 3 of our program, and focus primarily on cross-validation of a Diffuse Correlation Spectroscopy, a novel approach for optical measurement of tissue blood flow.

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