Novel MR imaging and analysis of the dynamic microvascular network

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The small blood vessel (microvascular) network is a highway connecting all the cells in our body, controlling blood pressure and allowing the exchange of nutrients and wastes. Even more sophisticated than an urban roadway network, the microvascular network can adaptively increase or reduce "speed limits" and the number of open "roads" and "lanes" to ensure the most efficient transport of sufficient goods to where it is needed in the body. Platforms that open a window on the microvasculature and enable detailed characterization in vivo are absolutely critical to our understanding of how mature microvessels are regulated and how new ones grow during development and repair. Existing whole-body imaging technologies such as magnetic resonance imaging (MRI), CT, and ultrasound can assess blood flow but not vasomodulation (change in vessel diameter), a much more complex phenomenon whereby local blood flow is adjusted in response to altered physiological demands. A technology gap currently exists, because just as we cannot say a two-lane highway can prevent traffic congestion at all times, we also cannot judge the performance of the microvascular network on perfusion status alone. In this NSERC application, we propose a research program to fill this gap by building on our long-standing expertise in microvascular MRI to augment the capabilities of a transformative platform we recently developed for assessing vasomodulation - the first ever dynamic MRI technology for perturbing and measuring vasomodulation in deep tissue. We will generalize our technology to the whole body by tackling the two remaining organs that are challenging for different reasons: the rapidly beating heart (challenge: motion) and skeletal muscle (challenge: low perfusion). Specifically, we will design novel acquisitions for near real-time cardiac MRI of the heart, develop mathematical models to sensitize measurements in low perfusion settings, and integrate these capabilities to understand how blood flow is adjusted synchronously in different organs to maintain normal blood pressure. Collectively, this work will advance the state-of-the-art in quantitative physiological imaging of the microvascular network, creating new technologies with broad applications in fundamental physiology studies, diagnostic medical imaging, and novel tissue engineering and regeneration paradigms. Furthermore, the proposed research offers exceptional opportunities for training graduate and undergraduate students in the core natural sciences and engineering (electrical engineering, mathematics, physiology) within an interdisciplinary context. The scientific knowledge and skills they acquire will enable them to make long-term impact and to lead their own initiatives at the interface of engineering and the life sciences.