Novel MR imaging and analysis of the dynamic microvascular network

小血管（微血管）网络是连接我们体内所有细胞的高速公路，控制血压并允许营养和废物的交换。甚至比城市道路网络更复杂，微血管网络可以自适应地增加或减少“速度限制”以及开放的“道路”和“车道”的数量，以确保最有效地将足够的货物运输到体内需要的地方。打开微血管窗口并实现体内详细表征的平台对于我们理解成熟微血管如何调节以及新血管在发育和修复过程中如何生长至关重要。现有的全身成像技术，如磁共振成像（MRI），CT和超声可以评估血流，但不能评估血管调节（血管直径的变化），这是一种更为复杂的现象，局部血流可以根据生理需求的变化进行调整。目前存在技术差距，因为正如我们不能说双车道高速公路可以随时防止交通拥堵一样，我们也不能仅根据灌注状态来判断微血管网络的性能。在这个NSERC申请中，我们提出了一个研究计划，通过建立我们在微血管MRI方面的长期专业知识来填补这一空白，以增强我们最近开发的用于评估血管调节的变革性平台的能力-这是第一个用于扰动和测量深部组织血管调节的动态MRI技术。我们将把我们的技术推广到全身，解决剩下的两个因不同原因而具有挑战性的器官：快速跳动的心脏（挑战：运动）和骨骼肌（挑战：低灌注）。具体来说，我们将设计用于心脏近实时心脏MRI的新型采集，开发数学模型以在低灌注设置中敏感测量，并整合这些功能以了解如何在不同器官中同步调整血流以维持正常血压。总的来说，这项工作将推进微血管网络定量生理成像的最新技术，创造在基础生理学研究，诊断医学成像和新型组织工程和再生范例中具有广泛应用的新技术。此外，拟议的研究为培养研究生和本科生在核心自然科学和工程（电气工程，数学，生理学）在跨学科背景下的特殊机会。他们获得的科学知识和技能将使他们能够产生长期影响，并在工程和生命科学的界面上领导自己的举措。

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.