A comprehensive valvular heart disease assessment with stress cardiac MRI

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Project Summary/Abstract Mitral valve regurgitation (MR) is a growing public health concern, and with an aging population, its prevalence is expected to rise steeply. For MR diagnosis and severity assessment, echocardiographic techniques have long been the standard of care. Assessment based on such techniques, however, has limitations, both in terms of technical challenges and treatment recommendations. As a result, optimal management of MR, especially determining the timing of surgery, remains complex and stands to benefit from tools that provide quantitative and comprehensive characterization of MR. The overall goal of this project is to develop and validate a stress cardiovascular MRI protocol that can lead to a more definitive treatment plan for MR patients. Cardiovascular MRI (CMR) is a well-established imaging technique that provides the most comprehensive evaluation of the cardiovascular system. The reproducibility of CMR-based flow quantification has been shown to be superior to that of echocardiography. Despite these advantages, the additive clinical value of CMR for MR patients has not been established. More recently, evidence has emerged that CMR-based assessment has better predictive power for clinical outcomes for MR patients and thus could play a central role in determining management plans for such patients. Existing CMR techniques, however, have significant limitations, precluding their use in routine clinical care. For example, the flow quantification using traditional 2D phase- contrast MRI (PC-MRI) is sensitive to the placement of the imaging plane, cannot measure the transvalvular flow directly, requires breath-holding, and is susceptible to irregular cardiac rhythm. Recently, 4D flow imaging, due to its volumetric coverage and three-directional encoding, has gained significant interest, but acquisition for 4D flow imaging using existing protocols can be prohibitively long, especially for whole-heart coverage. Also, existing 4D flow imaging protocols only perform imaging under resting conditions, which cannot fully characterize functional impairment that is only unmasked under stress testing. In this work, we will develop and validate a comprehensive CMR protocol that (i) provides ferumoxytol- enhanced 4D flow imaging with whole-heart coverage, (ii) requires minimal planning from the MRI technologist, (iii) is performed in clinically feasible acquisition time, (iv) does not require breath-holds or regular cardiac rhythm, (v) does not require navigator gating, (vi) allows imaging during exercise stress, exposing functional impairment, and (vii) additionally provides cardiac function quantification to explain and interpret stress-induced functional impairment observed in MR patients. In Aims 1 and 2, we will develop and optimize the protocol. In Aims 3 and 4, we will validate the accuracy and reproducibility of the protocol in 55 healthy subjects and 55 patients diagnosed with MR. We hypothesize that the developed protocol leads to a more reliable assessment of MR than possible with TTE alone and set the stage for larger clinical studies where the power of CMR parameters to predict clinical outcomes is demonstrated.