Non-invasive hemodynamic and biomechanic imaging methods for early risk prediction in aortic dissection

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PROJECT SUMMARY/ABSTRACT Aortic dissection (AD) is a disease characterized by sudden tearing of the inner layers of the aortic wall creating a false lumen (FL) channeling aortic blood flow. The vast majority of acute AD patients survive into the chronic phase, although long-term outcomes are poor with about 50% of patients experiencing aorta-related mortality or requiring surgical repair by 10 years. A major contributor to poor long-term outcomes is growth of the FL. Thoracic endovascular aortic repair (TEVAR) is a minimally invasive surgical therapy which can halt FL growth and reduce AD mortality; however, this treatment comes with cost, risk of procedural complications, and is less effective over time owing to increased tissue stiffness. Accurate prediction of disease trajectory at early phases is limited with current metrics but is highly desirable as this would allow TEVAR to be targeted to high-risk patients in a timely manner, sparing those at lower risk from potentially unnecessary procedures. Current methods for estimating risk in AD are largely based on anatomic metrics (e.g., aortic diameter), which poorly capture functional aspects of AD. To overcome these limitations, we propose to apply advanced imaging techniques, namely 4D Flow magnetic resonance imaging (MRI) and 4D computed tomography angiography (CTA), to characterize and quantify functional processes such as FL pressure and FL wall stiffness, which elude current imaging approches and have been implicated as important factors in predicting long-term behavior of AD. We hypothesize that assessments of these functional metrics will, improve our prediction of false lumen growth rate (FLGR) compared to standard anatomic metrics. We plan to prospectively recruit patients with either uncomplicated type B (n=30) or surgically repaired type A (n=45) aortic dissection to undergo baseline 4D Flow and 4D CTA imaging in the subacute period (1-3 months post-dissection) as well as follow-up studies at 1- and 2-years post-dissection, with the primary outcome being FLGR. To achieve these goals, the Aims of this proposal are: 1) Identify baseline hemodynamic and biomechanical metrics in the subacute period of AD that predict FL growth rate over time. FL pressure will be quantified from 4D Flow MRI using indirect and direct methods based on physics-based image analysis, with regional FL wall stiffness quantified by merging FL pressure with cyclic aortic wall deformation by 4D CT; 2) Determine the trajectories of functional metrics over time that best predict progressive FL growth. Longitudinal changes in pressure and wall stiffness between baseline and 1- and 2-year follow-up scans will be assessed to identify patients who achieve a new equilibrium versus those who continue to progress; 3) Develop a clinical assessment tool to predict risk of progressive FL growth combining functional metrics, anatomic parameters and patient characteristics with a focus on simplicity and accuracy for dissection-type specific prediction of the FLGR at the earliest possible time point. This work seeks to shift the paradigm of AD assessment from pure anatomic characterization by integrating functional imaging biomarkers to provide accurate predictions of disease trajectory and allow for optimal determination of surgical candidacy and timing.