Comprehensive Cardiac Structure-Function Analysis in Heart Transplantation

摘要/摘要 心脏移植(HTX)是一种公认的挽救生命的手术，但与严重的并发症有关。 目前的临床监测算法依赖于频繁的侵入性程序，包括心内膜心肌活检 导管血管造影术。为了解决这些限制，PI开发了非侵入性的全面 心脏核磁共振，它可以量化心肌组织和功能的局部变化。我们的努力集中在 关于HTX的两个主要并发症：1)急性心脏排斥反应(ACR)，第一个死亡的主要原因 移植后一年；和2)心脏移植物血管病(CAV)，这是5年死亡率的最大风险因素 在TX之后的第一年之后。我们的心脏MRI研究已经在HTX中发现了新的成像生物标志物。我们 是第一个在心脏MRI异常测量和潜在的同种异体移植之间建立生理学联系的人 失败：心肌T2和细胞外体积分数(ECV)作为ACR的非侵入性组织生物标志物。我们 证明心肌瘢痕形成、T2和ECV的自然病史可以预测不良临床事件。 HTX收件人。此外，我们的研究表明，捐赠者和接受者不匹配(年龄、性别、体重等)。曾经是 与心脏MRI得出的心肌水肿/炎症、纤维化和 收缩和舒张期功能障碍。在过去的五年里，私人投资机构建立了一个独特的研究数据库 拥有超过&gt；450个全面的心脏MRI检查，包括&gt；110,000个带注释的心脏MRI图像。 对于这项续期申请，我们确定有必要进行进一步的长期跟踪研究，以适应 延缓HTX的疾病进展以确定多参数MRI测量和预测指标随时间的变化 HTX的结果。其次，有关儿童HTX人群中移植物组织和功能的数据很少，而且 需要改进这一弱势群体中捐赠者和受赠者匹配的战略，以使最大限度地 有效利用儿童有限的供体心脏。因此，心脏MRI需要更好地解释 年龄和性别相关的患者习性和生理上的差异，对于HTX的广泛年龄范围至关重要 从儿童到成人。这项研究的更新应用旨在1)开发多参数心脏MRI，用于 评估从儿童到成人的移植物组织(T2，T1，ECV)和功能障碍(心肌速度，应变)， 2)利用现有的大型心脏核磁共振数据库(110,000个标记的心脏核磁共振图像)建立深度 用于心脏MRI自动分析的基于学习的分析流水线，提高效率并减少 评价者之间的可变性，3)确定不良结果的预测因素并评估捐赠者-接受者之间的影响 在一项针对儿童HTX患者的前瞻性研究中，移植物组织、功能和血流的不匹配，以及4)确定 通过利用我们的HTX数据库(&gt；145)预测HTX患者的长期(&gt；5年)预后的心脏指标 HTX接受者在最初的供资周期中获得了现有的基线心脏磁共振成像)。随访心脏 MRI将为移植物组织随时间的变化提供独特的见解，并作为潜在的机制 HTX患者的不同轨迹(无进展与晚发、缓慢进展与快速进展)。

SUMMARY / ABSTRACT Heart transplant (HTx) is a well-established life-saving procedure but is associated with severe complications. Current clinical monitoring algorithms rely on frequent invasive procedures including endomyocardial biopsies and catheter angiography. To address these limitations, the PIs have developed non-invasive comprehensive cardiac MRI, which can quantify regional changes in myocardial tissue and function. Our efforts have focused on the 2 major complications of HTx: 1) acute cardiac rejection (ACR), the leading cause of death in the first year after transplant; and 2) cardiac allograft vasculopathy (CAV), the greatest risk factor for 5-year mortality beyond the first post-Tx year. Our cardiac MRI studies have identified new imaging biomarkers in HTx. We were the first to establish a physiologic link between abnormal cardiac MRI measures and potential allograft failure: myocardial T2 and extracellular volume fraction (ECV) as non-invasive tissue biomarkers for ACR. We demonstrated that the natural history of myocardial scarring, T2, and ECV predicts adverse clinical events in HTx recipients. In addition, our studies showed that donor and recipient mismatch (age, sex, weight, etc.) was significantly associated with cardiac MRI-derived measures of myocardial edema/inflammation, fibrosis, and systolic and diastolic dysfunction. Over the past five years, the PIs have assembled a unique study database with over >450 comprehensive cardiac MRI exams comprising >110,000 annotated cardiac MRI images. For this renewal application, we identified the need to conduct further long-term follow-up studies tailored to the slow disease progression in HTx to identify changes over time in multiparametric MRI measures and predictors of HTx outcome. Second, data on graft tissue and function in the pediatric HTx population are scarce and improved strategies for donor-recipient matching in this vulnerable population are needed to make most efficient use of the limited availability of donor hearts in children. Thus, cardiac MRI needs to better account for age and sex related differences in patient habitus and physiology, critical for the wide age range in HTx from pediatric to adult. The renewal application for this study aims to 1) develop multiparametric cardiac MRI for the assessment of graft tissue (T2, T1, ECV), and dysfunction (myocardial velocities, strain) from pediatric to adult, 2) leverage the existing large cardiac MRI database (110,000 labeled cardiac MRI images) to establish deep learning based analysis pipelines for automated cardiac MRI analysis with improved efficiency and reduced inter-rater variability, 3) to identify predictors of adverse outcomes and to evaluate the impact of donor-recipient mismatch on graft tissue, function, and flow in a prospective study with pediatric HTx patients, and 4) to identify cardiac metrics predictive of long-term (> 5 years) HTx patient outcome by leveraging our HTx database (>145 HTx recipients with existing baseline cardiac MRI acquired during the initial funding cycle). Follow-up cardiac MRI will provide unique insights in changes over time in graft tissue and function as mechanism underlying different HTx patient trajectories (non-progression vs. late onset vs. slow progression vs. fast progression).