Comprehensive Cardiac Structure-Function Analysis in Heart Transplantation

心脏移植中全面的心脏结构功能分析

• 批准号: 10208494
• 负责人: James Carr
• 金额: $ 69.53万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-04 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10208494
• 关键词: Acute; Address; Adult; Age; Algorithms; Allografting; Angiography; Biopsy; Body mass index; Cardiac; Catheters; Cause of Death; Cessation of life; Characteristics; Child; Childhood; Cicatrix; Clinical; Data; Databases; Diagnostic; Diffuse; Disease Progression; Donor Selection; Donor person; Early Diagnosis; Edema; Event; Failure; Fibrosis; Follow-Up Studies; Functional disorder; Funding; Gender; Goals; Heart; Heart Abnormalities; Heart Rate; Heart Transplantation; Heart failure; Height; Hospitalization; Hypertension; Image; Inflammation; Label; Left; Life; Link; Longterm Follow-up; Magnetic Resonance Imaging; Measures; Methodology; Modeling; Monitor; Motion; Myocardial; Myocardial tissue; Natural History; Nature; Outcome; Outcome Study; Patient-Focused Outcomes; Patients; Pattern; Performance; Phase; Physiological; Physiology; Population; Prevalence; Procedures; Prospective Studies; Protocols documentation; Resolution; Right Ventricular Dysfunction; Risk Factors; Role; Sampling Errors; Savings; Severities; Sex Differences; Smoking; Structure; Testing; Time; Tissue Grafts; Tissues; Training; Transplant Recipients; Transplantation; Transplantation Surgery; Transplanted Heart Complication; Vascular Diseases; Ventricular; Vulnerable Populations; Weight; adverse outcome; analysis pipeline; automated analysis; base; cohort; cost estimate; deep learning; extracellular; flexibility; follow-up; graft failure; health care service utilization; heart allograft; heart dimension/size; heart function; imaging biomarker; improved; improved outcome; insight; interstitial; mortality; non-invasive imaging; novel; outcome prediction; pediatric patients; sex; spatiotemporal; standard of care; tissue biomarkers; transplant database; treatment choice

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).

摘要 /摘要 心脏移植（HTX）是一种良好的挽救生命的程序，但与严重的并发症有关。 当前的临床监测算法依赖于频繁的侵入性手术，包括内膜活检 和导管血管造影。为了解决这些限制，PI已开发出非侵入性综合性 心脏MRI，可以量化心肌组织和功能的区域变化。我们的努力集中在 关于HTX的2个主要并发症：1）急性心脏排斥（ACR），第一次死亡的主要原因 移植后一年； 2）心脏同种异体血管病（CAV），这是5年死亡率的最大风险因素 超出了第一个tx年。我们的心脏MRI研究已经确定了HTX中的新成像生物标志物。我们 是第一个在异常心脏MRI测量和潜在同种异体移植物之间建立生理联系的人 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 证明心肌疤痕，T2和ECV的自然史预测了不良临床事件 HTX收件人。此外，我们的研究表明，捐助者和接受者不匹配（年龄，性别，体重等）是 与心肌水肿/炎症，纤维化和 收缩和舒张功能障碍。在过去的五年中，PI组装了一个独特的研究数据库 超过450个全面的心脏MRI检查，包括> 110,000个注释的心脏MRI图像。 对于此续签应用，我们确定了需要进行进一步的长期随访研究 HTX的疾病进展缓慢，以确定多参数MRI测量和预测因子的随着时间的变化 HTX结果。其次，有关移植组织和儿科HTX种群中功能的数据很少，并且 需要改善供体接触式匹配的策略，以使大多数人口大多数 有效利用儿童供体心的有限利用率。因此，心脏MRI需要更好地解释 年龄和性别相关的患者习惯和生理学差异，对HTX的广泛年龄范围至关重要 成人小儿。本研究的续签应用旨在1）开发多参数心脏MRI 从小儿到成人的移植组织（T2，T1，ECV）和功能障碍（心肌速度，菌株）评估 2）利用现有的大型心脏MRI数据库（110,000个标记心脏MRI图像）来建立深度 基于学习的分析管道，用于自动心脏MRI分析，并提高效率并降低 评价者间的可变性，3）识别不良结果的预测指标并评估供体 - 招聘的影响 在小儿HTX患者的前瞻性研究中，对移植组织，功能和流动的不匹配，4） 通过利用我们的HTX数据库来预测长期（> 5年）HTX患者结果的心脏指标（> 145 在初始资金周期中获得的现有基线心脏MRI的HTX接收者）。后续心脏 MRI将在移植组织中随时间变化提供独特的见解，并作为基础机制起作用 不同的HTX患者轨迹（非促进与晚期发作与缓慢进展与快速进展）。