MR-compatible Devices for the Diagnosis and Treatment of Cardiomyopathies

用于诊断和治疗心肌病的 MR 兼容设备

• 批准号: 10198263
• 负责人: DARA L KRAITCHMAN
• 金额: $ 79.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-20 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10198263
• 关键词: 3-Dimensional; 7 year old; Adult; Adverse event; Affect; Age; American; Angiography; Animal Model; Animals; Biopsy; Blood; Canis familiaris; Cardiac; Cardiac Catheterization Procedures; Cardiomyopathies; Cardiovascular Diseases; Cardiovascular system; Catheterization; Catheters; Cessation of life; Child; Childhood; Client; Clinical; Clinical Trials; Complication; Consensus; Data; Device or Instrument Development; Devices; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Dilated Cardiomyopathy; Disease; Echocardiography; Electrocardiogram; Ensure; Epicardium; Etiology; Exposure to; Fluoroscopy; Genetic; Global Change; Goals; Graft Rejection; Health Care Costs; Heart; Heart Diseases; Heart Transplantation; Heart failure; Heating; Histopathology; Human; Imaging Techniques; Immunologics; Incidence; Infection; Inflammation; Injections; Injury; Intervention; Ionizing radiation; Jaw; Lead; Left; Left ventricular structure; Life; Longevity; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Medical; Modeling; Monitor; Myocardial; Myocardial Infarction; Myocarditis; Myocardium; Organ; Patients; Pediatric Cardiomyopathy; Pericardial body location; Prevalence; Primary idiopathic dilated cardiomyopathy; Procedures; Prognosis; Puncture procedure; Radiation; Recommendation; Research Proposals; Roentgen Rays; Route; Safety; Sampling; Screening procedure; Secondary to; Serious Adverse Event; Side; Solid; Specimen; Stroke; Structure; Suggestion; Techniques; Testing; Therapeutic; Time; Tissues; Translations; Transplant Recipients; Ventricular; Ventricular Arrhythmia; Ventricular Dysfunction; Ventricular septum; Visualization; Vulnerable Populations; Waiting Lists; Work; accurate diagnosis; base; cardiac device; cardiogenesis; chemotherapy; clinically relevant; congenital heart disorder; detection method; diagnostic accuracy; disease diagnosis; hemodynamics; image guided; improved; in vitro testing; in vivo; individual patient; minimally invasive; mortality; mortality risk; myocardial injury; non-invasive imaging; pediatric patients; pre-clinical; prevent; risk benefit ratio; soft tissue; translation to humans

Cardiac magnetic resonance (CMR) is a non-invasive imaging technique with exquisite soft-tissue detail for the assessment of heart structure and function and provides an excellent screening tool but cannot always obviate more invasive procedures, such as endomyocardial biopsy (EMB). Interventional CMR (iCMR) is a minimally invasive technique without radiation, which has been hampered by the lack of non-ferrous devices that can be easily visualized, enabling the navigation of tasks, such as EMB, safely. Currently, one in nine deaths in the US is attributed to heart failure (HF), with health care costs exceeding $30 billion in 2013. Of the ~5.1 million Americans with HF, the definitive treatment is heart transplantation (HTx), where rejection is assessed with endomyocardial biopsy (EMB) – a procedure performed under X-ray guidance to obtain random samples of the right ventricular septum. However, many patients, especially children with cardiomyopathy and after HTx and HF caused by non-ischemic cardiomyopathies (NICM), do not have global changes to the myocardium, but rather, patchy disease, which is often restricted to limited portions of the left ventricle. Thus, EMB may yield a definitive diagnosis in <20% of the cases. As complications of EMB include ventricular puncture, pericardial tamponade, stroke, and death, the risk-benefit ratio of EMB limits its use. However, accurate diagnosis of cardiomyopathies or early recognition of heart rejection can lead to definitive treatment or measures to avoid heart rejection, respectively, with enormous individual patient impact. Therefore, we propose to develop an MRI-compatible suite of interventional devices to allow direct targeting of diseased myocardium (based on CMR) for EMB and treatment of cardiomyopathies, for both right- and left-sided catheterization. To this end, we will develop an active pigtail catheter with a guidewire for iCMR cardiac catheterization to be used in combination with an active MR-steerable sheath/bioptome device or transmyocardial injection catheter. These devices will enable direct targeting of the disease to increase diagnostic yield and decrease complications. Currently, there are no commercially available active MR-visible EMB, pigtail, or injection catheters. Significant advances to our realization of a clinically relevant MR-EMB device include the creation of a sharp-jaw EMB mechanism that is safe from heating, but provides a specific MR signature when the device is open vs. closed, and injection devices that can determine myocardial apposition so that therapeutics reach the intended target of the myocardium. Furthermore, as pediatric HTx patients receive up to six EMBs in the first year, the iCMR suite of devices will significantly reduce ionizing radiation in a particularly vulnerable population. Our research proposal will develop these devices in a canine model of spontaneous NICM that is similar in size to children's hearts to ensure these are compatible with pediatric interventions. Our extensive expertise in MRI interventional devices and CMR will be used to achieve this objective. Thus, our goal will be to develop these MR-guided devices to expand the reach of iCMR to children and adults.

心脏磁共振（CMR）是一种非侵入性成像技术，具有精致的软组织细节， 心脏结构和功能的评估，并提供了一个很好的筛选工具，但不能总是 更具侵入性的手术，如肌内膜活检（EMB）。介入性CMR（iCMR）是最低限度的 没有辐射的侵入性技术，这一直受到缺乏有色金属设备的阻碍， 易于可视化，从而能够安全地导航任务（如EMB）。目前，每九个死亡中就有一个 在美国，心力衰竭（HF）是一种常见的疾病，2013年的医疗保健费用超过300亿美元。在510万人中， 在患有HF的美国人中，确定性治疗是心脏移植（HTx），其中用 肌内膜活检（EMB）-在X射线引导下进行的程序，以获得随机样本的 右室间隔然而，许多患者，特别是心肌病儿童和HTx后， 由非缺血性心肌病（NICM）引起的HF对心肌没有整体变化，但 而是斑片状疾病，通常局限于左心室的有限部分。因此，EMB可以产生 确诊率<20%。由于EMB的并发症包括脑室穿刺、心包 心包填塞，中风和死亡，EMB的风险效益比限制了它的使用。然而，准确诊断 心肌病或心脏排斥反应的早期识别可以导致明确的治疗或措施，以避免 心脏排异反应，对个体患者的影响巨大。因此，我们建议发展一个 MRI兼容的介入器械套件，允许直接靶向病变心肌（基于 CMR）用于EMB和心肌病治疗，用于右侧和左侧导管插入术。为此目的， 我们将开发一种用于iCMR心脏导管插入术的带导丝的主动猪尾导管， 与主动MR可操纵鞘管/活检钳装置或经心肌注射导管组合。这些 这些设备将能够直接瞄准疾病，以提高诊断率并减少并发症。 目前，没有市售的有源MR可见EMB、猪尾或注射导管。显著 我们实现临床相关MR-EMB设备的进展包括创建尖颌EMB 不会发热的机制，但在器械打开与关闭时提供特定的MR特征， 以及可以确定心肌并置从而使治疗剂到达预定目标的注射装置 心肌层此外，由于儿童HTx患者在第一年接受多达6次EMB，iCMR 这套装置将大大减少特别脆弱人群中的电离辐射。我们的研究 一项提案将在犬自发NICM模型中开发这些设备，其大小与儿童相似 确保这些心脏与儿科干预措施兼容。我们在MRI领域的广泛专业知识 介入器械和CMR将用于实现这一目标。因此，我们的目标将是开发这些 MR引导设备，将iCMR的覆盖范围扩大到儿童和成人。