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: 10671041
• 负责人: DARA L KRAITCHMAN
• 金额: $ 76.63万
• 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/10671041
• 关键词: 3-Dimensional; 7 year old; Adult; Adverse event; Affect; Age; American; Angiography; Animal Model; Animals; Biopsy; Blood; Breeding; 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; Development; 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; 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; 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; Techniques; Testing; Therapeutic; Tissues; Translations; Transplant Recipients; Venous; Ventricular; Ventricular Arrhythmia; Ventricular Dysfunction; Ventricular septum; Visualization; Vulnerable Populations; Waiting Lists; Work; accurate diagnosis; canine model; cardiac device; chemotherapy; clinically relevant; congenital heart disorder; detection method; diagnostic accuracy; disease diagnosis; hemodynamics; image guided; imaging facilities; improved; in vitro testing; in vivo; individual patient; minimally invasive; mortality; myocardial injury; non-invasive imaging; pediatric patients; pre-clinical; prevent; risk/benefit ratio; soft tissue; translation to humans; translational model

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，具有独特的软组织细节 评估心脏结构和功能，并提供出色的筛查工具，但不能总是消除 更多的侵入性程序，例如内膜活检（EMB）。介入的CMR（ICMR）是最小的 没有辐射的侵入性技术，由于缺乏有色人种的设备而受到阻碍 易于可视化，可以安全地进行任务的导航，例如EMB。目前，有九人死亡 美国归因于心力衰竭（HF），2013年的医疗保健费用超过300亿美元。 患有HF的美国人，确定的治疗是心脏移植（HTX），在其中评估拒绝 心内膜活检（EMB） - 根据X射线指导进行的一种程序，以获取随机样本 右心室隔膜。但是，许多患者，尤其是心肌病的儿童以及HTX之后 由非缺血性心肌病（NICM）引起的HF，对心肌没有全球变化，而是 相反，斑点疾病通常仅限于左心室的有限部分。那，EMB可能会产生 <20％的病例中的明确诊断。由于缠结并发症包括心室穿刺，心包 EMB的风险效益比限制了其使用量。但是，准确的诊断 心肌病或早期识别心排斥可以导致明确的治疗或措施以避免 心脏排斥分别具有增强的个体患者影响。因此，我们建议开发 介入的MRI兼容套件允许直接靶向患病的心肌（基于 cmr）用于胚胎病和左侧导管插入术的胚胎和治疗。为此， 我们将开发一个主动辫子导管，并使用用于ICMR心脏导管插入术的导管 与主动的MR驱动鞘/生物代理设备或跨心脏注入导管结合使用。这些 设备将使疾病的直接靶向增加诊断产量并减少并发症。 目前，尚无商业活动的MR可见胚，辫子或注射导管。重要的 我们实现临床相关的MR-EMB设备的进步包括创建尖锐的emb 可以安全加热的机构，但是当设备打开与关闭时，提供了特定的MR签名， 和可以确定心肌置术的注射装置，以便治疗达到预期的靶标 心肌。此外，由于小儿HTX患者在第一年获得多达六个EMB，因此ICMR 设备套件将大大减少特别脆弱的人群的电离辐射。我们的研究 提案将在赞助NICM的犬类模型中开发这些设备，该设备的大小与儿童的大小相似 心脏以确保它们与小儿干预兼容。我们在MRI方面广泛的专业知识 介入设备和CMR将用于实现这一目标。那就是我们的目标是开发这些 MR指导设备将ICMR覆盖到儿童和成人的范围。