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，具有精致的软组织细节，可用于 评估心脏结构和功能，并提供出色的筛查工具，但不能总是避免 更具侵入性的手术，例如心内膜心肌活检（EMB）。介入性 CMR (iCMR) 是一种最低限度的 无辐射的侵入性技术，由于缺乏可用于治疗的有色金属设备而受到阻碍 轻松可视化，从而安全地导航 EMB 等任务。目前，九分之一的死亡人数 美国因心力衰竭 (HF) 造成的医疗费用在 2013 年超过 300 亿美元。其中约 510 万美元 患有心力衰竭的美国人，最终的治疗方法是心脏移植 (HTx)，其中排斥反应通过以下方法进行评估： 心内膜心肌活检 (EMB) – 在 X 射线引导下进行的程序，以获取心内膜心肌活检的随机样本 右心室间隔。然而，许多患者，尤其是患有心肌病的儿童以及接受 HTx 和 由非缺血性心肌病 (NICM) 引起的心力衰竭，心肌不会发生整体变化，但 相反，斑片状疾病通常仅限于左心室的有限部分。因此，EMB 可能会产生 <20% 的病例得到明确诊断。 EMB 的并发症包括心室穿刺、心包穿刺 心包填塞、中风和死亡，EMB 的风险效益比限制了它的使用。但准确诊断 心肌病或心脏排斥的早期识别可以导致明确的治疗或措施来避免 心脏排斥反应分别对个体患者产生巨大影响。因此，我们建议开发一个 与 MRI 兼容的介入设备套件，可直接针对病变心肌（基于 CMR）用于 EMB 和心肌病的治疗，适用于右侧和左侧导管插入术。为此， 我们将开发一种带导丝的有源猪尾导管，用于 iCMR 心导管插入术 与主动 MR 可操纵护套/活组织检查装置或经心肌注射导管组合。这些 设备将能够直接针对疾病，以提高诊断率并减少并发症。 目前，还没有市售的主动 MR 可见 EMB、尾纤或注射导管。重要的 我们在实现临床相关 MR-EMB 设备方面取得的进步包括创建尖颌 EMB 该机制不受加热影响，但在设备打开与关闭时提供特定的 MR 签名， 以及可以确定心肌并置的注射装置，以便治疗达到预期目标 心肌的。此外，由于儿童 HTx 患者在第一年接受多达 6 次 EMB，因此 iCMR 这套设备将显着减少特别脆弱人群的电离辐射。我们的研究 该提案将在自发 NICM 的犬类模型中开发这些设备，该模型的大小与儿童的模型相似 心脏，以确保这些与儿科干预措施兼容。我们在 MRI 领域拥有丰富的专业知识 介入设备和 CMR 将用于实现这一目标。因此，我们的目标是开发这些 MR 引导设备将 iCMR 的覆盖范围扩大到儿童和成人。