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: 10471268
• 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/10471268
• 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; Interventional Imaging; 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; canine model; cardiac device; cardiogenesis; 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; 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，具有精细的软组织细节，可用于 评估心脏结构和功能，提供了一种极好的筛查工具，但并不总是可以取代 更具侵入性的程序，如心内膜心肌活检(EMB)。介入CMR(ICMR)是一种最低限度的 没有辐射的侵入性技术，由于缺乏可以 易于可视化，支持安全地导航EMB等任务。目前，世界上每九个死亡病例中就有一个 美国被归因于心力衰竭(HF)，2013年医疗保健成本超过300亿美元。在510万人中 美国人患有心力衰竭，最终的治疗方法是心脏移植(HTX)，排斥反应的评估是通过 心内膜心肌活检(EMB)-在X射线引导下进行的一种程序，以获取随机样本 右室间隔。然而，许多患者，特别是患有心肌病的儿童，在HTX和 由非缺血性心肌病(NICM)引起的心衰，对心肌没有全局性变化，但 更确切地说，是斑片状疾病，这种疾病通常局限于左心室的有限部分。因此，教统局可能会产生一个 明确诊断的病例占20%。由于EMB的并发症包括脑室穿孔、心包 EMB的风险-收益比限制了其使用，如填塞、中风和死亡。然而，准确的诊断 心肌病或心脏排斥反应的早期识别可导致明确的治疗或避免 心脏排斥反应分别对个体患者产生巨大影响。因此，我们建议开发一种 与MRI兼容的介入设备套件，允许直接靶向病变心肌(基于 CMR)，用于EMB和治疗心肌病，用于右侧和左侧导管术。为此， 我们将开发一种带导丝的活性猪尾导管，用于ICMR心导管插入术 与主动MR可引导鞘/活组织刀装置或经心肌注射导管相结合。这些 这些设备将能够直接瞄准疾病，以提高诊断效率并减少并发症。 目前，还没有商业上可用的有源磁共振可见的EMB、辫子或注射导管。意义重大 我们实现临床上相关的MR-EMB设备的进展包括创造一种锋利的颌部EMB 一种防加热安全的机构，但在设备打开与关闭时提供特定的MR签名， 和注射装置，可以确定心肌定位，使治疗达到预期的目标 对心肌的影响。此外，由于儿童HTX患者在第一年接受了最多6个eMBS，ICMR 一套设备将显著减少特别脆弱人群的电离辐射。我们的研究 一项提案将在自发性NICM的犬模型中开发这些装置，这种模型的大小与儿童的相似 心脏，以确保这些与儿科干预相兼容。我们在核磁共振方面的广泛专业知识 将使用介入设备和CMR来实现这一目标。因此，我们的目标将是开发这些 MR引导的设备，将ICMR的覆盖范围扩大到儿童和成人。