Acute-infarct selective cardiac MRI contrast agent

急性梗塞选择性心脏MRI造影剂

• 批准号: 7110833
• 负责人: Balazs Ruzsics
• 金额: $ 14万
• 依托单位: ELGAVISH PARAMAGNETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-28 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110833
• 关键词: bioimaging /biomedical imaging; cardiovascular imaging /visualization; catheterization; contrast media; diagnosis design /evaluation; disease /disorder model; dogs; gadolinium; image enhancement; magnetic resonance imaging; myocardial infarct sizing; myocardial infarction; radiodiagnosis; radiography

DESCRIPTION (provided by applicant): Reliable diagnostic differentiation between acute and chronic myocardial infarcts would be of great benefit for cardiac surgeons and interventional cardiologists. Such differentiation could be used to make decisions about which vessels and in what order would be reopened or bypassed. MRI is an intrinsically noninvasive diagnostic tool and the Delayed Enhancement MRI technique is capable of highlighting infarct by the accumulation of contrast agents (e.g., MagnevistZ) into it, causing MRI intensity hyperenhancement in infarcted myocardial tissue. Unfortunately, however, the technique, with the presently available contrast agents, does not differentiate between acute, i.e., relatively fresh, infarcts and chronic, i.e., old infarcts. A recently proffered addition to this technique, the use of T2-weighted images taken before the administration of the contrast agent, does sometimes distinguish acute infarcts from chronic infarcts but due to various factors it does not do so in a predictable manner. This unpredictability essentially prevents the use of this technique in clinical decision making. Based on our preliminary data, we offer the use of a new myocardial contrast agent, Gadolinium-ABE-DTTA, which selectively highlights acute infarcts by causing signal hyperenhancement, yet does not cause hyperenhancement in infarcts that are beyond 2 weeks old. MRI imaging, using this agent, would allow the sought-after differentiation of acute from chronic infarct in a highly reliable manner. Our long term objective, using a canine model of myocardial infarction, is to prove the practical ability to exercise "vessel triage", to characterize the parameters for its application, and to investigate the tissue mechanism of the differentiation. Among the parameters the optimal dose, the earliest post-infarct time of the emergence of signal hyperenhancement, and the time window (earliest and latest time) of the effect will be determined. As a first step, in this Phase I project a limited objective will be achieved, to prove with sufficient statistical significance the ability of this agent to show differentiation between early acute (less than 2 days old) and late acute (more than 8 days old) infarcts. A Phase II application will be submitted once this limited objective is met. Following Phase II, which will pursue the long term objective described above, steps will be taken towards commercialization.

描述（由申请人提供）：急性和慢性心肌梗死之间的可靠诊断区分将对心脏外科医生和介入心脏病学家非常有益。这种区分可用于决定哪些血管以及以何种顺序重新开放或绕过。MRI是一种本质上非侵入性的诊断工具，并且延迟增强MRI技术能够通过造影剂（例如，结果显示，在梗塞心肌组织中，磁共振成像（MRI）强度增强。然而，不幸的是，使用目前可用的造影剂，该技术不能区分急性，即，相对新鲜的梗塞和慢性的，即，陈旧性梗死最近提出的一种对该技术的补充，即使用造影剂给药前拍摄的T2加权图像，有时确实能区分急性梗死和慢性梗死，但由于各种因素，它不能以可预测的方式做到这一点。这种不可预测性基本上阻止了这种技术在临床决策中的使用。根据我们的初步数据，我们提供了一种新的心肌造影剂，钆-ABE-DTTA，它选择性地突出急性梗死引起的信号增强，但不会引起超增强梗死超过2周。MRI成像，使用这种药物，将允许寻求区分急性和慢性梗死在一个高度可靠的方式。我们的长期目标，使用犬心肌梗死模型，是要证明的实际能力，行使“血管分类”，其应用的参数，并探讨分化的组织机制。在这些参数中，将确定最佳剂量、出现信号增强的最早梗死后时间以及效果的时间窗（最早和最晚时间）。作为第一步，在该I期项目中，将实现有限的目标，以充分的统计学显著性证明该药剂显示早期急性（小于2天）和晚期急性（大于8天）梗死之间的区分的能力。一旦达到这一有限的目标，将提交第二阶段申请。第二阶段将追求上述长期目标，之后将采取步骤实现商业化。

项目成果

Differentiation of acute and four-week old myocardial infarct with Gd(ABE-DTTA)-enhanced CMR.

• DOI: 10.1186/1532-429x-12-22
• 发表时间: 2010-04-07
• 期刊: Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
• 作者: Kirschner R;Toth L;Varga-Szemes A;Simor T;Suranyi P;Kiss P;Ruzsics B;Toth A;Baker R;Brott BC;Litovsky S;Elgavish A;Elgavish GA
• 通讯作者: Elgavish GA

Acute infarct selective MRI contrast agent.

• DOI: 10.1007/s10554-011-9811-8
• 发表时间: 2012-02
• 期刊: INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
• 影响因子: 2.1
• 作者: Robert Kirschner;Akos Varga-Szemes;Tamas Simor;Suranyi, Pal;Kiss, Pal;Ruzsics, Balazs;Brott, Brigitta C.;Elgavish, Ada;Elgavish, Gabriel A.
• 通讯作者: Elgavish, Gabriel A.