Optimized CMR imaging of chemotherapy cardiotoxicity

描述（由申请人提供）：本R21/R33申请响应NCI项目公告PA-04-095，题为“体内成像的新技术”，旨在开发和提供用于癌症患者的创新、高风险/高增益图像采集和增强方法。我们的拨款旨在实现开发心血管磁共振（CMR）成像方法的特定目标，用于早期检测阿霉素诱导的心脏毒性。虽然阿霉素延长了许多患有癌症的儿童和成人的生存期并减轻了肿瘤负担；它的使用会导致不可逆的充血性心力衰竭（CHF）和死亡。检测阿霉素心脏毒性最准确的方法是心肌内活检，但这种方法是侵入性的，相对昂贵，不适合重复检查。更常见的是，在阿霉素治疗过程中，连续放射性核素心室图用于评估左心室射血分数（LVEF）。LVEF下降表明心脏毒性风险增加，当这种情况发生时，通常的做法是停止治疗。然而，重要的是，LVEF的下降可能只发生在持续的不可逆心脏损伤之后。因此，在癌症患者中，阿霉素的总剂量通常是有限的。在LVEF下降之前，一种安全、广泛可用、无创的检测阿霉素诱导的心脏毒性的方法在两个方面是有用的。首先，早期发现心脏毒性有助于预防CHF的发展，其次，没有心脏毒性将允许继续治疗，使患者能够充分认识到药物的益处。虽然没有被要求，但我们提供的试验数据表明，CMR图像可以在心脏维持LVEF下降之前识别早期心肌损伤。在R21阶段，我们描述了开发和进一步测试CMR方法所需的软件、统计分析和招聘策略。在该奖项为期3年的R33阶段，我们提供研究设计来评估这种新开发的CMR方法的临床应用。我们在R21和R33应用程序之间的里程碑文档中定义了性能目标，以确定从R21过渡到R33阶段的适用性。每个阶段（R21和R33）包含单独的A-D部分，根据说明书的指示，我们指定（但不重复或重新键入）R21阶段的A至D部分中适用于R33阶段的组件。

DESCRIPTION (provided by applicant): This R21/R33 application responds to NCI program announcement PA-04-095 entitled, "Novel Technologies for In Vivo Imaging" directed toward the development and delivery of innovative, high-risk/high-gain image acquisition and enhancement methods for use in cancer patients. Our grant is designed to achieve specific aims for developing a cardiovascular magnetic resonance (CMR) imaging method for early detection of doxorubicin induced cardiotoxicity. Although doxorubicin prolongs survival and reduces tumor burden for many children and adults with cancer; its use can cause irreversible congestive heart failure (CHF) and death. The most accurate method for detecting doxorubicin cardiotoxicity is an intramyocardial biopsy, but this procedure is invasive, relatively expensive, and not well suited for repetitive examinations. More commonly, serial radionuclide ventriculograms are used to assess left ventricular ejection fraction (LVEF) during the course of doxorubicin therapy. A fall in LVEF indicates those at increased risk for cardiotoxicity, and it is common practice to stop therapy when this occurs. Importantly however, a fall in LVEF may occur only after irreversible cardiac damage has been sustained. For this reason, the total dose of doxorubicin is often limited in cancer patients. A safe, widely available, noninvasive method to detect doxorubicin induced cardiotoxicity before a fall in LVEF occurs would be useful in 2 respects. First, early detection of cardiotoxicity could help prevent the development of CHF, and second, the absence of cardiotoxicity would allow the continuation of therapy so that patients could realize the full benefit of the medication. Although not requested, we provide pilot data indicating that CMR images identify early myocardial injury before the heart sustains a drop in LVEF. In the R21 phase of the award, we describe the software, statistical analyses, and recruitment strategy needed to develop and further test our CMR methodology. In the 3-year R33 phase of the award, we provide the study design to assess the clinical utility of this newly developed CMR methodology. We define the performance targets for determining suitability for transition from the R21 to the R33 phase in a Milestones document that resides between the R21 and R33 application. Each phase (R21 & R33) contains separate sections A-D, and as directed by the instructions, we designate (but do not repeat or re-type) the components of sections A through D of the R21 phase that are applicable to the R33 phase.