Low-dose SPECT/CT for imaging chemotherapy-induced microvascular cardiotoxicity

低剂量 SPECT/CT 对化疗引起的微血管心脏毒性进行成像

• 批准号: 9049541
• 负责人: Chi Liu
• 金额: $ 76.27万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9049541
• 关键词: Animal Model; Animals; Biopsy; Blood; Blood Circulation; Blood Vessels; Blood Volume; Cancer Patient; Cancer Survivor; Canis familiaris; Cardiac; Cardiotoxicity; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; Clinical assessments; Coupling; Data; Detection; Dose; Doxorubicin; Drops; EFRAC; Early Diagnosis; Erythrocytes; Functional disorder; Future; Goals; Guidelines; Health; Heart; Human; Hybrids; Image; Imaging Techniques; Injection of therapeutic agent; Injury; Iodine; Kidney; Label; Left Ventricular Ejection Fraction; Measurement; Measures; Mechanics; Mediating; Methods; Microcirculation; Microscopic; Motion; Myocardial; Myocardium; Neuregulins; Pathway interactions; Patients; Perfusion; Play; Process; Protocols documentation; Radiation; Radiolabeled; Recruitment Activity; Reproducibility; Resolution; Rest; Role; Sample Size; Scanning; Screening for cancer; Signal Pathway; Slice; Speed; Stress; Testing; Thick; Time; Toxic effect; Tracer; Translating; Trastuzumab; Variant; Ventricular; X-Ray Computed Tomography; aging population; angiogenesis; animal imaging; base; cancer therapy; cellular imaging; chemotherapeutic agent; chemotherapy; clinical practice; clinically relevant; data acquisition; design; heart motion; imaging modality; improved; in vivo; indexing; low-dose spiral CT; non-invasive imaging; novel; novel therapeutics; outcome forecast; radiotracer; reconstruction; respiratory; single photon emission computed tomography

DESCRIPTION (provided by applicant): Cancer chemotherapy often induces cardiotoxicity, which can have a significant impact on the overall prognosis and survival of cancer patients. Current guidelines to screen for cancer therapy-related cardiotoxicity are primarily based on serial assessment of left ventricular ejection fraction (EF), which is not a sensitive index of cardiotoxicity and may only decline at a time point that is too late to reerse the process. In addition to cardiac function, the microvasculature plays a critical rol in cardiotoxicity. There is a close bidirectional coupling of regional myocardial mechanics and microvascular perfusion. Many of the newer chemotherapy agents can directly cause microvascular injury, which may precede any EF drop. Due to an increasing aging population and rapid introduction of new therapy agents, more patients and cancer survivors are expected to suffer from cardiotoxicity. Therefore, there is an urgent need to develop novel non-invasive imaging techniques that might allow early detection of microvascular injury of patients with cardiotoxicity prior to a drop in EF. With this urgent clinical need, we propose to quantify Intramyocardial blood volume (IMBV) as a novel measurement of microcirculation function. 99mTc-labeled red blood cell (RBC) is a clinically available blood pool tracer for EF measurement and RBC imaging using Single Photon Emission Computed Tomography (SPECT) is a natural approach to estimate IMBV as the tracer stays in the intravascular circulation. However, accurate quantification of IMBV using SPECT is challenging, because 99mTc-RBC has ~5-6 fold higher activity in the blood pool than in myocardium, the spill-over counts from blood pool to the myocardium mainly due to poor resolution and respiratory/cardiac motion can cause substantial IMBV overestimation. We have developed various novel quantitative low-dose SPECT/CT methods including CT-based partial volume correction and motion corrections, and have demonstrated the feasibility of quantifying IMBV using SPECT/CT in large animal studies. We hypothesize that accurate measurement of IMBV can provide an early index of disruption of the microcirculation and vascular reserve and improve detection of cancer therapy induced cardiotoxicity. In this proposal, we will optimize, validate, and translate this low-dose (<2 mSv) quantitative SPECT/CT imaging approach into large animal and human studies. We will pursue the study through four Specific Aims. In Aim 1, we will optimize the low-dose SPECT/CT imaging approaches. In Aim 2, we will optimize the low-dose contrast CT data acquisition protocols. In Aim 3, we will quantify and validate the serial changes of IMBV in an established large animal model. In Aim 4, we will establish the feasibility of this SPECT/CT imaging approach in patient studies. This project is a stepping-stone to translate this imaging method to large clinical trials and clinical practice.

描述（由申请人提供）：癌症化疗通常会引起心脏毒性，这会对癌症患者的整体预后和生存产生重大影响。目前筛查癌症治疗相关心脏毒性的指南主要基于左心室射血分数（EF）的连续评估，这不是心脏毒性的敏感指标，并且可能只会在来不及逆转该过程的时间点下降。 除了心脏功能外，微脉管系统在心脏毒性中也发挥着关键作用。 局部心肌力学存在紧密的双向耦合 和微血管灌注。 许多较新的化疗药物可直接导致微血管损伤，这可能会先于 EF 下降。由于人口老龄化的加剧和新治疗药物的快速推出，预计会有更多的患者和癌症幸存者遭受心脏毒性。因此，迫切需要开发新型非侵入性成像技术，以便在 EF 下降之前及早发现心脏毒性患者的微血管损伤。鉴于这种紧迫的临床需求，我们建议量化心肌内血容量（IMBV）作为微循环功能的一种新测量方法。 99mTc 标记的红细胞 (RBC) 是一种临床可用的血池示踪剂，用于 EF 测量，并且使用单光子发射计算机断层扫描 (SPECT) 进行 RBC 成像是估计 IMBV 的自然方法，因为示踪剂停留在血管内循环中。然而，使用 SPECT 准确定量 IMBV 具有挑战性，因为 99mTc-RBC 在血池中的活性比心肌中高约 5-6 倍，从血池到心肌的溢出计数主要是由于分辨率差和呼吸/心脏运动可能导致 IMBV 严重高估。 我们开发了各种新型定量低剂量 SPECT/CT 方法，包括基于 CT 的部分体积校正和运动校正，并证明了在大型动物研究中使用 SPECT/CT 量化 IMBV 的可行性。 我们假设准确测量 IMBV 可以提供微循环和血管储备破坏的早期指标，并改善癌症治疗引起的心脏毒性的检测。 在 根据该提案，我们将优化、验证这种低剂量（<2 mSv）定量 SPECT/CT 成像方法并将其转化为大型动物和人体研究。我们将通过四个具体目标来开展这项研究。在目标 1 中，我们将优化低剂量 SPECT/CT 成像方法。在目标 2 中，我们将优化低剂量对比 CT 数据采集协议。 在目标 3 中，我们将量化并验证 IMBV 在 建立大型动物模型。在目标 4 中，我们将确定这种 SPECT/CT 成像方法在患者研究中的可行性。该项目是将这种成像方法转化为大型临床试验和临床实践的垫脚石。