NIR Hypoxia Imaging of Breast Tumor Response to Neoadjuvant Chemotherapy in Vivo

描述(由申请人提供)： 近红外(NIR)多光谱成像是表征女性乳房组织成分的独特工具。这种方法的主要优点是它能够提供组织氧饱和度(StO2)以及总血红蛋白浓度(HBT)、水含量(H2O%)和弹性散射参数的图像。由于微循环和氧合在肿瘤进展和消退中起着重要作用，评估它们对新辅助化疗的反应的变化可能揭示治疗反应的早期预后生物标志物，这些生物标志物可以用于改变和/或优化更个性化的患者的治疗过程。用近红外光谱断层扫描评估高氧气体吸入后肿瘤氧合的动态对比增强似乎是可行的，并且可以提供容易获得的、低成本的图像信号来预测乳腺对化疗的治疗反应。这项建议的总体目标是开发和评估动态近红外断层血氧仪，通过评估高氧气体吸入过程中肿瘤氧合的时间变化来表征局部晚期乳腺癌对新辅助化疗的反应。我们假设，在呼吸100%氧气前后有更大和更快变化的肿瘤对新辅助化疗有更好的临床反应。这一假说将通过以下方式进行量化评估：1)发展目前的近红外多光谱断层成像系统，以0.1 Hz的图像帧速率对呼吸100%氧气诱导的肿瘤内的动态氧合变化进行成像；2)对治疗过程中不同时间高氧吸入对肿瘤的氧合反应进行量化；以及3)对反应的病理和临床结果进行量化，以便测试与治疗过程早期记录的血氧变化的相关性。达特茅斯学院通过达特茅斯-希区柯克医学中心的诺里斯棉花癌症中心，有大量的资源可以利用来进行这项拟议的研究。自1999年以来，一个包括诊断放射学、外科肿瘤学、内科肿瘤学、外科病理学和医学工程学的临床专家在内的研究小组被配置为开发和评估用于癌症检测、诊断和治疗监测的乳房成像技术。拟议的项目是该小组研究的重要组成部分。除了主要研究人员蒋树东教授和Peter A.Kaufman博士(医学肿瘤学)外，Keith D.Paulsen教授、Brian W.Pogue教授和Wendy A.Wells博士(病理学系)将作为目前资助的乳房成像研究拨款的补充，成为实现拟议的具体目标的重要合作者。公共卫生相关性：该项目将开发和评估动态近红外(NIR)断层血氧仪，通过评估高氧气体吸入过程中肿瘤氧合的时间变化来表征局部晚期乳腺癌对新辅助化疗的反应。在治疗过程中纵向获得的近红外血氧仪将与病理终点相关，以确定是否可以在动态近红外氧合信号中识别治疗反应的早期预后生物标志物，这些标志物可用于定制未来乳腺癌患者的治疗决策。

DESCRIPTION (provided by applicant): Near-infrared (NIR) multi-spectral imaging is a unique tool for characterizing tissue composition in the female breast. The major advantage of this modality is its ability to provide images of tissue oxygen saturation (StO2) as well as total hemoglobin concentration (HbT), water fraction (H2O%) and elastic scattering parameters. Because microcirculation and oxygenation play such major roles in tumor progression and regression, assessing their variation in response to neoadjuvant chemotherapy may reveal early prognostic biomarkers of treatment response that could be used to alter and/or optimize the course of treatment on a more individualized patient basis. Assessing dynamic contrast enhancement in tumor oxygenation after hyperoxic gas inhalation with NIR spectral tomography appears to be feasible and may provide easily- acquired, low cost image signatures for predicting therapeutic response to chemotherapy in the breast. The overall goal of this proposal is to develop and evaluate dynamic NIR tomographic oximetry for characterizing the response of locally advanced breast cancers to neoadjuvant chemotherapy by assessing the temporal variation in tumor oxygenation during hyperoxic gas inhalation. We hypothesize that tumors with initially larger and faster changes before and after breathing 100% oxygen will have better clinical responses to neoadjuvant chemotherapy. This hypothesis will be quantitatively assessed by 1) advancing the current NIR multi-spectral tomography system to image dynamic oxygenation changes within the tumor, induced by breathing 100% oxygen, with a 0.1 Hz image frame rate, 2) quantifying the tumor oxygenation response with respect to hyperoxic inhalation at different times during the course of therapy, and 3) quantifying the pathological and clinical outcomes of response in order to test for correlation with oximetry changes recorded early in the treatment course. Dartmouth College, through the Norris Cotton Cancer Center at the Dartmouth-Hitchcock Medical Center, has significant resources to leverage in order to conduct the proposed study. A group of investigators which includes clinical specialists in diagnostic radiology, surgical oncology, medical oncology, surgical pathology and medical engineering has been configured to develop and evaluate technology for breast imaging for cancer detection, diagnosis and therapy monitoring since 1999. The proposed project is an important component of the research of this group. In addition to the principal investigators, Professor Shudong Jiang and Dr. Peter A. Kaufman, MD, (Medical Oncology), Professors Keith D. Paulsen, Brian W. Pogue and Dr. Wendy A. Wells, MD, (Department of Pathology) will be significant collaborators engaged to accomplish the proposed specific aims, as an adjunct to currently funded grants involving breast imaging research. PUBLIC HEALTH RELEVANCE: This project will develop and evaluate dynamic Near-Infrared (NIR) tomographic oximetry for characterizing the response of locally advanced breast cancers to neoadjuvant chemotherapy by assessing the temporal variation in tumor oxygenation during hyperoxic gas inhalation. NIR oximetry acquired longitudinally during the course of therapy will be correlated with pathological endpoints in order to determine whether early prognostic biomarkers of treatment response can be identified in the dynamic NIR oxygenation signatures that could be used to customize breast cancer treatment decisions to individual patients in the future.