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

描述（由申请人提供）： 近红外（NIR）多光谱成像是用于表征女性乳房中的组织组成的独特工具。该模式的主要优点是能够提供组织氧饱和度（StO 2）以及总血红蛋白浓度（HbT）、水分数（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，因此评估其对新辅助化疗反应的变化可能会揭示治疗反应的早期预后生物标志物，这些生物标志物可用于在更个性化的患者基础上改变和/或优化治疗过程。用NIR光谱断层扫描评估高氧气体吸入后肿瘤氧合的动态对比度增强似乎是可行的，并且可以提供容易获得的低成本图像特征，用于预测乳腺中对化疗的治疗反应。本提案的总体目标是通过评估高氧气体吸入过程中肿瘤氧合的时间变化，开发和评价动态NIR断层扫描血氧测定法，以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%氧气之前和之后，最初较大且变化较快的肿瘤对新辅助化疗的临床反应更好。该假设将通过以下方式进行定量评估：1）推进当前NIR多光谱断层摄影系统，以对肿瘤内的动态氧合变化进行成像，所述动态氧合变化由呼吸100%氧气引起，具有0.1Hz图像帧速率，2）在治疗过程期间的不同时间对关于高氧吸入的肿瘤氧合响应进行定量，和3）量化响应的病理和临床结果，以测试与治疗过程早期记录的血氧测定变化的相关性。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，以进行拟议的研究。自1999年以来，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临床专家在内的一组研究人员已被配置为开发和评估用于癌症检测、诊断和治疗监测的乳腺成像技术。拟议的项目是该小组研究的一个重要组成部分。除了主要的研究者，蒋树东教授和彼得·A·考夫曼，医学博士（肿瘤内科），教授基思D.作者：Brian W. Pogue和Wendy A.医学博士威尔斯（病理学系）将是重要的合作者，致力于实现拟议的具体目标，作为目前资助的赠款涉及乳腺成像研究的辅助。公共卫生相关性：该项目将开发和评估动态近红外（NIR）断层血氧饱和度，通过评估高氧气体吸入期间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。在治疗过程中纵向采集的NIR血氧测定将与病理终点相关，以确定是否可以在动态NIR氧合特征中识别治疗反应的早期预后生物标志物，其可以用于在未来为个体患者定制乳腺癌治疗决策。

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.