MONITORING CHEMOTHERAPY RESPONSE BY PHOTON MIGRATION SPECTROSCOPY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。局部晚期乳腺癌(LABC)患者的最佳治疗仍然是一个复杂的治疗问题。乳癌占美国所有新诊断的乳腺癌的5%-20%，在医疗服务不足的地区发病率较高。多年来，LABC的治疗方法一直在演变，从接受根治性乳房切除术到使用新辅助化疗，然后再进行乳房切除术或保乳治疗。由于难以评估治疗反应，LABC新辅助化疗的最佳强度和持续时间仍然存在争议。目前，对治疗的反应是通过体检、乳房X光检查和/或超声波来衡量的。几项研究表明，新辅助化疗的临床评估或反应与治疗后手术标本中发现的反应的病理评估之间存在显著差异。类似的研究表明，与手术时残留肉眼疾病的患者相比，病理肉眼完全缓解的患者预后更好。因此，确定LABC局部手术治疗的最佳时机是非常重要的。其目标将是防止新辅助化疗患者的过度和不足治疗。许多成像设备都在研究这一特定问题，如正电子发射断层扫描(PET)和增强磁共振成像(MRI)，但这些设备昂贵、复杂，而且对普通公众的接触有限。在正常志愿者和接受化疗的患者身上，一种名为光子迁移光谱(PMS)的非侵入性技术的初步结果显示，对乳房组织功能变化具有极高的敏感性。在LABC受试者中，这些变化与总体肿瘤尺寸的减少有关。光子迁移光谱是一种非侵入性的光学技术，它利用强度调制的近红外(NIR)光来定量测量厚组织的光学性质。由PMS测量得出的光学特性(吸收、US和散射US参数)可用于构建低分辨率(0.5-1厘米)的组织血红蛋白(总、氧和脱氧形式)、血氧饱和度、血容量分数、水分含量、脂肪含量和细胞结构的功能图像。与传统的近红外透照不同，PMS可以在一次非侵入性测量中对组织的吸收和散射参数进行定量分析。PMS所提供的独特的功能信息使其非常适合于描述厚组织中的肿瘤。使用非侵入性、多波长、半导体激光PMS设备进行测量。一些初步结果表明，在接受新辅助化疗的局部晚期乳腺癌肿瘤中，可以检测到利用光子迁移技术进行治疗的代谢变化。这些测量提供了反映组织灌注量、氧气消耗和细胞/基质发育变化的定量光学属性值。我们的初步研究将对接受新辅助化疗的乳腺癌患者的肿瘤进行序贯光子迁移光谱分析(PMS)。PMS读数将在每个化疗周期之前和之后获得。同时，还将收集乳腺肿瘤的同步基线体检、常规实验室、脉搏血氧饱和度和超声测量结果。对接受新辅助化疗的患者的常规护理标准中获得的前新辅助化疗和术后肿瘤样本，将进行免疫组织病理学检查。所有这些数据都将用统计模型进行分析，看看PMS能否准确地确定和量化接受化疗的乳腺癌肿瘤的生理参数，以及手术标本中仍存在的残留病变量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Optimal management of patients with locally advanced breast cancer (LABC) remains a complex therapeutic problem. LABC represents 5-20% of all newly diagnosed breast cancers in the United States with a higher incidence in medically underserved areas. Over the years, treatment for LABC has been evolving from undergoing a radical mastectomy to the use of neoadjuvant chemotherapy followed by a mastectomy or breast conservation therapy. The optimal intensity and duration of neoadjuvant chemotherapy for LABC still remains controversal due to the difficulty of evaluating response to therapy. Presently, response to treatment is measured by physical exam, mammography, and/or ultrasound. Several studies have showed significant discrepancies between the clinical assessment or response to neoadjuvant chemotherapy and the pathologic assessment of response found in post-therapy surgical specimens. Similar studies have shown that patients achieving pathologic macroscopic complete response have a better prognosis that those patients left with residual macroscopic disease at the time of surgery. Consequently, it is very important to determine the optimal timing of the local surgical treatment of LABC patients. The goal would be to prevent over and under treatment of patients with neoadjuvant chemotherapy. Many imaging modalities are investigating this specific problem such as positron emission tomography (PET) and contrast enhanced magnetic resonance imaging (MRI) but these modalities are expensive, complex, and have limited access to the general public. Preliminary results with a non-invasive technique, Photon Migration Spectroscopy (PMS), on normal volunteers and patients receiving chemotherapy have shown excellent sensitivity to breast tissue functional changes. These changes were correlated with a decrease in overall tumor dimensions in the cases of LABC subjects. Photon Migration Spectroscopy is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, us and scattering us' parameters) derived from PMS measurements can be used to construct low-resolution (0.5-1 cm) functional images of tissue hemoglobin (total, oxy, and deoxy forms), oxygen saturation, blood volume fraction, water content, fat content, and cellular structure. Unlike conventional NIR transillumination, PMS enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by PMS makes it well suited to characterizing tumors in thick tissues. Measurements are performed using a non-invasive, multi-wavelength, diode-laser PMS device. Some preliminary results show that the metabolic changes are detectable in locally advanced breast cancer tumors undergoing treatment with neoadjuvant chemotherapy using photon migration techniques. The measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development. Our pilot study will be to perform sequential Photon Migration Spectroscopy (PMS) on tumors of breast cancer patients undergoing neoadjuvant chemotherapy. PMS readings will be obtained prior to and subsequent to each chemotherapy cycle. Concurrent, baseline physical exams, routine labs, pulse oximetry, and ultrasound measurements of the breast tumor will also be collected. Immunohistopathology will be performed on both the pre-neoadjuvant chemotherapy and the post-surgical tumor samples which are obtained in the routine standard of care for patients undergoing neoadjuvant chemotherapy. All this data will be then analyzed with statistical models to see whether PMS can determine accurately and quantify the physiological parameters of breast cancer tumors undergoing chemotherapy and the amount of residual disease still present in the surgical specimen.