Monitoring Neoadjuvant Chemotherapy Responses with NIR Tomography

描述(由申请人提供)：我们假设，过去15年来在达特茅斯开发和测试的新设计的便携式近红外光谱(NIRS)断层扫描版本可以成功地表征乳腺肿瘤血管和潜在的细胞代谢的变化，比目前正在研究的其他近红外光谱技术更准确，空间分辨率更高，更适合临床肿瘤学工作流程。近红外断层成像(NIRST)是一种独特的工具，用于表征女性乳房的组织成分，它可以生成总血红蛋白浓度(HBT)、组织氧饱和度(StO2)、含水率以及弹性散射参数的图像。根据以前的研究结果，这项建议的总体目标是开发和评估一种便携式和紧凑的NIRST系统，该系统有望更准确地量化HBT、StO2和水分的变化，作为接受新辅助化疗(NAC)的局部晚期乳腺癌治疗反应的早期指标，并将具有额外的波长，能够恢复脂质和胶原含量的新图像。将与最近完成的国家多中心(ACRIN)试验的手持漫反射光谱成像(DOSI)的结果进行比较。拟议的移动NIRST系统将整合到临床肿瘤学实践的工作流程中，以最大限度地增加患者的收益和参与拟议的研究，评估FLAIR反应的存在，并确定是否可以获得影响患者管理的预后信息。在用模体和正常受试者研究开发和验证新的便携式NIRST平台后，我们将通过1)成像与NAC不同治疗周期相关的输液前、中和后肿瘤血管的反应，以及2)量化NAC的反应的病理和临床结果，并将这些结果与NAC期间不同时间点测量的NIRST特性变化相关联，来定量评估我们的假说。该项目将推广通过已完成的NIH P01(P01-CA80139，Pi Paulsen)和R21(CA135303，Pi酱)拨款支持的研究中取得的成功初步成果。它还利用了我们为乳腺癌成像开发的广泛基础设施，十多年来，来自医学肿瘤学、外科病理学和生物医学光学工程的研究人员合作开发和评估了乳腺癌成像的先进技术。

DESCRIPTION (provided by applicant): We hypothesize that a newly redesigned portable tomographic version of Near Infrared Spectroscopy (NIRS), developed and tested at Dartmouth over the past 15 years, can successfully characterize changes in breast tumor vascularity, and potentially cellular metabolism, more accurately and with higher spatial resolution than other NIRS technologies currently under investigation, and is better suited to clinical oncology workflow. NIRS tomography (NIRST) is a unique tool for characterizing tissue composition in the female breast which generates images of total hemoglobin concentration (HbT), tissue oxygen saturation (StO2), water fraction, as well as elastic scattering parameters. Based on results obtained in previous studies, the overall goal of this proposal is to develop and evaluate a portable and compact NIRST system that is expected to quantify changes in HbT, StO2 and water fraction more accurately as early indicators of treatment response of locally advanced breast cancers receiving neoadjuvant chemotherapy (NAC), and will have additional wavelengths enabling the recovery of new images of lipid and collagen content. Comparisons to results obtained with hand- held Diffuse Optical Spectroscopic Imaging (DOSI), which has undergone a recently-completed national multi- center (ACRIN) trial, will occur. The proposed mobile NIRST system will integrate into the workflow of clinical oncology practice to maximize patient accrual and participation in the proposed studies, assess the presence of a flair response, and determine whether prognostic information can be obtained that would influence patient management. After developing and validating the new portable NIRST platform with phantom and normal- subject studies, we will quantitatively assess our hypothesis by 1) imaging the response of tumor vasculature before, during and after infusions associated with different treatment cycles of NAC, and 2) quantify pathological and clinical outcomes of response to NAC, and relate these outcomes to changes in NIRST properties measured at different time points during NAC. The project will extend successful preliminary results obtained in studies supported through completed NIH P01 (P01-CA80139, PI Paulsen) and R21 (CA135303, PI Jiang) grants. It also leverages the extensive infrastructure we have developed for breast cancer imaging where investigators from medical oncology, surgical pathology and biomedical optical engineering have collaborated to develop and evaluate advanced technology for breast cancer imaging for more than a decade.