Monitoring Neoadjuvant Chemotherapy Responses with NIR Tomography

描述（申请人提供）：我们假设，在过去的15年里，达特茅斯开发和测试的新重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分布的变化，以及潜在的细胞代谢，比目前正在研究的其他NIRS技术更准确，空间分辨率更高，并且更适合于临床肿瘤学工作流程。近红外线断层扫描（NIRST）是一种独特的工具，用于表征女性乳房中的组织成分，可生成总血红蛋白浓度（HbT）、组织氧饱和度（StO 2）、水分分数以及弹性散射参数的图像。基于先前研究中获得的结果，本提案的总体目标是开发和评估便携式紧凑型NIRST系统，该系统有望更准确地量化HbT、StO 2和水分含量的变化，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，并具有额外的波长，能够恢复脂质和胶原蛋白含量的新图像。将与最近完成的国家多中心（ACRIN）试验的手持式漫射光学光谱成像（DOSI）获得的结果进行比较。拟议的移动的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参与拟议研究的人数，评估是否存在天赋反应，并确定是否可以获得影响患者管理的预后信息。在开发和验证具有体模和正常受试者研究的新型便携式NIRST平台之后，我们将通过以下方式定量评估我们的假设：1）在与NAC的不同治疗周期相关的输注之前、期间和之后对肿瘤脉管系统的响应进行成像，以及2）量化对NAC的响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。该项目将扩展通过已完成的NIH P01（P01-CA 80139，PI Paulsen）和R21（CA 135303，PI Jiang）赠款支持的研究中获得的成功初步结果。它还利用了我们为乳腺癌成像开发的广泛基础设施，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已经合作开发和评估了十多年的乳腺癌成像先进技术。

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.