Multi-Spectral Parallel-Plate Diffuse Optical Breast Tomography

描述（由申请人提供）：该竞争性延续提案的长期目标是评估和提高近红外（NIR）光漫射光学断层扫描（DOT）的乳腺肿瘤筛查、诊断和监测能力。近红外漫射光学断层扫描是基于功能过程的研究，并提供了几个独特的可测量的参数，有可能提高乳腺癌检测和表征的灵敏度和特异性。具体而言，DOT提供与肿瘤病理生理学直接相关的功能信息（例如，代谢活性、血管生成和血流/浓度）。该信息可以补充由传统医学成像提供的结构和功能信息。此外，与许多诊断方法不同，DOT技术利用非电离辐射，是非侵入性的，并且通常技术上简单快速。因此，随着更多的信息被获取和分析，我们期望漫射光学在筛查、诊断和癌症治疗监测中找到各种利基应用。拟议的研究建立在初步成功的基础上，旨在通过实施新的统计分析方法，通过检查组织病理学和光学肿瘤特征之间的关联，通过将改进的第二代仪器引入临床，以及通过探索外源性造影剂成像和新辅助化疗监测的试点临床研究，继续改进和探索DOT。拟议的研究将从正在进行的临床试验和宾夕法尼亚大学医院（HUP）的正常患者人群中获得患者。该研究包括开发乳腺DOT计算机辅助检测（CAD）分析和软件;此外，还计划进行一系列患者密集型（而不是探索性）临床试验。主要临床研究（约100例患者，50例正常受试者）将基于内源性造影剂采集正常和荷瘤患者的数据。初步临床研究将在新辅助化疗期间跟踪肿瘤进展（约25例患者，25例正常受试者），并将测量外源性造影剂吲哚菁绿色冲洗入和冲洗出荷瘤乳腺时的荧光（约50例患者，25例正常受试者）。总体而言，该项目将提供设计更全面的未来DOT临床试验所需的基本信息。公共卫生相关性：在美国，大约八分之一的女性会患上乳腺癌，其中大约30%的人最终会死于这种疾病。尽管有相当大的科学进步，但仍然需要新技术来更早地检测乳腺癌以进行治疗，检测被筛查性乳房X线摄影遗漏的癌症，改进在选定情况下的癌症诊断和分期，以及在癌症治疗期间跟踪肿瘤进展并协助治疗规划。这项资助的长期目标是评估和提高近红外光扩散光学断层扫描的乳腺肿瘤筛查、诊断和监测能力。

DESCRIPTION (provided by applicant): The long-range goal of this competing continuation proposal is to assess and improve the breast tumor screening, diagnostic and monitoring capabilities of diffuse optical tomography (DOT) with near infrared (NIR) light. Near-infrared diffuse optical tomography is based on the study of functional processes and provides several unique measurable parameters with potential to enhance breast cancer detection and characterization sensitivity and specificity. In particular, DOT provides functional information directly related to tumor patho- physiology (e.g. metabolic activity, angiogenesis, and blood flow/concentration). This information can be complementary to structural and functional information provided by traditional medical imaging. Furthermore unlike many diagnostic methods, DOT techniques utilize non-ionizing radiation, are non-invasive, and are often technologically simple and fast. Thus, as more information is acquired and analyzed, we expect diffuse optics to find a variety of niche applications in screening, diagnosis and cancer therapy monitoring. The proposed research builds on initial success and aims to continue to improve and explore DOT by implementing novel statistical analysis methods, by examining associations between histopathology and optical tumor signatures, by introducing a much-improved Generation II instrument into the clinic, and via pilot clinical studies exploring exogenous contrast agent imaging and neoadjuvant chemotherapy monitoring. The proposed research will derive patients from ongoing clinical trials and from the normal patient population at the Hospital of the University of Pennsylvania (HUP). The research includes the development of breast-DOT computer aided detection (CAD) analyses and software; in addition a range of patient-intensive (rather than exploratory) clinical trials are planned. Primary clinical studies (~100 patients, 50 normal subjects) will acquire data from normal and tumor bearing patients based on endogenous contrast. Pilot clinical studies will follow tumor progression during neoadjuvant chemotherapy (~25 patients, 25 normal subjects) and will measure fluorescence from an exogenous contrast agent, Indocyanine Green, as it washes into and out-of the tumor bearing breast (~50 patients, 25 normal subjects). Overall, the project will provide basic information needed for the design of more comprehensive, future DOT clinical trials. PUBLIC HEALTH RELEVANCE: Approximately one in eight women in the United States will develop breast cancer, and of these about 30% will ultimately die of the disease. Despite considerable scientific progress, new technologies are still desirable to detect breast cancers earlier for treatment, to detect cancers missed by screening mammography, to improve cancer diagnosis and staging in selected situations, and to track tumor progression during cancer therapy and to assist in therapy planning. The long-range goal of this grant is to assess and improve the breast tumor screening, diagnostic and monitoring capabilities of diffuse optical tomography with near infrared light.