Real-Time Optical Diagnosis of Inflammatory Bowel Disease using SFDI

描述（由申请人提供）：炎症性肠病（IBD）诊断和管理的一个基本问题是实时识别可能发生在胃肠道（GI）大面积的病变。目前的护理标准包括通过彩色视像镜进行视觉检查，组织外观和颜色指导活检和临床决策。仅在美国，IBD的患病率就超过140万，而且在病程早期进行干预可以预防发病率，因此迫切需要新的工具来提高诊断准确性、量化疾病负担和监测治疗效果。指导本研究的假设是，近红外（NIR）光可以穿透几毫米进入肠粘膜，结合最近的结构化照明进展，将允许在结肠镜检查过程中实时定量组织光学特性，包括灌注、水合作用和代谢，从而提高IBD的检测。尽管其他光学技术，如光学相干层析成像（OCT）、散射光谱和吸收光谱已经应用于IBD的鉴定，但没有一种技术可以在宽视场（数十平方厘米）和非接触结构中提供光学特性的量化。导师和共同导师实验室的最新发展提供了开放手术期间组织光学特性的超快速、非接触式成像。利用多光谱空间频域成像（SFDI），可以量化减少的散射和吸收参数，以及氧血红蛋白、脱氧血红蛋白、水和脂质发色团。然而，由于在校正组织曲率和生产具有适当空间频率含量的纤维镜兼容结构照明方面存在巨大的技术挑战，SFDI尚未尝试应用于微创技术，如结肠镜和腹腔镜。本K01应用程序的具体目标集中在：1)发展从简化的光模式中提取发色团浓度所需的光学理论；2)设计一种优化的结肠镜投影和采集系统，用于同时进行彩色视频成像（即护理标准）和SFDI； 3)开发一种由各种组织光学特性组成的光学度量，用于预测IBD小鼠模型中的疾病。候选人/导师/环境：候选人的长期职业目标是开发用于临床的新型生物医学技术和设备，以改善患者管理。在弗朗吉奥尼博士指导下的BIDMC学术环境，以及在特龙伯格博士指导下的贝克曼激光研究所，都是实现这一目标的理想场所。为了更好地响应临床医生的需求，候选人需要更多地了解临床工作环境，为了扩大他的专业知识，候选人需要在生物医学光学理论方面进行高级培训。K01项目旨在解决IBD诊断中长期存在的问题，同时培养候选人成为独立研究者。为了实现这一具有挑战性的目标，我们组建了一个强大而专注的指导团队，如下所述：名称角色项目贡献总结John V. Frangioni，医学博士，博士导师Frangioni教授将提供临床翻译和生物医学工程方面的具体教学。他

DESCRIPTION (provided by applicant): A fundamental problem in the diagnosis and management of inflammatory bowel disease (IBD) is the real-time identification of lesions that can occur over large areas of the gastrointestinal (GI) tract. The standard of care presently consists of visual examination through a color videoscope, with tissue appearance and color guiding biopsy and clinical decision making. Given that IBD has a prevalence of over 1.4 million patients in the US alone, and intervention early in the disease course prevents morbidity, new tools to improve diagnostic accuracy, quantify disease burden, and monitor treatment efficacy are desperately needed. The hypothesis guiding this study is that near-infrared (NIR) light, which penetrates several millimeters into the intestinal mucosa, combined with recent advances in structured illumination, will permit real-time quantification of tissue optical properties, inclding perfusion, hydration, and metabolism during colonoscopy, thus improving IBD detection. Although other optical techniques such as optical coherence tomography (OCT), scattering spectroscopy, and absorption spectroscopy have already been applied to the identification of IBD, none provide quantification of optical properties in a wide field (tens of cm2) and non-contact configuration. Recent developments in the mentor's and co-mentor's laboratories provide ultra-fast, non-contact imaging of tissue optical properties during open surgery. Using multispectral spatial frequency domain imaging (SFDI), quantification of reduced scattering and absorption parameters, as well as the chromophores oxyhemoglobin, deoxyhemoglobin, water, and lipid, is now possible. Application of SFDI to minimally invasive techniques, such as colonoscopy and laparoscopy, however, has not yet been attempted because of formidable technical challenges in the correction of tissue curvature and in the production of fiberscope- compatible structured illumination having the proper spatial frequency content. The Specific Aims of this K01 application focus on: 1) developing the optical theory necessary for extracting chromophore concentration from simplified patterns of light, 2) designing a colonoscope projection and acquisition system optimized for simultaneous color video imaging (i.e., the standard of care) and SFDI, and 3) developing an optical metric comprised of various tissue optical properties that is predictive of IBD in a mouse model of the disease. Candidate / Mentors / Environment: The candidate's long-term career goal is to develop novel biomedical technologies and devices that are used in the clinic to improve patient management. The academic environment available at the BIDMC under Dr. Frangioni's guidance, and at the Beckman Laser Institute under Dr. Tromberg's guidance, are ideal for reaching this goal. In order to better respond to needs of clinicians, the candidate needs to learn more about the clinical work environment, and in order to expand his expertise, needs advanced training in biomedical optics theory. The K01 project aims at solving a longstanding problem in IBD diagnosis while training the candidate to become an independent investigator. To achieve this challenging goal, a strong and dedicated mentoring team has been assembled as follows: Name role Summary of the contributions to the project John V. Frangioni, M.D., Ph.D. Mentor Prof. Frangioni will provide specific teaching in clinical translation & biomedical engineering. He will also provide teaching in laboratory management and career development. Bruce J. Tromberg, Ph.D. Co-Mentor Prof. Tromberg will provide specific teaching in biomedical optics theory with a particular focus on advanced techniques such as structured illumination and spectroscopy. Ram Chuttani, M.D. Clinical Consultant Dr. Chuttani will provide specific teaching in gastroenterology clinical workflow, current standard of care in IBD screening and videoendoscopy/fiberoscopy. Robert D. Odze, M.D. Clinical Consultant Prof. Odze will provide specific teaching in IBD histopathology and disease development. He will also help in correlating the optical results with histological findings. Long Ngo, Ph.D. Consultant Dr. Ngo will provide specific teaching in biostatistics and study design. In particular, he will help with the dta analysis for creating and validating the proposed optical IBD index. In summary, this K01 application describes a training vehicle for an applicant with a strong background in intraoperative imaging but with relatively little experience in endogenous diffuse optics, animal studies, and clinical fiberoscopy. The mentor's laboratory has a proven track record in clinical translation of optical technology. The co-mentor's laboratory has expertise in biomedical optics theory. Within this academic environment, the K01 application describes a career development plan and institutional commitment that will permit the transition of the candidate to independence over a period of five years, while he simultaneously contributes to an area of investigation with profound clinical significance.