Real-Time Optical Diagnosis of Inflammatory Bowel Disease using SFDI

描述(申请人提供)：炎症性肠病(IBD)诊断和治疗中的一个基本问题是实时识别可能发生在胃肠道(GI)大片区域的病变。目前的护理标准包括通过彩色电视显微镜进行目视检查，组织外观和彩色引导活检和临床决策。鉴于仅在美国，IBD的患病率就超过140万人，而且在病程早期进行干预可以防止发病率，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。指导这项研究的假设是，穿透肠粘膜几毫米的近红外(NIR)光，结合结构照明的最新进展，将能够实时量化组织光学特性，包括结肠镜检查期间的灌流、水化和代谢，从而改进IBD的检测。虽然光学相干层析成像(OCT)、散射光谱和吸收光谱等其他光学技术已经被应用于IBD的识别，但没有一种技术提供大范围(数十平方厘米)和非接触配置下的光学性质的量化。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高速、非接触式成像。使用多光谱空间频域成像(SFDI)，现在可以量化还原的散射和吸收参数，以及生色团的氧合血红蛋白、脱氧血红蛋白、水和脂质。然而，SFDI在诸如结肠镜检查和腹腔镜检查等微创技术中的应用尚未被尝试，因为在组织曲率的校正和具有适当空间频率内容的与纤维镜兼容的结构照明的产生方面存在巨大的技术挑战。这项K01应用的具体目标集中在：1)开发从简化的光模式中提取发色团浓度所需的光学理论，2)设计针对同时进行彩色视频成像(即护理标准)和SFDI而优化的结肠镜投影和采集系统，以及3)开发由各种组织光学属性组成的光学度量，该光学度量可以在疾病的小鼠模型中预测IBD。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。BIDMC在Frangion博士的指导下以及Beckman激光研究所在Tromberg博士的指导下提供的学术环境是实现这一目标的理想选择。为了更好地响应临床医生的需求，应聘者需要更多地了解临床工作环境，为了扩大自己的专业知识，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诊断中的一个长期问题，同时培训候选人成为一名独立的调查员。为了实现这一具有挑战性的目标，我们组建了一支强大而敬业的指导团队，具体内容如下：姓名、角色、对该项目的贡献摘要。导师Frangion教授将在临床翻译和生物医学工程方面提供具体的教学。他 还将提供实验室管理和职业发展方面的教学。布鲁斯·J·特伦伯格博士共同导师特伦伯格教授将提供生物医学光学理论方面的具体教学，重点是结构照明和光谱分析等先进技术。临床顾问Chuttani博士将在胃肠病临床工作流程、IBD筛查和视频内窥镜/纤维内窥镜检查的当前护理标准方面提供具体教学。临床顾问罗伯特·D·奥兹教授将在IBD组织病理学和疾病发展方面提供具体教学。他还将帮助将光学结果与组织学结果相关联。Long Ngo，博士顾问Ngo博士将 提供生物统计学和研究设计方面的具体教学。特别是，他将帮助进行差热分析，以创建和验证拟议的光学IBD指数。总之，这份K01申请为申请者描述了一种培训工具，该申请者在术中成像方面有很强的背景，但在内源性漫反射光学、动物研究和临床纤维镜检查方面经验相对较少。导师的实验室在光学技术的临床翻译方面有着良好的记录。这位合作导师的实验室在生物医学光学理论方面拥有专业知识。在这种学术环境下，K01的申请描述了一个职业发展计划和机构承诺，允许候选人在五年的时间内过渡到独立，同时他对具有深远临床意义的研究领域做出了贡献。

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.