Early Non-Invasive Diagnosis of Liver Disease with Optical Spectroscopy

佩雷尔曼1605116由于缺乏准确的非侵入性临床检测，肝病患者的临床管理是一项重大挑战。一些药物已经显示出逆转肝纤维化和肝硬化的前景，但是在人体中测试这些药物存在很大的障碍，因为治疗评估需要侵入性肝活检或尸检评估。该项目将开发一种用于非侵入性肝脏监测的光学光谱系统，并将在肝脏病学中产生广泛的影响。该项目将提供博士学位。为哈佛医学院生物和生物医学科学（BBS）项目的学生以及哈佛-麻省理工学院健康科学与技术部（HST）的学生提供论文项目。PI将增加哈佛的课程，介绍漫射光谱学的原理。仪器开发和设计的部分将由PI提供，用于BU指导的生物医学工程高级设计课程中的学生项目。PI已经表明，光谱学可以通过量化由于血红蛋白、细胞色素、脂肪和胶原蛋白的散射和吸收特性来获得小鼠的肝脏诊断信息。为了进行人类使用，该项目将开发非侵入性光谱方法，用于将这些特性的改变与肝脏疾病相关联，目的是提供适合人类的准确诊断方法。第一种用于动物的技术将允许在所有适用的肝病模型中研究诊断参数。然后，他们将开发一种非侵入性临床光谱系统，并在人体内进行测试。这涉及开发一种非侵入性的基于光纤的探针，通过测量与门静脉高压相关的光谱参数来检测肝脏疾病。数值模拟将使用蒙特卡罗技术来模拟光通过介质层的传播。多层幻影的实验测量将用于验证模型。具体任务包括：（1）组织活检中的仪器开发和测试;（2）非侵入性体内测量的物理模型和算法;以及（3）动物和人体实验。

ABSTRACTPerelman, Lev; 1605116The clinical management of patients with liver disease is a major challenge due to the absence of accurate non-invasive clinical tests. Some medications have shown promise for reversing liver fibrosis and cirrhosis, however there is a large barrier in testing these medications in people because treatment evaluation requires either invasive liver biopsy or post-mortem evaluation. This project will develop an optical spectroscopic system for non-invasive liver monitoring and will have a broad impact in hepatology. The project will provide Ph.D. thesis projects for Biological and Biomedical Sciences (BBS) Program students at Harvard Medical School and also the Harvard-MIT Division of Health Sciences and Technology (HST) students. The PI will augment courses at Harvard to introduce the principles of diffuse optical spectroscopy. Portions of instrument development and design will be made available by the PI for student projects within the biomedical engineering senior design course instructed at BU. The PI has shown that optical spectroscopy can obtain liver diagnostic information in mice by quantifying scattering and absorption properties due to hemoglobin, cytochromes, fat, and collagen. In order to proceed to human use the project will develop non-invasive optical spectroscopic methods for correlating alterations in these properties with liver disease, with the goal of providing an accurate diagnostic method appropriate for humans. First techniques for animal use will allow studying diagnostic parameters in all the applicable models of liver disease. Then they will develop a non-invasive clinical optical spectroscopy system and will test it in vivo in human subjects. This involves development of a non-invasive fiber based probe for liver disease by measuring spectroscopic parameters related to portal hypertension. Numerical modeling will use Monte Carlo techniques to model light propagation through media layers. Experimental measurements on multilayered phantoms will be used to validate the models. Specific tasks include: (1) Instrumentation Development and Testing in Tissue Phantoms; (2) Physical Model and Algorithm for Non-Invasive in Vivo Measurements; and (3) Animal and Human Experiments.