Early Non-Invasive Diagnosis of Liver Disease with Optical Spectroscopy

由于缺乏准确的非侵入性临床测试，肝病患者的临床管理是一个重大挑战。一些药物已经显示出逆转肝纤维化和肝硬变的希望，然而，在人体上测试这些药物存在很大的障碍，因为治疗评估需要有创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，并将在肝病学中产生广泛的影响。该项目将为哈佛医学院的生物和生物医学(BBS)项目学生以及哈佛-麻省理工学院健康科学与技术部门(HST)的学生提供博士论文项目。PI将增加哈佛大学的课程，介绍漫反射光学光谱学的原理。部分仪器开发和设计将由PI提供给在波士顿大学教授的生物医学工程高级设计课程中的学生项目。PI已经表明，光学光谱可以通过量化血红蛋白、细胞色素、脂肪和胶原的散射和吸收特性来获得小鼠肝脏诊断信息。为了进行人类使用，该项目将开发非侵入性的光学光谱方法，将这些特性的变化与肝脏疾病关联起来，目的是提供一种适合人类的准确诊断方法。首先，动物使用的技术将允许研究所有适用的肝病模型的诊断参数。然后，他们将开发一种非侵入性的临床光学光谱系统，并在人体内对其进行测试。这包括开发一种非侵入性光纤探头，通过测量与门脉高压相关的光谱参数来检测肝病。数值模拟将使用蒙特卡罗技术来模拟光在介质层中的传播。在多层模型上的实验测量将被用来验证模型。具体任务包括：(1)组织体模的仪器开发和测试；(2)非侵入性活体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.