The 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.

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Beth Israel Deaconess Medical Center
United States
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