BME PhD Dissertation Defense - Hao Wang

10:00 am on Friday, July 25, 2014
44 Cummington Mall, Room 401

Professor Joyce Wong (Chair)
Professor Guillermo Tearney (Research Advisor, MGH/Harvard Medical School)
Professor Jerome Mertz (BME Co-Advisor)
Professor Irving Bigio
Professor James Hamilton

Coronary artery disease attributes to almost 50% percent of heart disease, which is the top one leading cause of death in the United States and the western world. As the fundamental problem, the progression of atherosclerotic plaque is not yet fully understood. Pathology study provides the current division of plaque stages and points out the concept of plaque vulnerability as a goal for medical imaging and interventional cardiology. No imaging modality alone is adequate to reveal plaque vulnerability, since the plaque progression is a comprehensive process with structural, biochemical and mechanical changes.

Optical coherence tomography is a non-invasive, high resolution and fast imaging tool to acquire microscopic structural features of coronary plaques. Its capability to evaluate plaque vulnerability is limited by optical penetration depth on lipid rich plaques and imaging artifacts due to tissue irregularity. To evaluate plaque vulnerability, it is very important to add a secondary modality to OCT, which can differentiate necrotic core plaques from lipid containing non-necrotic plaques.

MGH Tearney lab have been investigating Raman spectroscopy to acquire plaque compositional information. However, the Raman signal is often overwhelmed by near infrared autofluorescence. Using benchtop spectroscopy measurement, this dissertation established the correlation between near infrared autofluorescence and atherosclerosis, which provided potential to highlight necrotic core plaques on human coronary.

To translate the benchtop measurement into a clinical device, this dissertation describes the challenges, efforts and solutions to design a double clad fiber, which enables catheter-based detection of NIRAF. A preclinical catheter was fabricated and applied for ex vivo human coronary imaging by OCT-NIRAF combination. The results demonstrated the feasibility to do OCT-NIRAF imaging in human patients. Further, the laser exposure safety was evaluated on a test system. The results suggested that the current OFDI-NIRAF scheme doesn’t cause damage to arterial tissue.

Besides correlation with the disease, this dissertation provided different clues to discuss the nature of NIRAF, including histopathology staining, confocal microscopy, spectroscopy measurement and chemical synthesis. Protein modification in the necrotic core region was suggested as a potential mechanism.