Near infrared autofluorescence augmentation of optical coherence tomography for diagnosis of coronary atherosclerosis
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Coronary artery disease accounts for nearly 50% of cardiovascular disease, the leading cause of death in the United States. The progression of atherosclerotic plaque is not yet fully understood. Histopathologic analysis of cadaver coronary plaques has suggested that certain subsets of coronary lesions, the vulnerable plaques, predispose patients to myocardial infarction. Prospective identification and treatment of vulnerable plaques has emerged as an important future goal for intravascular imaging and intervention. However, no single imaging modality has been shown to be capable of definitively identifying these lesions. Optical coherence tomography is a catheter-based imaging method that rapidly acquires three-dimensional images of coronary artery wall microstructure. While OCT has been documented to be capable of visualizing morphologic features associated with vulnerable plaques, it has not been shown to identify necrotic core or other putative chemicals/molecules associated with plaque progression and rupture. One solution is to add a secondary modality to OCT which detects molecules specific to necrotic cores. While conducting bench top spectroscopy measurements, our laboratory discovered that the intensity of near-infrared autofluorescence (NIRAF) is associated with plaque types. Using benchtop spectroscopy, this dissertation research established the relationship between the NIRAF signal intensity and spectral shape and atherosclerosis, and demonstrated its potential to differentiate necrotic core plaques from other arterial lesions. In addition to these spectroscopy-disease correlations, this thesis describes research conducted to identify the chemical/molecular origin of the NIRAF signal, using histopathology, confocal microscopy, spectroscopy, and chemical synthesis. The results indicate that protein modification in necrotic core is a potential mechanism for high NIRAF in advanced plaques. To translate OCT-NIRAF clinically, this dissertation describes the design of a double clad fiber that enables catheter-based detection of both OCT and NIRAF and a safety study to demonstrate that NIRAF excitation does not damage the artery wall. A preclinical OCT-NIRAF catheter was fabricated and used to image human coronary arteries ex vivo. These data showed that vulnerable plaques can potentially be identified using intracoronary OCT-NIRAF. The sum total of results from this thesis reseatch demonstrate the feasibility of conducting OCT-NIRAF imaging in human patients for the prospective identification ofvulnerable coronary plaques.
Thesis (Ph.D.)--Boston University