Development of an intracoronary Raman spectroscopy

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2009.Includes bibliographical references (p. 167-177).Atherosclerosis is a leading cause of death in the United States, with 1 in 5 deaths (500,000 annually) attributable to coronary artery disease alone. While the disease processes are not completely understood, it is believed that patient risk depends on a variety of factors including lesion structure, biomechanical behavior, and morphological and chemical composition. Raman spectroscopy, based on spectral analysis of inelastically scattered photons, is a nondestructive technique that yields detailed information about the chemical composition of the sample being interrogated. Intracoronary Raman spectroscopy can be performed via the use of a flexible, small diameter (< 2 mm) optical fiber probe to guide light to and from the arterial wall in situ. The fact that Raman scattering has inherently low signal intensity, combined with the need for a small diameter probe, makes it difficult to develop a probe with sufficient signal-to-noise for robust plaque diagnosis. This thesis addresses two approaches for increasing SNR: increasing Raman signal intensity and optimizing probe design. While most biological applications of Raman spectroscopy have been performed in the "fingerprint" region (Raman shifts between 400 and 1800 cm-1), the high wavenumber region (2700 - 3100 cm-1) offers distinct technical advantages, including increased Raman signal relative to the fluorescent background and potentially less fiber background. However, the high wavenumber region may yield different molecular information and thus have different diagnostic capability. In this thesis, we develop a benchtop Raman system capable of acquiring Raman spectra in both wavenumber regions.(cont.) In contrast to previous work, which focused on plaque characterization based on the Raman spectrum from a single site within the plaque, our system utilizes a line imaging paradigm, in which we acquire Raman spectra at fixed intervals across the full cross-section of the plaque, creating a Raman line image. We use this benchtop system to acquire a database of Raman line images and corresponding histology for over sixty plaque specimens. Using this database, we compare the diagnostic capability of fingerprint and high wavenumber Raman spectroscopy for plaque characterization. Because of the small size requirement for an intracoronary probe, it is important to optimize the optical probe design to maximize collection efficiency and thus increase SNR. We develop and experimentally validate a simulation technique for modeling Raman probe performance (collection efficiency and sampling volume), as an aid to optimizing probe design. We also fabricate a 1.5 mm diameter probe and demonstrate it in vivo, using a human-swine xenograft model, in which diseased human coronary arteries are grafted onto a living swine heart. The results of this thesis provide insight on two approaches toward achieving a clinically viable intracoronary Raman spectroscopy system.by Alexandra H. Chau.Ph.D

Elastography using optical coherence tomography : development and validation of a novel technique

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2004.Includes bibliographical references (p. 161-167).Atherosclerosis is an inflammatory disease characterized by an accumulation of lipid and fibrous tissue in the arterial wall. Postmortem studies have characterized rupture-prone atherosclerotic plaques by the presence of a large lipid-rich core covered by a thin fibrous cap. Studies employing finite element analysis (FEA) based on ex vivo plaque geometry have found that most plaques rupture at sites of high circumferential stress, thus diagnosis of plaque vulnerability may be enhanced by probing the mechanical behavior of individual plaques. Elastography is a method of strain imaging in which an image sequence of the artery undergoing deformation is acquired, pixel motion is estimated between each frame, and the resulting velocity field is used to calculate strain. In this thesis, optical coherence tomography (OCT), a high-resolution optical imaging modality, is investigated as a basis for FEA and elastography of atherosclerotic plaques. FEA was performed using plaque geometries derived from both histology and OCT images of the same plaque. Patterns of mechanical stress and strain distributions computed from OCT-based models were compared with those from histology-based models, the current gold standard for FEA. The results indicate that the vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis. A new variational algorithm was developed for OCT elastography that improves upon the conventional algorithm by incorporating strain smoothness and incompressibility constraints into the estimation algorithm.(cont.) In simulated OCT images, the variational algorithm offers significant improvement in velocity and strain accuracy over the conventional algorithm, particularly in the presence of image noise. Polyvinyl alcohol (PVA) phantoms of homogeneous and heterogeneous elastic modulus distribution were developed for further testing of the variational algorithm. Testing with the phantoms indicated that motion- and strain-induced decorrelation between images presents a practical challenge to the implementation of OCT elastography. Analysis of the experimental results led to the identification of potential improvements to the elastography algorithm that may increase accuracy. These improvements may include relaxation of the strain smoothness constraint to incorporate strain discontinuities at boundaries of elastic modulus in heterogeneous regions, and enforcement of geometry compatibility to prevent the estimation of non-physical velocity fields.by Alexandra H. Chau.S.M

Elastography of coronary vessels using optical coherence tomography

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2002.Includes bibliographical references (leaf 32).by Alexandra H. Chau.S.B