No abstract

Laser angioplasty, or the ablation of atherosclerotic plaque using laser energy, has tremendous potential to expand the scope of nonsurgical treatment of obstructive vascular disease. Clinical laser angioplasty, however, has been hindered by an unacceptable risk of vessel perforation. Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal artery and may therefore be capable of guiding selective plaque ablation. To assess the feasibility of utilizing spectral information to discriminate arterial tissue type, several classification algorithms were developed and evaluated. Arterial fluorescence spectra from 350 to 700 nm were obtained from 100 human aortic specimens. Seven spectral classification algorithms were developed with the following techniques: multivariate linear regression, stepwise multivariate linear regression, principal components analysis, decision plane analysis, Bayes decision theory, principal peak ratio, and spectral width. The classification ability of each algorithm was evaluated by its application to the training set and to a validation set containing 82 additional spectra. All seven spectral classification algorithms prospectively classified atherosclerotic and normal aorta with an accuracy greater than 80 percent (range: 82-96 percent). Laser angioplasty systems incorporating spectral classification algorithms may therefore be capable of detection and selective ablation of atherosclerotic plaque.

Laser-induced fluorescence (LIF) spectroscopy can only be used for laser angioplasty guidance if high-power laser ablation does not significantly alter the pattern of tissue fluorescence. Although the spectra of normal and atherosclerotic arteries differ, the change in fluorescence spectra following laser angioplasty has not been well studied. Therefore, the purpose of this study was to assess whether laser-induced fluorescence spectroscopy could guide selective laser ablation of atherosclerotic plaque and, if so, to develop a quantitative LIF score that could be used to control a "smart" laser angioplasty system. Baseline LIF spectroscopy of 50 normal and 50 atherosclerotic human aortic specimens was performed using an optical fiber coupled to a He-Cd laser and optical multichannel analyzer. LIF was then serially recorded during erbium:YAG laser ablation of 27 atherosclerotic specimens. Laser ablation was terminated when the arterial LIF spectrum visually appeared normal. Histologic analysis revealed a mean initial plaque thickness of 1,228 +/- 54 microns and mean residual plaque thickness of 198 +/- 27 microns. Ablation of the media occurred in only three specimens. A discriminant function was derived to discriminate atherosclerotic from normal tissue for computer guidance of laser angioplasty. The LIF score, derived from stepwise multivariate linear regression analysis of the LIF spectra, correctly classified 93% of aortic specimens. The spectra obtained from the atherosclerotic specimens subjected to fluorescence-guided laser revealed a change in score from "atherosclerotic" to "normal" following plaque ablation. Seven atherosclerotic specimens were subjected to laser angioplasty with on-line computer control using the LIF score. Mean initial plaque thickness was 1,014 +/- 86 microns, and mean residual plaque thickness was 78 +/- 29 microns. There was no evidence of ablation of the media. Therefore, LIF guidance of laser ablation resulted in minimal residual plaque without arterial perforation. These findings support the feasibility of an LIF-guided laser angioplasty system for selective atherosclerotic plaque ablation.

Laser-induced fluorescence spectroscopy can be used to discriminate between normal and atherosclerotic tissue and guide the delivery of high-power laser energy for laser angioplasty. The depth of tissue from which fluorescence is measured should closely match the depth of laser ablation and, from a practical standpoint, should be neither too small nor too large. This paper investigates the depth of the fluorescence signal. A simple mathematical model is presented. An experimental procedure for determining this depth is described. The results agree well with the model. The implications of the findings to the development of a practical fluorescence-guided laser angioplasty system are discussed.

Analysis of the change in arterial fluorescence during plaque ablation may provide the basis for developing a fluorescence-guided ablation system capable of selective plaque ablation without risk of vessel perforation. Accordingly, fluorescence spectra were recorded from 91 normal and 91 atherosclerotic specimens of cadaveric human aorta. The ratio of the laser-induced fluorescence intensity at 382 nm to 430 nm (LIF ratio) was capable of classifying these specimens with an 89% accuracy with a threshold value of 1.8 (atherosclerotic greater than or equal to 1.8, normal less than 1.8). To characterize the change in fluorescence during plaque ablation, mechanical plaque ablation with a cold microtome was performed on 16 atherosclerotic aortic specimens. Fluorescence spectra were recorded serially after each 100 microns of plaque ablation; recordings revealed a change in fluorescence spectra from atherosclerotic to a normal pattern. With an LIF ratio of 1.8 to signal termination of plaque ablation, 15 of the atherosclerotic plaques had a residual plaque thickness less than 200 microns; one specimen had a residual plaque thickness of 300 microns. No specimen demonstrated ablation of the media. There was a statistically significant correlation between LIF ratio and plaque thickness (r = .73, P less than .001), but considerable variation in LIF ratio existed at each thickness. Therefore, laser-induced fluorescence spectroscopy is capable of discriminating atherosclerotic from normal aorta and of signaling completion of plaque ablation.