Mark L. Stetz

Laser-induced fluorescence spectroscopy of human colonic mucosa: Detection of adenomatous transformation

To evaluate the potential of laser-induced fluorescence spectroscopy for the detection of premalignant lesions of the gastrointestinal tract, the hypothesis that adenomatous transformation of colonic mucosa results in an alteration of laser-induced fluorescence that enables its differentiation from normal or hyperplastic tissue was tested. A fiberoptic catheter coupled to a helium-cadmium laser (325 nm) and an optical multichannel analyzer were used to obtain fluorescence spectra (350-600 nm) from 35 normal colonic specimens and 35 resected adenomatous polyps. A score based on six wavelengths was derived by stepwise multivariate linear regression analysis of the spectra. The mean score (+/- SEM) was + 0.86 +/- 0.06 for normal mucosa and -0.86 +/- 0.06 for adenomatous polyps (P less than 0.001). Spectra from an additional 34 normal specimens, 16 adenomatous polyps, and 16 hyperplastic polyps were prospectively classified with accuracies of 100%, 100%, and 94%, respectively. The mean score for hyperplastic polyps was significantly different from adenomatous (P less than 0.001) but not from normal tissue. Thus, quantitative analysis of fluorescence spectra enables the detection of adenomatous transformation in colonic mucosa.

Development and evaluation of spectral classification algorithms for fluorescence guided laser angioplasty

The feasibility of utilizing spectral information to discriminate arterial tissue type is considered. 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 aortas with an accuracy greater than 80% (range: 82-96%). Laser angioplasty systems incorporating spectral classification algorithms may therefore be capable of detection and selective ablation of atherosclerotic plaque.<<ETX>>

Neural network and conventional classifiers for fluorescence-guided laser angioplasty

The ability of the back-propagation and K-nearest-neighbors techniques to classify arterial fluorescence spectra is investigated. Both methods are competitive with other classification schemes. The best validation set accuracy on the aortic data was obtained by the 1-nearest-neighbor method (98% correct overall on the test exemplars). The 22-8-1 and 22-8-4-1 networks performed second best, misclassifying only one more exemplar, at 96%. All performances on the coronary data were much poorer. The relative performance of variations on both techniques is used to make inferences about the geometry of the classification task.<<ETX>>

In-Vivo Fluorescence Spectroscopy Of Normal And Atherosclerotic Arteries

Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal arteries in-vitro and may thus potentially guide laser angioplasty. To evaluate the feasibility of laser-induced fluorescence spectroscopy in a living blood-filled arterial system we performed fiberoptic laser-induced fluorescence spectroscopy in a rabbit model of focal femoral atherosclerosis. A laser-induced fluorescence spectroscopy score was derived from stepwise linear regression analysis of in-vitro spectra to distinguish normal aorta (score>0) from atherosclerotic femoral artery (score<0). A 400 u silica fiber, coupled to a helium cadmium laser and optical multichannel analyzer, was inserted through a 5F catheter to induce and record in-vivo fluorescence from femoral and aortoiliac arteries. Arterial spectra could be recorded in all animals (n=10: 5 occlusions, 5 stenoses). Blood spectra were of low intensity and were easily distinguished from arterial spectra. The scores (mean ± SEM) for the in-vivo spectra were -0.69 ± 0.29 for artherosclerotic femoral, and +0.54 ±. 0.15 for normal aorta (p<.01; p=NS compared to in-vitro spectra). In-vitro, a fiber tip to tissue distance <50 u was necessary for adequate arterial LIFS in blood. At larger distances low intensity blood spectra were recorded (1/20 the intensity of tissue spectra). Thus, fiberoptic laser-induced fluorescence spectroscopy can be sucessfully performed in a blood filled artery provided the fiber tip is approximated to the tissue.

TIME RESOLVED FLUORESCENCE OF NORMAL AND ATHEROSCLEROTIC ARTERIES

Picosecond time-resolved fluorescence measurements were performed on fibrous and calcified atherosclerotic plaque and normal coronary artery with 351nm picosecond excitation of a mode-locked Nd-glass laser. Double exponential decay profiles were measured. The fast component of lifetimes of fibrous plaque is different than that of normal artery or calcified plaque and can be used to discriminate fibrous plaque from normal artery.

Medical Applications of Alexandrite Laser Systems

Alexandrite laser systems have several characteristics which are necessary for laser surgical applications. The relatively long Q-switched pulsewidths allow significant amounts of energy to be transmitted through optical fibers before the onset of fiber damage. The laser output wavelength in the fundamental (720 - 800 nm) and second harmonic (360 - 400 nm) are efficiently transmitted through commercially available fused silica fibers. The alexandrite laser may therefore be the optimal choice for numerous medical applications.

Optical and mechanical parameter detection of calcified plaque for laser angioplasty

Three potential guidance mechanisms for pulsed laser angioplasty were tested for their ability to discriminate between different tissue types. Holmium:YAG laser energy (wavelength=2.1 um, 100 mJ/pulse, 12.7 J/mm2 fluence) was delivered through a 100 um fiber into normal artery, fibrous plaque, and calcified plaque, as well as saline and blood. Plasma emission, mechanical fiber recoil, and acoustic shock wave were all measured during laser irradiation of these different substances. Plasma emission was detected by a photodiode at the proximal end of the fiber. Mechanical fiber recoil was detected using a phono cartridge mechanically coupled to the fiber 60 cm from the distal end. Acoustic sound waves were detected with a hydrophone in close proximity to the target site. The probability of generating plasma emission and the relative magnitudes (1-4) of the mechanical recoil and acoustic signal are as follows: Signal Blood Normal Aorta White Plaque Calcified Plaque plasma 0% 0% 0% 99% acoustic 4 1 1 4 recoil 1 2 2.5 4 A Fourier transform of the acoustic signal showed differences between blood, normal artery or non-calcified plaque, and calcified plaque. Mechanical recoil does not provide additional information. These techniques do not differentiate normal tissue from fibrous plaque but will discriminate calcified plaque from blood, normal artery, and non-calcified plaque. These techniques are relatively easy to implement and provide potentially useful feedback to guide laser ablation. Conclusion: The presence of plasma is a good indicator of calcified plaque; when used in conjunction with the acoustic signal it could indicate whether the fiber catheter is on calcified plaque, non-calcified tissue, or in blood.

Evaluation of spectral discriminant functions for guidance of laser angioplasty

Development of a clinically acceptable laser angioplasty system has been hindered by the inability to adequately guide ablative laser radiation to atherosclerotic plaque. Low power laser-induced fluorescence spectroscopy is capable of discriminating normal and atherosclerotic arterial tissue. The purpose of this investigation was to develop and evaluate several spectral classification algorithms that would enable discrimination of atherosclerotic and normal arterial tissue by a computer controlled fluorescence guided laser angioplasty system.

Evaluation Of Spectral Discriminant Functions For Guidance Of Laser Angioplasty

Development of a clinically acceptable laser angioplasty system has been hindered by the inability to adequately guide ablative laser radiation to atherosclerotic plaque. Low power laser-induced fluorescence spectroscopy is capable of discriminating normal and atherosclerotic arterial tissue. The purpose of this investigation was to develop and evaluate several spectral classification algorithms that would enable discrimination of atherosclerotic and normal arterial tissue by a computer controlled fluorescence guided laser angioplasty system.