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Biomedical subjects

M S Feld

Publications and source records attributed to M S Feld.

At least 55 records · Page 3Linked to original sources
PubMed1993

Biochemical analysis and mapping of atherosclerotic human artery using FT-IR microspectroscopy.

We report the application of FT-IR microspectroscopy for in situ spectroscopic characterization of molecular constituents of human atherosclerotic lesions. Since water content in tissue affects conformation-sensitive protein vibrational bands, tissue specimens were examined under moist conditions. In all measurements, vibrational bands from water were found to dominate the spectrum. By removing these water contributions, well resolved bands due to tissue components were readily observed. Utilizing the high sensitivity and good spatial resolution of IR microspectroscopy, spectra from a sample volume of 40 x 40 x 4 microns3 were collected using unstained cryostat sections mounted on a BaF2 flat in neutral isotonic saline. Microstructures were confirmed histologically by light microscopy in stained serial sections. In the spectrum of normal intima, major bands due to amide I (1656 cm-1), amide II (1556 cm-1), and CH bending (1457 cm-1) vibrations of the proteins collagen and elastin were observed. In the spectrum of the intima of noncalcified atherosclerotic plaque, major bands due to both proteins and lipids were observed. The lipid bands at 1734, 1468, 1171 and 1058 cm-1 were assigned to the C = O (ester) stretch, CH2 bend, C--O (ester) stretch and C--O stretch, respectively. At a more detailed level, bands specific to free cholesterol, and cholesterol esters were identified. A plot of the integrated intensity ratio of these bands to the protein amide II mode versus depth from the luminal surface confirmed a heterogeneous distribution of these constituents in the atheromatous core. In the spectra of calcified atherosclerotic plaque, bands were attributed to three types of biochemical microstructures: proteins (1657, 1555, 1243 cm-1), lipids (1735, 1466, 1170, 1085, 1055 cm-1) and calcium minerals such as hydroxyapatite (1094, 1040, 962 cm-1), and carbonated apatite (1463, 1412, 872 cm-1). The results demonstrate that IR microspectroscopy can be used for in situ characterization of molecular constituents in human unstained arterial sections. The molecular information obtained from these studies could be important in understanding the pathogenesis of atherosclerosis.

Aorta↗
PubMed1992

Quantitative histochemical analysis of human artery using Raman spectroscopy.

We have developed a method for using near infrared Raman spectroscopy to quantitatively analyze the histochemical composition of human artery. The main contributors to bands observed in the Raman spectra of normal and atherosclerotic aorta are the proteins collagen and elastin, cholesterol lipids, and calcium hydroxyapatite. The Raman scattering cross-sections of different bands for these components have been determined in order to understand their relative contributions to the Raman spectra of biological tissue. The Raman signal is observed to behave linearly with the concentration of the components, even in a highly scattering medium such as a powder. Using these data, we have developed a linear model that can be used to extract the quantitative contribution of an individual component to the spectrum of a mixture. The model has been applied to several mixtures of known composition of tissue constituents in order to evaluate its precision and accuracy. The calculated fit coefficients from the spectra are in agreement with the measured values within experimental uncertainties. The spectra of different types of atherosclerotic aorta have also been modeled, and we have extracted quantitative information regarding the relative concentration of biological constituents in atherosclerotic aorta.

Arteries↗
PubMed1992

In situ optical histochemistry of human artery using near infrared Fourier transform Raman spectroscopy.

In this paper we demonstrate that near infrared Fourier transform Raman spectroscopy provides unprecedented biochemical information about the extent of atherosclerosis in human aorta. In particular, elastin, collagen, cholesterol, cholesterol esters, lipids, carotenoids, and calcium apatite deposits all can be discerned by using this technique, permitting study of each stage in the disease process. Additionally, these moieties can be detected over 1.5 mm below the irradiated surface of the tissue, possibly allowing extraction of three-dimensional information about the histology of atherosclerotic plaques. We propose that this technique may be utilized for in situ optical histochemical analysis of atherosclerosis in particular and human disease in general.

Aorta↗
PubMed1991

Wavelength dependence of pulsed laser ablation of calcified tissue.

Pulsed laser ablation of calcified biological tissue was studied at several wavelengths in the near-ultraviolet, visible, near- and mid-infrared regions of the spectrum. The primary tissue model was bovine shank bone, while human arterial calcified plaque and normal human artery wall were also studied at selected wavelengths for comparison. Laser irradiances were on the order of MW/mm2, fluences ranged up to 1000 mJ/mm2, and repetition rates varied between 0.3-10 Hz. Spot sizes on the tissue surface ranged from 150 to 850 microns. Laser craters made with wavelengths between lambda = 295 nm and lambda = 375 nm and in the lambda = 3 microns region exhibited the highest quality ablation with clean, sharp cuts following closely the spatial contour of the incident beam. Craters drilled with visible wavelengths between lambda = 450 nm and lambda = 590 nm were generally larger than the incident laser beam spot, irregular in shape and often surrounded by large flakes of tissue debris. Ablation fluence thresholds increased with wavelength through the visible wavelengths and into the mid-infrared, but dropped to their lowest values near lambda = 3 microns. Fluence thresholds obtained with the tissue under a 1 mm depth of saline were approximately twice air thresholds. Ablation yields also varied with wavelength, probably due to increased scattering in the visible region, and were the same under saline as in air.

Absorption↗
PubMed1991

476 nm excited laser-induced fluorescence spectroscopy of human coronary arteries: applications in cardiology.

We have shown that normal coronary arteries and noncalcified and calcified atherosclerotic plaque can be differentiated on the basis of the 476 nm excited fluorescence spectra, providing the basis of a spectroscopic guidance system for coronary artery laser angiosurgery. This discrimination is based on extraction of parameters from tissue fluorescence spectra, which are proportional to the tissue concentrations of structural proteins (collagen and elastin) and ceroid via a model of tissue fluorescence. We use these parameters to calculate the likelihood that an area of interest in a coronary artery is normal, noncalcified, or calcified plaque. This method of diagnosing atherosclerosis provides information about the histochemical composition of atherosclerotic lesions and is thus fundamentally different from the diagnostic methods currently used. It may ultimately have bearing on a number of pertinent clinical problems. We have discussed applications to studying initiating factors in formation and progression of plaque, healing after interventional treatments, and the likelihood of restenosis after PTCA.

Algorithms↗
PubMed1991

Characterization of the fluorescent morphological structures in human arterial wall using ultraviolet-excited microspectrofluorimetry.

In this study, the fluorescent morphological structures in normal coronary artery, normal aorta, and atherosclerotic aorta were histochemically identified and spectroscopically characterized in situ using ultraviolet-excited microspectrofluorimetry. Excitation wavelengths of 290 nm and 310/312 nm were employed to observe two distinct fluorescence bands, with peak emission wavelengths near 335 nm and 380 nm, respectively. Emission of the short wavelength 335 nm band, previously assigned to tryptophan residues in tryptophan-containing proteins, was observed from all the morphological structures in the vessel walls and was isolated in groups of smooth muscle cells in aorta and coronary artery media. The long wavelength 380 nm band was assigned to distinct fluorophores associated with the structural proteins collagen and elastin and was observed in collagen fibers and elastic fibers, respectively. The corresponding morphological structures in normal aorta, normal coronary artery, and atherosclerotic aorta exhibited similar fluorescence lineshapes. In atherosclerotic plaque, a distinct fluorescence band, peaking near 370 nm, was observed in the emission from both ceroid granules and necrotic core. Using a simple, quantitative model, differing contributions of collagen, elastin, and tryptophan-containing protein fluorescence were shown to account for over 95% of the emission from the intima, media, and adventitia layers of non-necrotic aorta and coronary artery.

Aorta↗
PubMed1991

Spectroscopic diagnosis of colonic dysplasia.

We have developed a method for defining diagnostic algorithms for pathologic conditions based on fluorescence spectroscopy. We apply this method to human colon tissue and show that fluorescence can be used to diagnose the presence or absence of colonic adenoma. This method uses fluorescence excitation-emission matrices (EEM) to identify optimal excitation regions for obtaining fluorescence emission spectra which can be used to differentiate normal and pathologic tissues. In the case of normal and adenomatous colon tissue, these were found to be: 330, 370, and 430 nm +/- 10 nm. At these excitation wavelengths, emission wavelengths for use in diagnostic algorithms are identified from average difference and ratio of the spectra from normal and pathologic tissues. In colon tissue, at 370 nm excitation, 404, 480, and 680 nm were found to be useful emission wavelengths for diagnosing the presence of adenoma in vitro. The basis of colon tissue autofluorescence was investigated using EEM of pure molecules and relevant excitation-emission maxima in the literature.

Adenoma↗
PubMed1990

Laser induced fluorescence spectroscopy of normal and atherosclerotic human aorta using 306-310 nm excitation.

Ultraviolet excited laser induced fluorescence (LIF) was studied in normal and atherosclerotic human arterial wall in vitro. Using excitation wavelengths from 306 to 310 nm, two distinct emission bands were observed in the LIF of both normal and pathologic aorta: a short wavelength band, peaking at 340 nm emission, which was attributed to tryptophan; and a long wavelength band, peaking at 380 nm emission, which was assigned to a combination of collagen and elastin. The intensity of the short wavelength band was quite sensitive to the choice of excitation wavelength, while the long wavelength band was not, so that the relative contributions of the bands could be controlled by the precise choice of excitation wavelength. A valley in the spectra at 418 nm was attributed to fluorescence reabsorption by oxy-hemoglobin. By using 308 nm excitation to observe emission simultaneously from both the short and long wavelength bands, normal and atherosclerotic aorta were spectrally distinct. Two LIF emission intensity ratios were defined to characterize both the relative tryptophan fluorescence content as well as the ratio of elastin to collagen fluorescence in each spectrum. The differences in these two emission ratios among the various histologic tissue types correlated qualitatively with the histologic and biochemical compositions of these tissues. By combining these parameters in a binary classification scheme, normal and atherosclerotic aorta were correctly distinguished in 56 of 60 total cases. Furthermore, atherosclerotic plaques, atheromatous plaques, and exposed calcifications could be classified individually with sensitivities/predictive values of 90%/90%, 100%/75%, and 82%/82%, respectively.

Aorta↗
PubMed1990

Comparison of oral erythromycin ethylsuccinate and ciprofloxacin in the treatment of acute respiratory tract infections.

A total of 619 patients with acute upper or lower respiratory tract infection were randomised to receive either erythromycin ethylsuccinate tablets at a dose of 1 g twice daily, or ciprofloxacin tablets 500 mg twice daily in a single-blind, multicentre study. The efficacy of each antibacterial was similar, with close to 90% of patients on each treatment being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side-effects, being similar in overall incidence for both agents. Nausea, vomiting, dizziness and headache occurred more frequently in the ciprofloxacin group, while abdominal pain and diarrhoea occurred more frequently in the erythromycin ethylsuccinate group. In each group, the number of patients failing to complete treatment was similar and the main reasons cited for discontinuation were gastrointestinal symptoms. This study indicates that both erythromycin ethylsuccinate and ciprofloxacin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.

Adolescent↗
PubMed1989

Alteration of spectral characteristics of human artery wall caused by 476-nm laser irradiation.

Fluorescence spectroscopy is a promising new technique for discrimination of normal and atherosclerotic arterial tissues. It has been suggested that this technique be used as a guidance system for laser angiosurgery catheters; however, irradiation by 476-nm light can change the spectroscopic properties of arterial tissue. We present studies that establish intensity levels and exposure times at which alterations in tissue spectral properties are minimal. We also investigate the nature of spectral alterations following exposure of normal human aorta to high intensities of 476-nm laser light. Changes in laser-induced fluorescence (LIF) are characterized by two prominent features: the peak fluorescence intensity decreases permanently, and the fluorescence lineshape changes in a largely reversible way. We relate these changes to alterations in individual tissue chromophores: permanent changes in absolute fluorescence intensity are due to irreversible changes in tissue fluorophores, reversible changes in fluorescence lineshape are due alterations in tissue absorbers. A simple kinetic model is used to describe the decrease in absolute fluorescence intensity.

Aorta↗
PubMed1989

Spectral diagnosis of atherosclerosis using an optical fiber laser catheter.

This communication demonstrates that fluorescence spectra of human aorta with good S/N ratios can be collected using an optical fiber laser catheter. The performance of this catheter is compared to a non-fiber optic collection system with an equivalent delivery/collection geometry. For a given sample, fluorescence lineshapes obtained using the two systems are identical; differences in peak fluorescence intensity are related to the different collection efficiencies of the two systems. It is shown that the fluorescence lineshape of arterial tissue depends on the delivery/collection geometry of the detection system, and that this is due to the interaction of absorption and fluorescence within the artery wall. This effect is investigated systematically using a specially designed collection system. Results are analyzed qualitatively using a simple, one-dimensional model of tissue fluorescence. With this analysis, we present design requirements for a collection system in which such geometric effects are eliminated, and show that our optical fiber laser catheter satisfies these requirements.

Aortic Diseases↗
PubMed1989

Argon ion laser-excited autofluorescence in normal and atherosclerotic aorta and coronary arteries: morphologic studies.

Argon ion laser-excited autofluorescence was studied in unstained frozen sections of 47 normal and atherosclerotic human aortas and coronary arteries by means of a bright-field microscope modified for fluorescence microscopy with 476 nm argon ion laser epillumination, and compared to morphology in serial sections stained with H & E, Movat pentachrome, and oil red O. Normal artery autofluorescence correlated morphologically with the structural protein fibers elastin and collagen in the intima, media, and adventitia. Atherosclerotic plaque autofluorescence correlated morphologically with lipid or calcified deposits in the atheroma core. The autofluorescence of these deposits differed from that of elastin and collagen in distribution, intensity, and color, and increased with the severity of the plaque. We conclude that argon ion laser-excited autofluorescence in normal and atherosclerotic arteries correlates with morphology and has diagnostic potential in laser angiosurgery.

Adult↗
PubMed1989

A one-layer model of laser-induced fluorescence for diagnosis of disease in human tissue: applications to atherosclerosis.

This paper describes a general model of tissue fluorescence which can be used both to: 1) determine chemical and physical properties of the tissue, and 2) design an optimal algorithm for clinical diagnosis of tissue composition. This model is based on a picture of tissue as a single, optically thick layer, in which fluorophores and absorbing species are homogeneously distributed. As a specific example, the model is applied to the laser induced fluorescence (LIF) of normal and atherosclerotic human aorta using 476 nm excitation. Methods for determining the relevant attenuation and fluorescence lineshapes are detailed, and these lineshapes are used to apply the model to data from 148 samples. The model parameters are related to the concentrations of the major arterial chromophores: structural proteins, hemoglobin and ceroid. In addition, the model parameters are used to derive diagnostic algorithms for the presence of atherosclerosis. Utilizing a binary classification scheme, the presence or absence of pathology was determined correctly in 88 percent of cases.

Algorithms↗
PubMed1988

Remote biomedical spectroscopic imaging of human artery wall.

We discuss a general technique, laser spectroscopic imaging (LSI), remote acquisition of spectroscopic images of biological tissues and tissue conditions. The technique employs laser-induced spectroscopic signals, collected and transmitted via an array of optical fibers, to produce discrete pixels of information from which a map or image of a desired tissue characteristic is constructed. We describe a prototype LSI catheter that produces spectral images of the interior of human arteries for diagnosis of atherosclerosis. The diagnostic is based on the fact that normal artery wall and atherosclerotic plaque exhibit distinct fluorescence spectra in the 500-650 nm range when excited by 476-nm laser light; the fluorescence from blood is minimal. The catheter is composed of 19 optical fibers enclosed in a transparent, protective shield. Argon ion laser radiation is used for excitation, and an optical multichannel spectral analyzer is used for detection. Sequential sampling is used to minimize crosstalk among fibers and reduce blurring of the image. Computer-processed 19-pixel spectroscopic images are produced of fresh cadaver artery in vitro. Regions of normal tissue, plaque, and blood are identified, and the diagnoses are confirmed histologically and by direct spatial correlation. The results demonstrate the concept of using this laser catheter system for real-time imaging.

Arteriosclerosis↗
PubMed1988

Effects of varying argon ion laser intensity and exposure time on the ablation of atherosclerotic plaque.

Using continuous wave (CW) argon ion laser light, a total of 253 laser exposures of varying power (1.5, 3, 5, 8 or 10 W) and duration (20-1,333 ms) were delivered to four segments of human atheromatous aorta obtained at autopsy. Exposure conditions were controlled by using an optically shielded laser catheter that provided a 500 micron spot of light of known power. Two thresholds for consistently reproducible ablation could be defined-an intensity threshold at 25.5 W/mm2 and a fluence threshold at 3.2 J/mm2. Above threshold, a fluence of 5.1 J/mm2 was found to produce the most efficient ablation, ie, removed the greatest volume (mm3) per energy delivered (J) compared to other fluence levels employed (p less than 0.0001). Between aortic segments, however, considerable variability in efficiency (mm3/J) was observed, possibly owing to different optical properties and/or plaque composition. Low-intensity laser radiation produced inconsistent ablation and extensive coagulation effects to surrounding tissue. When a fluence of 5.1 J/mm2 was constructed with a high-intensity laser beam and a short exposure time, consistent and efficient tissue removal resulted without histologic evidence of coagulation necrosis.

Angioplasty, Balloon↗
PubMed1988

Removal of surgically induced fibrous arterial plaques by argon ion laser angiosurgery using a multifiber delivery system. An experimental study in the dog.

Removal of intravascular atherosclerotic obstructions by laser irradiation has gained the attention of many investigators, but has proven to be considerably more difficult to accomplish than initially envisioned. We tested, in an animal model, an argon ion laser delivery system that permits control of (1) laser power, (2) exposure time, and (3) laser beam spot size. The study was conducted on surgically, induced focal fibrous plaques in the carotid arteries of nine dogs. Plaque removal, vessel patency, and healing were evaluated angiographically and by light and electron microscopy at intervals up to 60 days after treatment. Results showed that intravascular obstructions could be removed, healing occurred, and vessels remained patent for up to 60 days.

Animals↗