Search PubMed⌕ Search

Biomedical subjects

M S Feld

Publications and source records attributed to M S Feld.

At least 37 records · Page 2Linked to original sources

An enhanced algorithm for linear multivariate calibration.

We present a new method of linear multivariate calibration that can generate better prediction results than those obtained by partial least squares (PLS). This is accomplished by incorporating the spectrum of the desired species into the calibration procedure. The method combines the advantages of different standard methods and is therefore called hybrid linear analysis (HLA). In side-by-side tests using both simulated and experimental data, HLA produced lower prediction errors than PLS in all instances. We recommend HLA over PLS in situations where the spectrum of the desired species is available.

Algorithms↗

Biochemical composition of human peripheral arteries examined with near-infrared Raman spectroscopy.

PURPOSE: Near-infrared Raman spectroscopy provides an important new means of analyzing the chemical composition of the arterial wall. The objective of this study was to show that Raman spectroscopy can be used to evaluate the lipid and calcium salt contents of human peripheral arteries. The results extend a recently developed Raman-based method for analyzing the chemical composition of coronary arteries. METHODS AND RESULTS: We studied 167 segments of carotid and femoral artery wall in various pathologic states. The Raman spectra from these samples was accurately modeled. The resulting chemical concentrations were compared with the amounts of cholesterol and calcium mineral determined at histologic evaluation by an experienced cardiovascular pathologist. Strong correlations between spectroscopic measurements and morphologic findings were demonstrated and validated the applicability of the method to peripheral arteries. CONCLUSIONS: Raman spectroscopy can provide reliable histochemical information about peripheral and coronary arteries. Such information may help identify rupture-prone plaques before the onset of symptoms and allow aggressive and directed intervention. Accurate knowledge of the chemical composition of a lesion may be useful in selecting the most appropriate treatment.

Arteriosclerosis↗

Diagnosis of head and neck precancerous lesions in an animal model using fluorescence spectroscopy.

Laser-induced fluorescence (LIF) of tissues depends on their biochemical and histomorphologic characteristics. LIF spectroscopic properties of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced precancerous and early cancerous lesions in a hamster buccal pouch mucosa model were studied. Fluorescence spectra from neoplastic lesions showed a characteristic fluorescence peak in the red region of the visible spectrum centered between 630 and 640 nm when excited with 410-nm light. Using this as a diagnostic criterion, 45 of 49 lesions studied were correctly diagnosed, including early dysplastic lesions. Follow-up study of four dysplastic lesions over 2 weeks revealed an increase in red fluorescence intensity. The findings of these experiments suggest that LIF spectroscopy may be a valuable noninvasive technique not only for early diagnosis of head and neck cancer, but also to probe a possible biochemical surrogate biomarker in the follow-up of suspected lesions.

9,10-Dimethyl-1,2-benzanthracene↗

Raman spectroscopy and fluorescence photon migration for breast cancer diagnosis and imaging.

We are developing optical methods based on near infrared Raman spectroscopy and fluorescence photon migration for diagnosis and localization of breast cancer. We demonstrate the ability of Raman spectroscopy to classify accurately normal, benign and malignant breast tissues, an important step in developing Raman spectroscopic needle probes as a tool for improving the accuracy of needle biopsy. We also show that photon migration imaging can be used to localize accurately small fluorescent objects imbedded in a thick turbid medium with realistic optical properties, thus demonstrating the potential of this technique for optical imaging.

Breast Neoplasms↗

Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms.

We present a multichannel tomographic technique to detect fluorescent objects embedded in thick (6.4 cm) tissue-like turbid media using early-arriving photons. The experiments use picosecond laser pulses and a streak camera with single photon counting capability to provide short time resolution and high signal-to-noise ratio. The tomographic algorithm is based on the Laplace transform of an analytical diffusion approximation of the photon migration process and provides excellent agreement between the actual positions of the fluorescent objects and the experimental estimates. Submillimeter localization accuracy and 4- to 5-mm resolution are demonstrated. Moreover, objects can be accurately localized when fluorescence background is present. The results show the feasibility of using early-arriving photons to image fluorescent objects embedded in a turbid medium and its potential in clinical applications such as breast tumor detection.

Algorithms↗

Determination of human coronary artery composition by Raman spectroscopy.

BACKGROUND: We present a method for in situ chemical analysis of human coronary artery using near-infrared Raman spectroscopy. It is rapid and accurate and does not require tissue removal; small volumes, approximately 1 mm3, can be sampled. This methodology is likely to be useful as a tool for intravascular diagnosis of artery disease. METHODS AND RESULTS: Human coronary artery segments were obtained from nine explanted recipient hearts within 1 hour of heart transplantation. Minces from one or more segments were obtained through grinding in a mortar and pestle containing liquid nitrogen. Artery segments and minces were excited with 830 nm near-infrared light, and Raman spectra were collected with a specially designed spectrometer. A model was developed to analyze the spectra and quantify the amounts of cholesterol, cholesterol esters, triglycerides and phospholipids, and calcium salts present. The model provided excellent fits to spectra from the artery segments, indicating its applicability to intact tissue. In addition, the minces were assayed chemically for lipid and calcium salt content, and the results were compared. The relative weights obtained using the Raman technique agreed with those of the standard assays within a few percentage points. CONCLUSIONS: The chemical composition of coronary artery can be quantified accurately with Raman spectroscopy. This opens the possibility of using histochemical analysis to predict acute events such as plaque rupture, to follow the progression of disease, and to select appropriate therapeutic interventions.

Calcium↗

Autofluorescence characteristics of oral mucosa.

BACKGROUND: The fluorescence characteristics of tissues depend upon their biochemical composition and histomorphological architecture, both of which undergo a change during malignant transformation. These changes are detectable as an alteration in the fluorescence spectral profile of the tissues. METHODS: Biopsy specimens from clinically suspicious lesions and normal-appearing oral mucosa were obtained from patients. Fluorescence spectroscopic measurements were obtained to study the differences between normal and dysplastic tissues and to determine the most appropriate excitation wavelength(s) for exploiting these differences. RESULTS: Fluorescence spectra from a total of 12 histologically normal (healthy mucosa or benign lesions) and ten abnormal (dysplastic or malignant) tissue samples were compared. Significant spectral differences were seen between the two groups. These differences were most marked at the excitation wavelength of 410 nm. Using this wavelength, fluorescence correctly diagnosed 20 of 22 samples studied. CONCLUSIONS: This technique accurately differentiates normal from abnormal tissues in vitro and has the potential applications for in vivo use as a noninvasive diagnostic tool.

Biopsy↗

Feasibility of measuring blood glucose concentration by near-infrared Raman spectroscopy.

We report the determinations of glucose concentrations in human whole blood samples made using near-infrared Raman spectroscopy. Raman spectra of blood samples with above-physiological levels of glucose were acquired for 5 min through the wall of a cuvette via fiber optics. Partial least squares analysis was used to predict glucose concentrations in the samples. A root mean squared prediction error of 3.6 mM glucose was achieved with a correlation coefficient of 0.99 between reference and predicted values. This result is the first step in evaluating the potential of near-infrared Raman spectroscopy to perform blood glucose measurement with clinical accuracy. The technique is capable of measuring the concentration of other Raman-active blood constituents; as an example, bicarbonate was also measured. The method could eventually be useful for direct measurement of tissue analytes.

Blood Chemical Analysis↗

Photon migration of near-diffusive photons in turbid media: a Lagrangian-based approach.

We show that light transport in a turbid medium can be described by a path integral with a quasi-particle Lagrangian. The most probable trajectory over which photons can be found can be obtained from this Lagrangian. This approach extends the diffusion approximation to the near-diffusive regime, in which photons travel only a few transport mean free paths.

Diffusion↗

Early diagnosis of upper aerodigestive tract cancer by autofluorescence.

OBJECTIVE: To explore the potential of autofluorescence spectroscopy as a tool for early detection of upper aerodigestive tract cancer. DESIGN: Autofluorescence spectral characteristics of 19 untreated oral and oropharyngeal lesions in 13 patients were studied with excitation wavelengths of 370 and 410 nm generated by a nitrogen pumped dye laser. Ten healthy volunteers were recruited to characterize the fluorescence spectra of normal mucosa at different oral sites and to study individual variations. Fluorescence intensity and line shape of the spectra from lesions were compared with the same parameters from the contralateral control site in the same individual. SETTING: Otolaryngology Research Center, Department of Otolaryngology-Head and Neck Surgery, New England Medical Center, Boston, Mass. RESULTS: The ratio of peak fluorescence intensities of the neoplastic lesions to contralateral normal control mucosa were consistently different compared with these ratios in benign lesions or normal mucosa. These differences were seen in 2 distinct regions of the fluorescence spectrum with both of the excitation wavelengths, but were more obvious with the excitation wavelength of 410 nm. Using these differences, we were able to correctly diagnose 17 of the 19 lesions studied, with 2 false-positive results. CONCLUSIONS: Neoplastic oral mucosa shows consistent differences in autofluorescence spectral intensity and line shape when compared with the normal mucosa in the same individual. These early results show that fluorescence spectroscopy may represent a useful technique for noninvasive early diagnosis of cancer of the upper aerodigestive tract.

Adult↗

Detection of dysplasia at colonoscopy using laser-induced fluorescence: a blinded study.

BACKGROUND: Laser-induced fluorescence spectroscopy has the potential to detect colonic dysplasia in vivo. However, previous studies have limited their analyses to multivariate regression techniques and unblinded retrospective evaluation. The purpose of this study was to develop a probability-based algorithm to detect colonic dysplasia using laser-induced fluorescence spectroscopy and to evaluate it in a blinded manner. METHODS: Fluorescence spectra were collected from normal mucosa and colonic polyps during colonoscopy using 370 nm excitation. Tissue was classified as normal, hyperplastic, or adenomatous by histologic examination. Preliminary data was used to devise an algorithm to differentiate tissue type based on probability distributions of the fluorescence intensity at 460 nm and the ratio of the intensity at 680 nm to that at 600 nm. The algorithm was then tested in a blinded fashion. RESULTS: The algorithm correctly determined the tissue type in 88% of cases, equal to the agreement of independent pathologists. Sensitivity, specificity, and positive predictive value for the detection of dysplasia was 90%, 95%, and 90%, respectively. CONCLUSIONS: Dysplasia was detected in vivo using fluorescence spectroscopy and a probability-based algorithm. This method may form the basis for a new surveillance technique for patients with increased risk for dysplastic transformation.

Adenomatous Polyps↗

Fluorescence endoscopic imaging of human colonic adenomas.

BACKGROUND & AIMS: Endoscopic screening for sporadic colorectal cancer relies in part on the detection of adenomatous polyps. Nonpolypoid adenomas or flat dysplasia may go unrecognized by conventional endoscopy. This study attempted to develop and test a novel endoscopic method for detecting polypoid and nonpolypoid colonic adenomas. METHODS: Colectomy specimens from 3 patients with familial adenomatous polyposis containing polypoid and nonpolypoid adenomas were illuminated with excitation light at 351 and 364 nm. Endoscopic images of the net tissue fluorescence emitted were collected over the spectral bandwidth from 400 to 700 nm. Each raw image was corrected for differences in distance and instrument light collection efficiency by normalizing to a spatially averaged image. Intensity thresholding was then used to identity regions of diseased mucosa. RESULTS: The average fluorescence intensity from normal mucosa was found to be greater than that from adenomas by a factor of 2.2 +/- 0.6. The sensitivity and specificity for detecting a region of dysplasia varied with the threshold value selected. At a threshold of 75% of the average normal intensity, a sensitivity of 90% and a specificity of 92% were achieved. CONCLUSIONS: Fluorescence images of colonic mucosa can be collected endoscopically, and dysplasia can be detected and localized with high sensitivity and specificity. These results show the potential of this technique to direct endoscopic biopsy.

Adenoma↗

Morphological model of human colon tissue fluorescence.

Fluorescence spectroscopy of tissue is a promising technique for early detection of precancerous changes in the human body. Investigation of the microscopic origin of the clinically observed tissue fluorescence can provide valuable information about the tissue's histology. The objective of this study was the development of a morphological model of colon tissue fluorescence which connects the clinically observed spectra with their underlying microscopic origins. Clinical colon tissue fluorescence which connects the clinically observed spectra with their underlying microscopic origins. Clinical colon tissue fluorescence spectra were modeled by measuring the intrinsic fluorescence properties of colon tissue on a microscopic level and by simulating light propagation in tissue using the Monte-Carlo method. The computed spectra were in good agreement with the clinical spectra acquired during colonoscopy, and exhibited the characteristic spectral features of the in vivo collected spectra. Our analysis quantitated these spectral features in terms of the intrinsic fluorescence properties of tissue and its general histological characteristics. The fluorescence intensity difference between normal and adenoma observed in vivo was found to be due to the increased hemoglobin absorption, the reduced mucosal fluorescence intensity, and the absence of submucosal fluorescence in adenomatous polyps. The increased red fluorescence in adenoma was found to be associated with the dysplastic crypt cell fluorescence.

Absorption↗

The thermoelastic basis of short pulsed laser ablation of biological tissue.

Strong evidence that short-pulse laser ablation of biological tissues is a photomechanical process is presented. A full three-dimensional, time-dependent solution to the thermoelastic wave equation is compared to the results of experiments using an interferometric surface monitor to measure thermoelastic expansion. Agreement is excellent for calibrations performed on glass and on acrylic at low laser fluences. For cortical bone, the measurements agree well with the theoretical predictions once optical scattering is included. The theory predicts the presence of the tensile stresses necessary to rupture the tissue during photomechanical ablation. The technique is also used to monitor the ablation event both before and after material is ejected.

Animals↗

Mechanisms of meniscal tissue ablation by short pulse laser irradiation.

A new experimental technique was developed to study short-pulsed laser ablation of biologic tissues (human meniscus and bovine tibial bone), water, and acrylic. The experimental technique was based on interferometric monitoring of the motion of the tissue surface to measure its laser-induced expansion after irradiation. The thermoelastic expansion of these materials after laser irradiation under subablation threshold was examined to determine its role in the initiation of ablation. The experimentally observed surface expansion of cortical bone and acrylic was in agreement with theoretical predictions. The movement of meniscal tissue was similar to that shown by water. The latter 2 materials showed additional features consistent with the growth and collapse of cavitation bubbles. The exact role of cavitation in the irradiation of meniscal tissue by laser light remains unknown, but may represent a clinically important mode of tissue ablation and postirradiation trauma.

Animals↗

Interferometric surface monitoring of biological tissue to study inertially confined ablation.

We present results from the application of laser interferometry to the study of short-pulsed laser ablation of biological tissue. The mechanical response of tissue to laser-induced stress is examined under subthreshold conditions to determine its role in initiating the ablation process. A theoretical model is developed to relate this surface displacement to the pressure within the tissue and the mechanical properties of the tissue. In the experiment, a 7.5 ns pulse of 355 nm light was used to irradiate bovine shank bone, human meniscus, and an aqueous dye solution. Interferometric monitoring of the tissue surface was used to determine its motion after laser irradiation. The surface movement of bone was qualitatively consistent with the theoretical predictions of the model. The movement of meniscus and an aqueous dye solution showed additional features that are consistent with the growth and collapse of cavitation bubbles.

Animals↗

Laser-induced thermoelastic deformation: a three-dimensional solution and its application to the ablation of biological tissue.

Under certain conditions, laser light incident on a target material can induce an explosive removal of some material, a process called laser ablation. The photomechanical model of laser ablation asserts that this process is initiated when the laser-induced stresses exceed the strength of the material in question. Although one-dimensional calculations have shown that short pulsed lasers can create significant transient tensile stresses in target materials, the stresses last for only a few nanoseconds and the spatial location of the peak stresses is not consistent with experimental observations of material failure in biological tissues. Using the theory of elasticity, analytical expressions have been derived for the thermoelastic stresses and deformations in an axially symmetric three-dimensional solid body caused by the absorption of laser light. The full three-dimensional solution includes three stresses, radial, circumferential and shear, which are necessarily absent in the simple one-dimensional solution. These stresses have long-lived components that exist for eight orders of magnitude longer in time than the acoustic transients, an important point when the details of dynamic fracture are considered. Many important qualitative features are revealed including the spatial location of the peak stresses, which is more consistent with experimental observations of failure.

Animals↗