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Biomedical subjects

I Itzkan

Publications and source records attributed to I Itzkan.

16 recordsLinked to original sources

In vivo identification of colonic dysplasia using fluorescence endoscopic imaging.

BACKGROUND: Previous in vitro studies showed that autofluorescence images of colonic mucosa collected endoscopically can be used to detect dysplasia with high sensitivity. This method is extended to the collection of fluorescence images of adenomatous polyps in vivo. METHODS: Fluorescence images were collected during colonoscopy in 30 patients. A total of 12 adenomatous and 6 hyperplastic polyps were identified. A fiberoptic excitation probe, located in the instrument channel of the colonoscope, delivered 300 mW of near-ultraviolet light at lambdaex = 351 and 364 nm. Mucosal fluorescence in the spectral bandwidth between 400 and 700 nm was imaged, processed, and displayed with various likelihoods of associated dysplasia. RESULTS: Adenomatous polyps exhibited decreased fluorescence intensity compared with adjacent mucosa with normal appearance. With the fluorescence threshold set to 80% of the average intensity of normal mucosa, a sensitivity of 83% for dysplasia identification was achieved. All hyperplastic polyps were correctly identified as being non-dysplastic. Optimal identification of dysplastic regions was obtained with the colonoscope oriented at a near-normal angle of incidence to the polyps. At higher angles of incidence, artifacts caused by illumination shadows were introduced. CONCLUSIONS: The dysplasia associated with adenomatous polyps can be identified in vivo by fluorescence imaging with high sensitivity, thus demonstrating the potential to guide endoscopic procurement of biopsy specimens.

Adenomatous Polyps

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

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

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

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

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

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

In vivo spectrophotometric evaluation of normal, lesional, and laser-treated skin in patients with port-wine stains.

The influence of patient age and argon laser therapy on port-wine stains (PWS) was studied quantitatively in 16 patients aged 15-64 years using a spectrophotometer and computer graphics/statistics program. Normalized reflectance curves revealed a 10-20% decrease with age in the reflectance of normal skin from 400 nm to 650 nm, with an even more pronounced reflectance decrease in the region of peak deoxyhemoglobin absorption at approximately 555 nm. In each patient, PWS reflectance was less than that in the normal skin, as expected, and the average discrepancy increased with age from approximately 25% to 50%, with further reduction at 555 nm. The data suggest that with advancing age, both normal skin and PWS have a greater total hemoglobin content and an increased proportion of deoxyhemoglobin, consistent with increasing vascular dilation and tortuosity; and that the age-associated changes in PWS are an exaggeration of those in normal skin. Laser-treated PWS in both young and old patients had reflectance curves indistinguishable from those of untreated PWS in young patients. This implies, contrary to published clinical impressions, that in the absence of scarring the results of argon laser therapy are the same in young and old patients, but that only older patients experience a significant color shift in the lesion.

Adolescent

Laser therapy. Basic concepts and nomenclature.

Laser therapy has been demonstrated to be effective in treating many types of cutaneous vascular and pigmented lesions. Clinical and investigative studies on lasers are being published with increasing frequency, but is difficult to interpret and compare results because of lack of use of appropriate nomenclature regarding laser energy. We suggest that scientific communication in this expanding field will be improved if all future studies state: (1) irradiance (laser flux density) at the irradiated surface in watts/cm2, (2) laser beam cross-sectional area and shape at the irradiated surface, (3) laser pulse duration or exposure time in seconds, (4) pulse repetition rate (pulsed lasers) in pulses per second, (5) treatment time segments and intervals between treatment times, (6) total treated skin area in cm2, (7) total number of applied laser pulses or exposures, and (8) the type of laser used and its spectral distribution.

Humans