Detection of preinvasive cancer cells.
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Carcinoma↗
Biomedical subjects
I Itzkan
Publications and source records attributed to I Itzkan.
Prospects for in vivo Raman spectroscopy.
Raman spectroscopy is a potentially important clinical tool for real-time diagnosis of disease and in situ evaluation of living tissue. The purpose of this article is to review the biological and physical basis of Raman spectroscopy of tissue, to assess the current status of the field and to explore future directions. The principles of Raman spectroscopy and the molecular level information it provides are explained. An overview of the evolution of Raman spectroscopic techniques in biology and medicine, from early investigations using visible laser excitation to present-day technology based on near-infrared laser excitation and charge-coupled device array detection, is presented. State-of-the-art Raman spectrometer systems for research laboratory and clinical settings are described. Modern methods of multivariate spectral analysis for extracting diagnostic, chemical and morphological information are reviewed. Several in-depth applications are presented to illustrate the methods of collecting, processing and analysing data, as well as the range of medical applications under study. Finally, the issues to be addressed in implementing Raman spectroscopy in various clinical applications, as well as some long-term directions for future study, are discussed.
Alzheimer Disease↗
Physical properties of hydrated tissue determined by surface interferometry of laser-induced thermoelastic deformation.
Knee meniscus is a hydrated tissue; it is a fibrocartilage of the knee joint composed primarily of water. We present results of interferometric surface monitoring by which we measure physical properties of human knee meniscal cartilage. The physical response of biological tissue to a short laser pulse is primarily thermomechanical. When the pulse is shorter than characteristic times (thermal diffusion time and acoustic relaxation time) stresses build and propagate as acoustic waves in the tissue. The tissue responds to the laser-induced stress by thermoelastic expansion. Solving the thermoelastic wave equation numerically predicts the correct laser-induced expansion. By comparing theory with experimental data, we can obtain the longitudinal speed of sound, the effective optical penetration depth and the Grüneisen coefficient. This study yields information about the laser tissue interaction and determines properties of the meniscus samples that could be used as diagnostic parameters.
Elasticity↗
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↗
Near-infrared fluorescence spectroscopy detects Alzheimer's disease in vitro.
The purpose of this study was to investigate whether near-infrared (NIR) fluorescence spectroscopy could be used to detect Alzheimer's disease (AD) by brain tissue autofluorescence. Unfixed temporal cortex specimens from AD cases and age-matched, non-AD controls were frozen at autopsy and then thawed just prior to spectral measurement. Spectra of intrinsic tissue fluorescence induced by 647 nm light were recorded from 650 to 850 nm. We used principal component analysis of the tissue spectra from 17 AD cases and 5 non-AD control cases in a calibration study to establish a diagnostic algorithm. Retrospectively applied to the calibration set, the algorithm correctly classified 23 of 24 specimens. In a prospective study of 19 specimens from 5 AD brains and 2 non-AD control brains, 3 of the 4 control specimens and all AD specimens were correctly diagnosed. Both the excitation light used and the measured brain tissue autofluorescence are at NIR wavelengths that can propagate through skull and overlying tissue. Therefore, our results demonstrate an optical spectroscopic technique that carries direct molecular level information about disease. This is the first step toward a clinical tool that has the potential to be applied to the noninvasive diagnosis of AD in living patients.
Alzheimer Disease↗
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↗
Population pumping of excited vibrational states by spontaneous surface-enhanced Raman scattering.
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Journal Article↗
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↗
Time-dependent photon migration using path integrals.
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Journal Article↗
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↗
Photon migration in turbid media using path integrals.
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Journal Article↗
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↗