Biomedical subjects

Young L Kim

Publications and source records attributed to Young L Kim.

11 recordsLinked to original sources

PubMed2006

Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa.

INTRODUCTION: Our group has been interested in applying advances in biomedical optics to colorectal cancer risk stratification. Through a recent technological breakthrough, we have been able to harness information from enhanced backscattering spectroscopy, an optics phenomenon that allows quantitative, depth-selective analysis of the epithelial microscale/nanoscale architecture. In the present study, we investigated the ability of enhanced backscattering analysis of the preneoplastic mucosa to predict risk of colon carcinogenesis. METHODS: Enhanced backscattering analysis was done on intestinal mucosa at preneoplastic time points from two experimental models of colorectal cancer: the azoxymethane-treated rat and the multiple intestinal neoplasia (MIN) mouse. Data were analyzed using two previously validated spectral markers: spectral slope and principle components. We then did a pilot study on mucosal biopsies from 63 subjects undergoing screening colonoscopy. RESULTS: In the azoxymethane-treated rat, when compared with saline-treated controls, significant changes in the enhanced backscattering markers were observed as early as 2 weeks after azoxymethane treatment (before the development of aberrant crypt foci and adenomas). Enhanced backscattering markers continued to progress over time in a manner consonant with future neoplasia. These data were replicated in the preneoplastic MIN mouse mucosa. In humans, spectral slopes in the endoscopically normal cecum, midtransverse colon, and rectum were markedly reduced in patients harboring adenomas when compared with those who were neoplasia free. CONCLUSIONS: We show, for the first time, that enhanced backscattering analysis of an aliquot of uninvolved mucosa has the potential for predicting neoplastic risk throughout the colon in both experimental colorectal cancer models and humans.

Animals↗

PubMed2006

Assessment of blood supply in superficial tissue by polarization-gated elastic light-scattering spectroscopy.

We report the feasibility of monitoring both hemoglobin oxygen saturation and hemoglobin concentration in the superficial layer of tissue using polarization-gated elastic light-scattering spectroscopy. We detail our analysis technique, the experimental validation of our analysis, and the detection of an early increase in blood supply to the superficial layer of colon tissue in human patients with colonic adenomas as well as in an animal model of colon carcinogenesis. To the best of our knowledge, this study represents the first evidence that polarization gating can be used as a spectroscopic tool to quantify hemoglobin concentration as well as oxygen saturation in the uppermost tissue layer.

Animals↗

PubMed2005

Elastic backscattering spectroscopic microscopy.

The spectral properties of elastic light-scattering signals have been shown to provide a wealth of information on nanostructures and microstructures. We present elastic backscattering spectroscopic microscopy that allows simultaneous acquisition of microscopic images and backscattering spectra at each pixel. Within a single homogeneous micrometer-scale particle we observe two distinct and highly localized spectral oscillation features that arise from different optical paths: (1) surface waves (e.g., the ripple structure) and (2) a not previously reported anomalous ripple structure that is due to the interference of waves scattered from front and back surfaces at the particle's center. We also demonstrate that the spectroscopic data can provide nanoscale structural information beyond what conventional microscopy reveals.

Equipment Design↗

PubMed2005

Development of a bioengineered tissue model and its application in the investigation of the depth selectivity of polarization gating.

Understanding the propagation of polarized light in tissue is crucial for a number of biomedical optics applications. Here we report the development of a bioengineered connective tissue model fabricated by the combination of scaffolding and cross-linking techniques to study light transport in biological tissue. It demonstrates great similarity to real connective tissue in its optical properties as well as microarchitecture. Moreover, the optical properties of the model can be reproducibly controlled. As an example, we report the utilization of this model to study the effect of epithelium and the underlying connective tissue on the depth selectivity of polarization gating.

Animals↗

PubMed2005

Depth-resolved low-coherence enhanced backscattering.

The phenomenon of enhanced backscattering (also known as coherent backscattering), an object of substantial scientific interest, has awaited application to tissue optics for the past two decades. Here we demonstrate, for the first time to our knowledge, depth-resolved spectroscopic elastic light scattering measurements in tissue by use of low-coherence enhanced backscattering (LEBS). We achieve the depth resolution by exploiting the nature of the LEBS peak that contains information about a wide range of tissue depths. We further demonstrate that depth-resolved LEBS spectroscopy has the potential to identify the origin of precancerous transformations in the colon at an early, previously undetectable stage.

Adenoma↗

PubMed2005

Low-coherent backscattering spectroscopy for tissue characterization.

Although the phenomenon of coherent backscattering (CBS) in nonbiological media has generated substantial research interest, observing CBS in biological tissue has been extremely difficult. Here we show that the combination of low-spatial-coherence, broadband illumination, and low-temporal-coherence, spectrally resolved detection significantly facilitates CBS observation in biological tissue and other random media with long-transport mean-free path lengths, which have been previously beyond the reach of conventional CBS investigations. Furthermore, we demonstrate that depth-selective, speckle-free, low-coherent backscattering spectroscopy has the potential to diagnose the earliest, previously undetectable, precancerous alterations in the colon by means of probing short light paths.

Animals↗

PubMed2005

Spectral markers in preneoplastic intestinal mucosa: an accurate predictor of tumor risk in the MIN mouse.

BACKGROUND: We have reported recently that microarchitectural analysis of the histologically normal mucosa using a novel optics technology, four-dimensional elastic light scattering fingerprinting (ELF), provided unprecedented sensitivity for early detection of colon carcinogenesis. In the present study, we explored the ability of four-dimensional ELF to identify an inherited predisposition to colorectal cancer, an issue of considerable importance for optimizing population screening strategies. METHODS: We used the MIN mouse, a model whose germ line adenomatous polyposis coli truncation leads to spontaneous intestinal tumorigenesis, thus replicating the human syndrome, familial adenomatous polyposis. Spectral markers were assessed by four-dimensional ELF analysis in MIN mice at preneoplastic time points and compared with age-matched controls (C57BL6 mice with wild-type adenomatous polyposis coli). To assess the responsiveness of spectral markers to chemopreventive agents, a subset of MIN mice was supplemented with celecoxib 1,500 ppm. RESULTS: Spectral slope, fractal dimension, and principal component 3 were dramatically altered in the uninvolved MIN mouse mucosa at the earliest time points. Furthermore, alteration in spectral variables increased over time, consonant with the microarchitectural underpinnings of subsequent tumorigenesis. Additionally, these markers spatially correlated with future adenoma development (small intestine > colon). Short-term treatment with the potent chemopreventive agent, celecoxib, resulted in near normalization of fractal dimension and principal component 3. CONCLUSIONS: We report, for the first time, that spectral markers, assayed by four-dimensional ELF, were able to sensitively identify a genetic predisposition for intestinal tumorigenesis before the occurrence of phenotypic manifestations. Moreover, the reversal of spectral markers by celecoxib treatment supports the neoplastic relevance.

Animals↗

PubMed2004

Coherent backscattering spectroscopy.

Coherent backscattering (CBS) of light in random media has been previously investigated by use of coherent light sources. Here we report a novel method of CBS measurement that combines low spatial coherence, broadband illumination, and spectrally resolved detection. We show that low spatial coherence illumination leads to an anomalously broad CBS peak and a dramatic speckle reduction; the latter is further facilitated by low temporal coherence detection. Thus CBS can be observed in biological tissue and other media that previously were beyond the reach of conventional CBS measurements. We also demonstrate, for the first time to our knowledge, spectroscopic analysis of CBS. CBS spectroscopy may find important applications in probing random media such as biological tissue in which depth-selective measurements are crucial.

Animals↗

PubMed2004

Variation of corneal refractive index with hydration.

We report the effect of changes in the corneal hydration on the refractive index of the cornea. Using optical coherence tomography (OCT), the geometrical thickness and the group refractive index of the bovine cornea were derived simultaneously as the corneal hydration was varied. The corneal hydration was then calculated from the corneal thickness. The group refractive index of the cornea increased non-linearly as the cornea dehydrated. In addition, a simple mathematical model was developed, based on the assumption that changes in corneal hydration occur only in the interfibrilar space with constant water content within the collagen fibrils. Good agreement between the experimental results and the mathematical model supports the assumption. The results also demonstrate that the measurement of refractive index is a quantitative indicator of corneal hydration.

Animals↗

PubMed2004

Four-dimensional elastic light-scattering fingerprints as preneoplastic markers in the rat model of colon carcinogenesis.

BACKGROUND & AIMS: Identification of preneoplastic changes in histologically normal epithelium (the "field effect") could provide a powerful screening tool for colorectal cancer. However, to date, reliable detection has not been possible. We have recently developed a new generation of optical technology, 4-dimensional elastic light-scattering fingerprinting (4D-ELF), which enables us to probe the nanoscale/microscale architecture of living cells. We therefore investigated whether 4D-ELF would be able to identify preneoplastic changes in the colonocytes of the azoxymethane (AOM)-treated rat model of colon carcinogenesis. METHODS: Forty-eight Fisher 344 rats were randomized to either 2 weekly injections of AOM or saline. Animals were killed 2-20 weeks after the second injection of AOM. Colons were removed and subjected to 4D-ELF analysis, with a subset undergoing assessment of aberrant crypt foci (ACF). All AOM-treated animals were compared with age-matched saline-treated controls. RESULTS: AOM-induced ACF became apparent at approximately 4-6 weeks and continued to increase over time. ACF were predominantly located in the distal colon. At 2 weeks (before development of ACF), there were marked changes in a number of 4D-ELF signatures. The relevance to carcinogenesis of these 4D-ELF-detected microarchitectural abnormalities is supported by their spatial and temporal correlation with subsequent development of ACF. All changes reported were highly statistically significant. CONCLUSIONS: We show that probing the nanoscale cellular architecture with 4D-ELF provided an unprecedented tool for detecting the earliest stages of colon carcinogenesis. Future studies are necessary to explore the clinical applicability of this technology and elucidate the biological determinants of these microarchitectural changes.

Animals↗

PubMed2003

Phase-slope and group-dispersion calculations in the frequency domain by simple optical low-coherence reflectometry.

We report a new method by which phase slope and group dispersion can be calculated with a simple optical low-coherence reflectometer to quantify physiological conditions. A discrete-time signal processing algorithm based on the first and second derivatives of the phase with respect to wave number was developed from discrete-time Fourier properties. The algorithm avoids the 2pi ambiguity associated with most phase unwrapping. Experimental data collected by use of well-characterized optical materials validated the algorithm, which was minimally sensitive to phase noise. The group dispersion of bovine cornea was measured at various hydrations and was significantly dependent on hydration. The results suggest that group dispersion is an indicator of corneal alterations.

Algorithms↗