Tissue characterization and detection of dysplasia using scattered light

Paper presented at the 2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro, Arlington, VA.In this paper, the structural parameters of dysplasia formation in the epithelial tissue are estimated using a stochastic decomposition algorithm (SDM) by means of scattered light. We extract texture parameters obtained from the decomposition that capture the signature of dysplasia formation. These parameters include the number and mean energy of coherent scatterers; deviation from Rayleigh scattering; average energy of diffuse scatterers; and normalized correlation coefficient. The tests are performed on simulations, and tissue-mimicking phantom data. The simulations are based on the light scattered from the cells with varying parameters such as, index of refraction, number of cells, and size of cells. The obtained results demonstrate the proof-of-concept in being able to differentiate between tissue structures that give rise to changes in cell morphology as well as other physical properties such as change in index of refraction. Fusing all the estimated parameter set together results in the differentiation performance (Az value) up to 1(perfect detection) for simulated data, and Az>0.927 for the phantom data

Differing self-similarity in light scattering spectra: A potential tool for pre-cancer detection

The fluctuations in the elastic light scattering spectra of normal and dysplastic human cervical tissues analyzed through wavelet transform based techniques reveal clear signatures of self-similar behavior in the spectral fluctuations. Significant differences in the power law behavior ascertained through the scaling exponent was observed in these tissues. The strong dependence of the elastic light scattering on the size distribution of the scatterers manifests in the angular variation of the scaling exponent. Interestingly, the spectral fluctuations in both these tissues showed multi-fractality (non-stationarity in fluctuations), the degree of multi-fractality being marginally higher in the case of dysplastic tissues. These findings using the multi-resolution analysis capability of the discrete wavelet transform can contribute to the recent surge in the exploration for non-invasive optical tools for pre-cancer detection.Comment: 13 pages, 14 figure

Oblique Polarized Reflectance Spectroscopy for Depth Sensitive Measurements in the Epithelial Tissue

Optical spectroscopy has shown potential as a tool for precancer detection by discriminating alterations in the optical properties within epithelial tissues. Identifying depth-dependent alterations associated with the progression of epithelial cancerous lesions can be especially challenging in the oral cavity due to the variable thickness of the epithelium and the presence of keratinization. Optical spectroscopy of epithelial tissue with improved depth resolution would greatly assist in the isolation of optical properties associated with cancer progression. Here, we report a fiber optic probe for oblique polarized reflectance spectroscopy (OPRS) that is capable of depth sensitive detection by combining the following three approaches: multiple beveled fibers, oblique collection geometry, and polarization gating. We analyze how probe design parameters are related to improvements in collection efficiency of scattered photons from superficial tissue layers and to increased depth discrimination within epithelium. We have demonstrated that obliquely-oriented collection fibers increase both depth selectivity and collection efficiency of scattering signal. Currently, we evaluate this technology in a clinical trial of patients presenting lesions suspicious for dysplasia or carcinoma in the oral cavity. We use depth sensitive spectroscopic data to develop automated algorithms for analysis of morphological and architectural changes in the context of the multilayer oral epithelial tissue. Our initial results show that OPRS has the potential to improve the detection and monitoring of epithelial precancers in the oral cavity.Biomedical Engineerin

Optical Molecular Imaging in the Gastrointestinal Tract

Recent developments in optical molecular imaging allow for real-time identification of morphological and biochemical changes in tissue associated with gastrointestinal neoplasia. This review summarizes widefield and high resolution imaging modalities currently in pre-clinical and clinical evaluation for the detection of colorectal cancer and esophageal cancer. Widefield techniques discussed include high definition white light endoscopy, narrow band imaging, autofluoresence imaging, and chromoendoscopy; high resolution techniques discussed include probe-based confocal laser endomicroscopy, high-resolution microendoscopy, and optical coherence tomography. Finally, new approaches to enhance image contrast using vital dyes and molecular-specific targeted contrast agents are evaluated

Early detection of curable precancerous lesions in the oral cavity using polarized reflectance spectroscopy

textIn 2004, the American Cancer Society estimates that more than 1,500 deaths a day associated with cancer will occur. For all cancers, the five-year survival rate is greater if diagnosis is made at an early stage of cancer development. The focus of this dissertation is on the development of a highly selective and sensitive non-invasive optical device for the early detection of epithelial precancers, which has enormous potential to reduce patient morbidity and mortality. Specifically, this dissertation will concentrate on the assessment of the polarized reflectance spectroscopy (PRS) to detect and diagnose early curable precancerous lesions within the oral cavity. PRS is a variation of elastic scattering spectroscopy which is sensitive to important morphological indicators of early precancer, such as scatterer size and refractive index. In this dissertation I will present a fiber optic probe that combines polarized illumination and detection with an angled distal probe geometry to detect the size dependent scattering within the epithelial layer of tissue, where most cancer originate. This technique allows a simple Mie theory based model to be used to extract the nuclear sizes. Tissue phantoms that mimic the two-layered scattering structure of mucosal tissue were used to test the feasibility of PRS to extract scatter sizes. Results of these studies showed excellent agreement between spectroscopically derived scatter sizes and direct microscopy measurements. In vivo measurements within the oral cavity of normal volunteers also yielded nuclear sizes that corresponded very well to published values. The PRS device was found to be capable of discriminating normal oral mucosa tissue from severe dysplasia in a collaborative pilot clinical trial of 21 patients, at the UT MD Anderson Cancer Center. Nuclear morphology extracted from the polarized spectroscopy measurements compared very well to quantitative histopathology. Overall this dissertation gives a thorough basis for a larger statistically significant clinical trial to be performed to determine the sensitivity and specificity of polarized reflectance spectroscopy as a screening and diagnostic instrument in the oral cavity. The work in this dissertation lays the foundation for future exploration of the optical scattering properties polarized light within tissue for clinical applications.Physic

Machine learning classification of human joint tissue from diffuse reflectance spectroscopy data

Objective: To assess if incorporation of DRS sensing into real-time robotic surgery systems has merit. DRS as a technology is relatively simple, cost-effective and provides a non-contact approach to tissue differentiation. Methods: Supervised machine learning analysis of diffuse reflectance spectra was performed to classify human joint tissue that was collected from surgical procedures. Results: We have used supervised machine learning in the classification of a DRS human joint tissue data set and achieved classification accuracy in excess of 99%. Sensitivity for the various classes were; cartilage 99.7%, subchondral 99.2%, meniscus 100% and cancellous 100%. Full wavelength range is required for maximum classification accuracy. The wavelength resolution must be larger than 8nm. A SNR better than 10:1 was required to achieve a classification accuracy greater than 50%. The 800-900nm wavelength range gave the greatest accuracy amongst those investigated. Conclusion: DRS is a viable method for differentiating human joint tissue and has the potential to be incorporated into robotic orthopaedic surgery

Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues

The autofluorescence (AF) characteristics of endogenous fluorophores allow the label-free assessment and visualization of cells and tissues of the human body. While AF imaging (AFI) is well-established in ophthalmology, its clinical applications are steadily expanding to other disciplines. This review summarizes clinical advances of AF techniques published during the past decade. A systematic search of the MEDLINE database and Cochrane Library databases was performed to identify clinical AF studies in extra-ophthalmic tissues. In total, 1097 articles were identified, of which 113 from internal medicine, surgery, oral medicine, and dermatology were reviewed. While comparable technological standards exist in diabetology and cardiology, in all other disciplines, comparability between studies is limited due to the number of differing AF techniques and non-standardized imaging and data analysis. Clear evidence was found for skin AF as a surrogate for blood glucose homeostasis or cardiovascular risk grading. In thyroid surgery, foremost, less experienced surgeons may benefit from the AF-guided intraoperative separation of parathyroid from thyroid tissue. There is a growing interest in AF techniques in clinical disciplines, and promising advances have been made during the past decade. However, further research and development are mandatory to overcome the existing limitations and to maximize the clinical benefits

Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime −570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens

Optical biopsy of epithelial cancers by optical coherence tomography

Optical coherence tomography (OCT) is an optical technique that measures the backscattering of near-infrared light by tissue. OCT yields in 2D and 3D images at micrometer-scale resolution, thus providing optical biopsies, approaching the resolution of histopathological imaging. The technique has shown to allow in vivo differentiation between benign and malignant epithelial tissue, through qualitative assessment of OCT images, as well as by quantitative evaluation, e.g., functional OCT. This study aims to summarize the principles of OCT and to discuss the current literature on the diagnostic value of OCT in the diagnosis of epithelial (pre)malignant lesions. The authors did a systematic search of the electronic databases PubMed and Embase on OCT in the diagnostic process of (pre)malignant epithelial lesions. OCT is able to differentiate between benign and (pre)malignant lesions of epithelial origin in a wide variety of tissues. In this way, OCT can detect skin cancers, oral, laryngeal, and esophageal cancer as well as genital and bladder cancer. OCT is an innovative technique which enables an optical biopsy of epithelial lesions. The incorporation of OCT in specific tools, like handheld and catheter-based probes, will further improve the implementation of this technology in daily clinical practice

Tissue multifractality and Born approximation in analysis of light scattering: a novel approach for precancers detection

Multifractal, a special class of complex self-affine processes, are under recent intensive investigations because of their fundamental nature and potential applications in diverse physical systems. Here, we report on a novel light scattering-based inverse method for extraction/quantification of multifractality in the spatial distribution of refractive index of biological tissues. The method is based on Fourier domain pre-processing via the Born approximation, followed by the Multifractal Detrended Fluctuation Analysis. The approach is experimentally validated in synthetic multifractal scattering phantoms, and tested on biopsy tissue slices. The derived multifractal properties appear sensitive in detecting cervical precancerous alterations through an increase of multifractality with pathology progression, demonstrating the potential of the developed methodology for novel precancer biomarker identification and tissue diagnostic tool. The novel ability to delineate the multifractal optical properties from light scattering signals may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin