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

The future of medical diagnostics: Review paper

While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis. We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions. © 2011 Jerjes et al; licensee BioMed Central Ltd

Emerging Optical Techniques for Detection of Oral, Cervical and Anal Cancer in Low-Resource Settings

Cancers of the oral and anogenital regions are a growing global health problem that disproportionately impact women and men living in developing countries. The high death rate in developing countries is largely due to the fact that these countries do not have the appropriate medical infrastructure and resources to support the organized screening and diagnostic programs that are available in the developed world. Emerging optical diagnostics techniques, such as optical spectroscopy, reflectance imaging, and fluorescence imaging, are noninvasive techniques that are sensitive to multiple cancer biomarkers and have shown the potential as a cost–effective and fast tool for diagnosis of early precancerous changes in the cervix, oral cavity and anus. This paper provides a review of current strategies for prevention, screening and diagnostic tests of oral, cervical and anal cancers and development in optical diagnostic techniques that could potentially be used to improve current practice in resource–limited settings

Quantitative near-infrared spectroscopy of cervical dysplasia in vivo

The aims of this study were: (i) to quantify near-infrared optical properties of normal cervical tissues and high-grade squamous intra-epithelial lesions (H-SIL); (ii) to assess the feasibility of differentiating normal cervical tissues from H-SIL on the basis of these properties; and (iii) to determine how cervical tissue optical properties change following photodynamic therapy (PDT) of H-SIL in vivo. Using the frequency domain photon migration technique, non-invasive measurements of normal and dysplastic ecto-cervical tissue optical properties, i.e. absorption (μa) and effective scattering coefficients, and physiological parameters, i.e. tissue water and haemoglobin concentration, percentage oxygen saturation (%SO2), were performed on 10 patients scheduled for PDT of histologically-proven H-SIL. Cervix absorption and effective scattering parameters were up to 15% lower in H-SIL sites compared with normal cervical tissue for all wavelengths studied (674, 811, 849, 956 nm). Following PDT, all μa values increased significantly, due to elevated tissue blood and water content associated with PDT-induced hyperaemia and oedema. Tissue total haemoglobin concentration ([TotHb]) and arterio-venous oxygen saturation measured in H-SIL sites were lower than normal sites ([TotHb]: 88.6 ± 35.8 μmol/l versus 124.7 ± 22.6 μmol/l; %SO2: 76.5 ± 14.7% versus 84.9 ± 3.4%

Near real time confocal microscopy of Ex Vivo cervical tissue: detection of dysplasia

textRecent studies have shown the ability of confocal microscopy to noninvasively image cells in vivo in real time. This ability to visualize nuclei in vivo shows the potential of confocal microscopy to dramatically improve the prevention, detection and therapy of epithelial cancers. More exciting is the potential to quantitatively measure nuclear morphometry providing a basis to automate the cancer detection process. This dissertation describes studies exploring this potential in ex vivo cervical tissue using acetic acid as a nuclear contrast agent. First the use of acetic acid was demonstrated to improved contrast in confocal images of cervical tissue sufficiently to allow segmentation. Segmentation is robust throughout the epithelium in most normal tissue and upper portions of tissue diagnosed with severe dysplasia. Based upon this segmentation, quantitative feature measurements were extracted from confocal images of cervical tissue in a pilot study to determine if the features would aide in the detection of dysplasia. Simultaneously, a qualitative review of confocal images was performed by untrained reviewers and compared with clinical colposcopic impressions, the standard clinical tool aiding in dysplasia detection. The sensitivity and specificity of both the qualitative (95% and 69%) and quantitative (100% and 91%) review were improved compared to colposcopic review (91% and 62%). Finally the ability of confocal microscopy to produce 3D images was explored as a further means to improve dysplasia detection. Based upon Beer’s equation for light attenuation, the scattering coefficient was extracted from 3D image sets of ex vivo cervical tissue and compared with histology from the same precancerous lesion. The results suggested a possible correlation between high scattering values and the presence of dysplasia. Quantitative 3D features were also extracted from 3D image sets and correlated with the presence of CIN 2/3. Increased separation between normal and CIN 2/3 biopsies was produced using the 3D features as compared to the 2D. More importantly, when additional information (scattering coefficient) is combined with the 2D features, the ability to distinguish between normal and CIN 2/3 is 100% accurate in this small sample set.Electrical and Computer Engineerin

The Effect of Probe Pressure on In Vivo Single Fiber Reflectance Spectroscopy

Introduction: Single fiber reflectance spectroscopy (SFRS) is a noninvasive procedure to quantitate tissue absorption and scattering properties. It can be used to diagnose different diseases such as malignancy and pre-cancerous conditions. The measurement is done with a fiber optic probe in contact with the tissue surface. Herein, the effect of probe pressure on the extracted parameters from human lip spectra was studied.Methods: Thirty-three normal subjects were examined with three exerted pressure levels on the right, middle and left parts of their lips.Results: The results showed variation of spectroscopic parameters with different pressure levels. However, the effect was seen between a very mild contact (pressure 1) and the other reasonably practical pressure levels normally used in the medical centers.Conclusion: SFRS can be used as a reliable diagnostic tool in clinics

Emerging Technologies, Signal Processing and Statistical Methods for Screening of Cervical Cancer In Vivo: Are They Good Candidates for Cervical Screening?

The current cervical cancer screening test (the Pap smear) is a manual cytological procedure. This cytology test has various limitations and many errors. Excellent candidates for improving the performance of the cervical cancer screening procedure are electro-optical systems (EOSs), used for assessment of the cervical cancer precursors in vivo, such as digital spectroscopy, digital colposcopy and bioelectrical phenomena-based systems. These EOSs use the advantages of signal processing methods and can replace the qualitative assessments, with objective metrics. The EOSs can be used as an adjunct to the current screener or as a primary screener. We analyse and discuss the effectiveness of the signal processing and statistical methods for diagnosis of cervical cancer in vivo. This analysis is reinforced by the presentation of the scientific and clinical contributions of these methods in clinical practice. As a result of this analysis, we outline and discuss the well-established estimates of the signal processing features and the ambiguous features, that are used for classification of the cervical pre-cancer in vivo

Submicron scale tissue multifractal anisotropy in polarized laser light scattering

The spatial fluctuations of the refractive index within biological tissues exhibit multifractal anisotropy, leaving its signature as a spectral linear diattenuation of scattered polarized light. The multifractal anisotropy has been quantitatively assessed by the processing of relevant Mueller matrix elements in the Fourier domain, utilizing the Born approximation and subsequent multifractal analysis. The differential scaling exponent and width of the singularity spectrum appear to be highly sensitive to the structural multifractal anisotropy at the micron/sub-micron length scales. An immediate practical use of these multifractal anisotropy parameters was explored for non-invasive screening of cervical precancerous alterations ex vivo, with the indication of a strong potential for clinical diagnostic purposes

Early diagnosis of cancer using LSS

Thesis (Ph. D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2001.Includes bibliographical references.This thesis presents a novel optical technique, light scattering spectroscopy (LSS), developed for quantitative characterization of tissue morphology as well as in vivo detection and diagnosis of the diseases associated with alteration of normal tissue structure such as precancerous and early cancerous transformations in various epithelia. LSS employs a wavelength dependent component of light scattered by epithelial cells to obtain information about subcellular structures, such as cell nuclei. Since nuclear atypia is one of the hallmarks of precancerous and cancerous changes in most human tissues, the technique has the potential to provide a broadly applicable means of detecting epithelial precancerous lesions and noninvasive cancers in various organs, which can be optically accessed either directly or by means of optical fibers. We have developed several types of LSS instrumentation including 1) endoscopically compatible LSS-based fiber-optic system;(cont.) 2) LSS-based imaging instrumentation, which allows mapping quantitative parameters characterizing nuclear properties over wide, several cm2, areas of epithelial lining; and 3) scattering angle sensitive LSS instrumentation (a/LSS), which enables to study the internal structure of cells and their organelles, i.e. nuclei, on a submicron scale. Multipatient clinical studies conducted to test the diagnostic potential of LSS in five organs (esophagus, colon, bladder, cervix and oral cavity) have shown the generality and efficacy of the technique and indicated that LSS may become an important tool for early cancer detection as well as better biological understanding of the disease.by Vadim Backman.Ph.D