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

Design of a Novel Low Cost Point of Care Tampon (POCkeT) Colposcope for Use in Resource Limited Settings

Introduction: Current guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA) of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope) for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies. Results: Our POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems. Methods: Rapid 3D printing, consumer grade light sources, and cameras were used to construct the TVDC. The TVDC’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes, and crossed polarizers provide a reduction in glare. Evaluation was performed using standard optical imaging targets to assess the TVDC against the state of the art digital colposcope and other VIA technologies. Results: Our TVDC has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our TVDC capturing images of comparable quality to commercial systems. Conclusion: The TVDC is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system will be useful for increasing access to cervical cancer screening and diagnostics in resource-limited settings by providing a more readily portable and easy to use device for medical personnel.The image data and support information that is published in the article "Design of a Novel Low Cost Trans-Vaginal Digital Colposcope for use in Resource Limited Settings" are available at: http://dukespace.lib.duke.edu/dspace/handle/10161/8357.National Institutes of Health (US) 5R21CA162747-0

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

Near-Infrared Confocal Raman Spectroscopy for Real-Time Diagnosis of Cervical Precancer

Ph.DDOCTOR OF PHILOSOPH

Polarimetric Imaging of the Uterine Cervix

Cervical cancer is the fourth most common cancer in women, with more than half a million women diagnosed each year due to persistent human papillomavirus (HPV) infection and a mortality of 311,000 women. According to the World Cancer Research Fund, developing countries have 84% of the global burden of the disease and 80% of the mortality due to a lack of effective screening programs. Several screening techniques have been developed and implemented to aid in low resource setting cervical screening, however, most require physician interpretation of color images. Other modalities utilize contrast agents to highlight pathological tissue but have small field of view. This dissertation investigates the use of polarimetric imaging techniques to image uterine cervix with particular focus to the needs of underserved communities. We have used Mueller matrix imaging, to noninvasively image the uterine cervix in vivo. Mueller matrix (MM) can provide structural information of the cervix extracellular matrix (ECM) that could be leveraged for early diagnosis of cervical cancer and other pathologies of the uterine cervix. We have developed a Savart-based portable Mueller matrix polarimeter to conduct a pilot study to characterize polarimetrically healthy human cervixes. The results showed high depolarization and retardance, as is expected of healthy tissue. The availability of new equipment, such as microgrid polarized cameras, led to the simplification of the polarimetric setup from a 4 x 4 MM to a reduced 3 x 4 MM. To facilitate image acquisition using this camera, we have devised a novel algorithm capable of decomposing the Mueller Matrix from its reduced (3 x 4) form. The algorithm was compared and shown to provide similar results to two established decomposition methods. Finally, we have used this approach to obtain depolarization and azimuthal angle values of biological tissue including ex vivo samples and in vivo cervix. This works paves the way to non-invasive studies of cervical structure in vivo

Validation of whole slide imaging in the primary diagnosis of gynaecological pathology in a University Hospital

AIMS: Experience in the use of whole slide imaging (WSI) for primary diagnosis in pathology is very limited. We aimed to determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of routine gynaecological biopsies. METHODS: All gynaecological specimens (n=452) received over a 2-month period at the Department of Pathology of the Hospital Clinic of Barcelona were analysed blindly by two gynaecological pathologists, one using CLM and the other WSI. All slides were digitised in a Ventana iScan HT (Roche diagnostics) at 200×. All discrepant diagnoses were reviewed, and a final consensus diagnosis was established. The results were evaluated by weighted κ statistics for two observers. RESULTS: The level of interobserver agreement between WSI and CLM evaluations was almost perfect (κ value: 0.914; 95% CI 0.879 to 0.949) and increased during the study period: κ value 0.890; 95% CI 0.835 to 0.945 in the first period and 0.941; 95%; CI 0.899 to 0.983 in the second period. Major discrepancies (differences in clinical management or prognosis) were observed in 9 cases (2.0%). All discrepancies consisted of small lesions (8 high grade squamous intraepithelial lesions of the uterine cervix, one lymph node micrometastasis of an ovarian carcinoma) underdiagnosed or missed in the WSI or the CLM evaluation. Discrepancies with no or minor clinical relevance were identified in 3.8% of the biopsies. No discrepancy was related to the poor quality of the WSI image. CONCLUSIONS: Diagnosis of gynaecological specimens by WSI is accurate and may be introduced into routine diagnosis

Laser doppler perfusion imaging of the normal and diseased vulva.

Vulval lichen sclerosus (LS) and high-grade intraepithelial neoplasia (VIN 3) are two common and distressing diseases. Significant morbidity is caused by symptoms of persistent pruritus and surgical treatment of skin areas suspicious of malignancy. The risk of developing cancer in a background of LS and VIN 3 is poorly defined. The methods currently available for clinical assessment of the vulva are limited. There is abundant research on the application of the LASER Doppler technique - laser Doppler Flowmetry (LDF) - showing changes in perfusion within the small blood vessels of the skin as a useful parameter for more accurate disease classification. There is also research on immunohistochemical microvessel density (MVD) studies showing increases in blood supply in tissues prone to develop cancer or as a prognostic marker of cancer outcome. The Laser Doppler perfusion imager (LDPI) provides a rapid, real time, non-invasive and non-contact method to measure skin blood flow in an area as opposed to a single point by the LDF, making the LDPI more suitable for application to the vulva. This thesis reports for the first time, the application of the LDPI to the vulva. Initially the LDPI was applied to the clinically normal vulva to study perfusion variance related to menstrual cycle, age and local skin temperature provocation. The application was then extended to vulval disease, LS and VIN 3, and validated against morphological differences in MVD. The LDPI and MVD studies suggest that in VIN 3 there is an actual increase in skin perfusion. In LS the situation is more complex and suggests that the LDPI measured perfusion at a greater depth than the MVD. Studies on base line perfusion variance of vulval LS to topical therapy show that there is no overall difference in baseline perfusion in spite of symptom improvement. Temperature provocation studies suggest differences in skin blood flow response in diseased compared to the normal vulva

Dosimetric and radiobiological evaluation of combined course of radiation therapy for locally advanced cervical cancer based on different techniques for dose delivery

Рак шейки матки является четвертым наиболее распространенным злокачественным заболеванием у женщин во всем мире. Брахитерапия (БТ) - это шаг в лучевой терапии локально распространенного рака шейки матки, но для некоторых пациентов БТ не подходит по медицинским, религиозным или этическим причинам. Для этих пациентов весь курс лечения должен проводиться с использованием только EBRT, поэтому в этом исследовании предпринята попытка оценить различные методы комбинированной лучевой терапии - не включая BT - для лечения рака шейки матки, чтобы определить лучшую технику среди российских пациентов в Томске.Cervical cancer is the fourth most common malignancy in females worldwide. Brachytherapy (BT) is step in radiotherapy of locally advanced cervical cancer, but for some patients BT not an option due to medical, religious or ethical reasons. For these patients, the whole treatment course should be given using only EBRT, so this study tries to evaluate different techniques of combined Radiotherapy -not include BT- for cervical cancer to detect the best technique among Russian patients at Tomsk