Natalia M. Shakhova

Novel algorithm of processing optical coherence tomography images for differentiation of biological tissue pathologies

A numerical algorithm based on a small-angle approximation of the radiative transfer equation (RTE) is developed to reconstruct scattering characteristics of biological tissues from optical coherence tomography (OCT) images. According to the algorithm, biological tissue is considered to be a layered random medium with a set of scattering parameters in each layer: total scattering coefficient, variance of a small-angle scattering phase function, and probability of backscattering, which fully describe the OCT signal behavior versus probing depth. The reconstruction of the scattering parameters is performed by their variation to fit the experimental OCT signal by the theoretical one using a time-saving genetic algorithm. The proposed reconstruction procedure is tested on model media with known scattering parameters. The possibility to estimate scattering parameters from OCT images is studied for various regimes of OCT signal decay. The developed algorithm is applied to reconstruct optical characteristics of epithelium and stroma for normal cervical tissue and its pathologies, and the potential to distinguish between the types of pathological changes in epithelial tissue by its OCT images is demonstrated.

Endoscopic OCT with forward-looking probe: clinical studies in urology and gastroenterology.

In the current paper we present results of application of endoscopic time-domain OCT (EOCT) with lateral scanning by forward looking miniprobe. We analysed material of clinical studies of 554 patients: 164 patients with urinary bladder pathology, and 390 with gastrointestinal tract pathology. We reviewed the materials obtained in different clinics using the OCT device elaborated at the Institute of Applied Physics. We demonstrate results of EOCT application in detection of early cancer and surgery guidance, examples of combined use of OCT and fluorescence imaging. As a result, we show the diagnostic accuracy of EOCT in specific clinical tasks. The sensitivity of EOCT cancer determination in Barretts esophagus is from 71% to 85% at different stages of neoplasia with specificity 68% for all stages. As for bladder carcinoma, the sensitivity and specificity are 85% and 68%, respectively. In colon dysplasia EOST demonstrates high efficacy: sensitivity 92% and specificity 84%.

Criteria for pathology recognition in optical coherence tomography of fallopian tubes

An increase of infertility and chronic pelvic pains syndrome, a growing level of latent diseases of this group, as well as a stably high percentage (up to 25% for infertility and up to 60% for the chronic pelvic pains syndrome) of undetermined origin raises the requirement for novel introscopic diagnostic techniques. We demonstrate abilities of optical coherence tomography (OCT) as a complementary technique to laparoscopy in diagnostics of fallopian tubes pathologies. We have acquired OCT images of different parts of fallopian tubes in norm and with morphologically proven pathology. Based on comparative analysis of the OCT data and the results of histological studies, we have worked out the subjective OCT criteria for distinguishing between unaltered and pathologic tissues. The developed criteria are verified in blind recognition tests. Diagnostic efficacy of OCT diagnostics in the case ofpelvic inflammatory diseases has been statistically evaluated, and high diagnostic accuracy (88%) is shown. Basing of the subjective criteria, an attempt to develop independent criteria aimed for automated recognition of pathological states in fallopian tubes is undertaken. Enhanced diagnostic accuracy (96%) of the developed independent criteria is demonstrated.

Optical coherence tomography in diagnostics of precancer and cancer of human bladder

Our goal was statistical assessment of the in vivo cystoscopic optical coherence tomography (OCT) ability to detect neoplasia in human urinary bladder. We analyzed major reasons of false positive and false negative image recognition results. Optical coherence tomography was performed to image the bladder during cystoscopy. The study enrolled 63 patients with suspicion for bladder cancer and scheduled for cystoscopy. The diagnosis was established by histopathology examination of a biopsy. Each biopsy site was examined by OCT. Benign conditions were diagnosed for 31 patients, and dysplasia or carcinoma were diagnosed for 32 patients. Six physicians blinded to all clinical data participated in the dichotomy recognition (malignant or benign) of the OCT images. 98% sensitivity and 72% specificity for the OCT recognition of dysplastic/malignant versus benign/reactive conditions of the bladder are demonstrated. Total error rate was 14.8%. The interobserver agreement multi-rater kappa coefficient is 0.80. The superficial and invasive bladder cancer and high-grade dysplasia were recognized with minimum error rate ranging from 0 to 3.3%. High sensitivity and good specificity of the OCT method in the diagnostics of bladder neoplasia makes OCT a promising complementary cystoscopic technique for non-invasive evaluation of zones suspicious for high-grade dysplasia and cancer.

Blinded recognition of optical coherence tomography images of human mucosa precancer

In vivo endoscopic optical coherence tomography (OCT) was performed in 154 patients with pathologic lesions, suspicious for high-grade dysplasia, intramucosal or early microinvasive cancer. One group of seven physicians and another of six, familiar with OCT, participated in the blinded recognition of benign and neoplastic conditions in different types of mucous membranes. The result for the OCT sensitivity for malignancy detection in these types of mucosa is 83 - 98%, specificity 71 - 91%. The accuracy was 81 - 87%. Recognition error rate is smaller for high-grade dysplasia and invasive cancer in urinary bladder (3.3% - 1.5%), and higher for the uterine cervix (23% - 11%) and for larynx (45.7% - 3.4%). The kappa coefficient for interobserver agreement was 0.65-0.83.

Optical coherence tomography in diagnostics and guided surgery of bladder cancer

We performed blind recognition of optical coherence tomography (OCT) images of human urinary bladder for diagnostics of carcinoma and premalignant conditions. OCT images of 63 patients were acquired in vivo during cystoscopic examination. The malignant/premalignant conditions were differentiated from benign/reactive with 98% sensitivity and 72% specificity. OCT was also used for intraoperative monitoring of zones around the tumor for adequate resection (31 patients). OCT - guided planning of the resection margin and examination of the postoperative resection line after transurethral resection (TUR) was performed.

Optical coherence tomography: potentialities in clinical practice

Clinical studies using OCT involved 2000 patients in various fields of medicine such as gastroenterology, urology, laryngology, gynecology, dermatology, stomatology, etc. Layered high-contrast images were typical for benign epithelial conditions. OCT distinguish in mucosae: epithelium, connective tissue layer, and smooth-muscle layer. Various benign processes occurring in mucosa manifest in OCT images as changes in the epithelial height, scattering properties and the course of the basement membrane. Lack of the layered structural pattern is the main criterion for dysplastic / malignant images. In clinic: OCT data may be critical for choosing a tissue site for excisional biopsy, OCT can detect tumor borders and their linear dimensions, OCT can be used to plan a resection line in operations and to control adequacy of resection, to monitor whether reparative processes are timely and adequate. OCT sensitivity of the uterine cervix, urinary bladder and larynx is 82, 98, 77%, respectively, specificity - 78, 71, 96%, diagnostic accuracy - 81, 85, 87% with significantly good agreement index of clinicians kappa - 0.65, 0.79, 0.83 (confidence intervals: 0.57-0.73; 0.71-0.88; 0.74-0.91). Error in detection of high grade dysplasia and microinvasive cancer is 21.4% in average. Additional modification of OCT (cross-polarisation OCT, OCM), development of the procedure (biotissue compression, application of chemical agents) can improve the specificity and sensitivity of traditional modality.

Novel optical spectroscopy system for breast cancer diagnostics

We report on development of minimally invasive system for immediate diagnostics of breast cancer and on the results of its pilot clinical testing. The system designed by BioTelligent Inc is based on analysis of optical diffusion spectra (ODS) measured by a probe inserted into breast tissue during standard punch biopsy. Analysis of scattered spectra aimed to distinction of benign tumors from malignant ones is done by original procedure of data processing. Clinical testing of the created diagnostic system has been performed by classification of spectra collected from 146 patients with previously detected mammary neoplasms. The data of ODS study in each patient have been compared to the results of histology. The proposed technique has to date demonstrated sensitivity of 96%, specificity of 80% and diagnostic accuracy of 88%. These values are expected to improve as the data sets continue to grow and more sophisticated data processing is employed.

OCT visualization of acute radiation mucositis: pilot study

We present pilot results in optical coherence tomography (OCT) visualization of normal mucosa radiation damage. 15 patients undergoing radiation treatment of head and neck cancer were enrolled. OCT was used to monitor the mucositis development during and after treatment. OCT can see stages of radiation mucositis development, including hidden ones, before any clinical manifestations.

Topical problems of biophotonics.

Optical methods in biomedicine have experienced an outstanding development in recent decades and are currently successfully translated from research laboratories to medical practice. Some of them, such as optical coherence tomography and photodynamic therapy, have become a common tool for clinicians while others, such as optical diffuse tomography or laser-driven acceleration for radiation therapy, are on their way from optical bench to medical instrumentation. This Special Issue presents a collection of papers based on reports delivered at the 3 biannual International Symposium “Topical Problems of Biophotonics – 2011”. The issue includes both review and research papers covering a wide range of topics varying from microscopic studies at subcellular scale to diagnostics and treatment in clinical practice. The cellular and intracellular studies are presented by four papers discussing perspective medical nanotools such as quantum dots (Loginova, p. 848, Balalaeva, p. 860) and nanodiamonds (Lin, p. 838) for imaging applications, hybrid nanocomposite films (Matteini, p. 868) aimed for treatment procedures and a paper revealing novel potential of nonlinear microscopy technique (Medyukhina, p. 878). The section on advanced laser techniques in biomedicine co-jointed with workshop on clinical biophotonics contributes four papers ranging from optical techniques in ophthalmology (Koinzer, p. 889) and mammology (Poellinger, p. 815) to laser therapy of brain injury (Huang, p. 827) and novel laser-driven sources for hadron therapy (Hofmann, p. 903). The Symposium held in July 2011 was organized by the Institute of Applied Physics of the Russian Academy of Sciences, the Nizhny Novgorod Medical Academy and the University of Nizhny Novgorod in collaboration with Gycom Ltd., Kvantron-NN Ltd., and the Government of Nizhny Novgorod Region. 227 participants from 22 countries took part in the Symposium, including scientists from Australia, Austria, Belgium, Canada, China, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, The Netherlands, Romania, Russia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, and the USA. The symposium program included four parallel topical conferences “Optical Bioimaging”, “Nanobiophotonics”, “Neuroimaging and Neurodynamics” and “Advanced Lasers in Biomedicine”, and the German-Russian workshop “Clinical Biophotonics”, thus covering a broad spectrum of topics in biophotonics. The German-Russian Workshop “Clinical Biophotonics” provided the platform for cooperation between researchers and clinicians. It was organised in cooperation with project “German-Russian Network Biotechnology” sponsored by the Federal Ministry of Education and Research, and LIFE-Center,