Felix I. Feldchtein

In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa

First results of endoscopic applications of optical coherence tomography for in vivo studies of human mucosa in respiratory, gastrointestinal, urinary and genital tracts are presented. A novel endoscopic OCT (EOCT) system has been created that is based on the integration of a sampling arm of an all-optical-fiber interferometer into standard endoscopic devices using their biopsy channel to transmit low-coherence radiation to investigated tissue. We have studied mucous membranes of esophagus, larynx, stomach, urinary bladder, uterine cervix and body as typical localization for carcinomatous processes. Images of tumor tissues versus healthy tissues have been recorded and analyzed. Violations of well-defined stratified healthy mucosa structure in cancered tissue are distinctly seen by EOCT, thus making this technique promising for early diagnosis of tumors and precise guiding of excisional biopsy.

In vivo optical coherence tomography feasibility for bladder disease

PURPOSE Optical coherence tomography is a new imaging modality capable of imaging luminal surface of biological tissue in the near infrared range with a spatial resolution close to the cellular level. We identified characteristic optical coherence tomography patterns for nonproliferative and proliferative inflammation, and malignant alterations of the bladder. MATERIALS AND METHODS Optical coherence tomography was performed to image the bladder of 66 patients. The probe passed through the operating channel of a cystoscope and was pressed onto the mucosal site of interest. A mucosal biopsy of the image site was obtained. Optical coherence tomography was used to construct 680 images of the bladder and the images were compared with histology slides. RESULTS Optical coherence tomography images of normal bladder showed 3 layers, namely the mucosa or transitional epithelium, submucosa and smooth muscle. In exudative processes there were poor light scattering areas in the connective tissue layer. Images of bladders with proliferative cystitis revealed nonuniform thickening of the epithelium or hyperplasia. Squamous metaplasia appeared as thicker and less transparent epithelium with a jagged boundary. Images of transitional cell carcinoma were characterized by the complete loss of a regular layered structure of the bladder wall and the penetration depth of optical imaging was slight. CONCLUSIONS This study provides the characteristic optical coherence tomography pattern of nonproliferative and proliferative inflammation, and the characteristic appearance of severe dysplasia and transitional cell carcinoma. This technique may be useful as a guide for biopsy and for assisting in establishing resection margins.

Differential diagnosis of human bladder mucosa pathologies in vivo with cross-polarization optical coherence tomography

Quantitative image analysis and parameter extraction using a specific implementation of polarization-sensitive optical coherence tomography (OCT) provides differential diagnosis of mucosal pathologies in in-vivo human bladders. We introduce a cross-polarization (CP) OCT image metric called Integral Depolarization Factor (IDF) to enable automatic diagnosis of bladder conditions (assessment the functional state of collagen fibers). IDF-based diagnostic accuracy of identification of the severe fibrosis of normal bladder mucosa is 79%; recurrence of carcinoma on the post-operative scar is 97%; and differentiation between neoplasia and acute inflammation is 75%. The promising potential of CP OCT combined with image analysis in human urology is thus demonstrated in vivo.

In vivo optical coherence tomography of human skin microstructure

A compact effective optical coherence tomography (OCT) system is presented. It contains approximately equals 0.3 mW superluminescent diode with spectral width 30 nm FWHM (providing approximately equals 15 micrometers longitudinal resolution) and fiber interferometer with integrated longitudinal scanning. The dynamic range 60 dB allows to observe structure of human skin in vivo up to 1.5 mm in depth. A comparison of obtained tomographs with data of histologic analysis of the same samples of the skin have been carried out to identify the observed structures and determine their optical properties. This technique allows one to perform noncontact, noninvasive diagnostic of early stages of different pathological state of the skin, to measure the burn depth and to observe the process of the recovery. Unlike scanning confocal microscopy, OCT is more suitable for an endoscopic investigation of the mucous membranes of hollow organs. Possible diagnostic applications include dermatology, gastroenterology, gynecology, urology, oncology, othorinolaryngology, transplantology. The most promising features are the potential possibility of differential diagnosis of precancer and various types of cancer, estimation of the invasion depth, differential diagnosis of inflammation and dystrophic processes, control of radical operative treatment.

Evaluation of oral mucosa collagen condition with cross-polarization optical coherence tomography

The goal of the research was analysis of the effect of collagen condition in formation of cross-polarized CP OCT images. We used of the CP OCT technique for studying collagen condition on an example of oral mucosa. Special histologic picrosirius red (PSR) staining of cheek mucosa specimens was used with subsequent assessing of the result of collagen staining in polarized light. High correlation (r = 0.692, p = 0.0001) between OCT signal standard deviation (SD) in cross-polarized images and brightness of PSR stained collagen fibers in cheek mucosa specimens was demonstrated in patients with inflammatory intestine and oral mucosa diseases. We have found that the OCT signal SD in cross-polarized images reflects two boundary conditions of collagen disorganization, namely, loss of fiber properties at active inflammation which attenuates the signal and fibrosis that occurs due to synthesis of a new remodeled collagen which amplifies the OCT signal.

Monitoring and animation of laser ablation process in cataracted eye lens using coherence tomography

Optical coherent tomography (OCT) enables one to follow the pulse-to-pulse kinetics of laser interactions with turbid biological tissues. In experiments we investigate the effect of free running mid infrared laser radiation of different wavelengths on a cataract-suffered human lens in vitro. Different regimes of laser ablation and preablation surface transformations are monitored in situ.

Optical coherence tomography using tissue clearing for skin disease diagnosis

Capabilities of optical coherence tomography (OCT) as well as OCT enhanced by tissue clearing using glycerol solution for differential diagnosis of erythematoses, bullous and papulous skin diseases are demonstrated on 118 patients sample. It is shown that high-skilled dermatologists familiar with fundamentals of skin pathomorphology but without previous experience in OCT studies and interpretation of optical features are capable, when using OCT, of distinguishing optical images of various skin diseases to a high diagnostic accuracy (ranging from 76% to 94%) and with good multirater interobserver agreement between different specialists (kappa up to 0.69). Application of glycerol improves contrast and penetration depth of OCT images of skin significantly, thus reliably improving diagnostic validity of the technique and facilitating differential diagnosis of clinically similar dermatoses accompanied by papulous eruption.

Capabilities of optical coherence tomography in laryngology

We present first result of using the optical coherence tomography (OCT) in complex clinical studies in laryngology. Mucosa of the upper and middle portions of larynx is of special interest for OCT applications: it is clinically important, easily accessed by an endoscopic OCT probe, and possesses a well defined and rich tomographic structure. We have examined several tens of patients with abnormalities in vocal folds. The diagnosis was made based on clinical data including laryngoscopy and finally confirmed morphologically. When examining larynx mucosa, an endoscopic OCT probe has been introduced through a standard laryngoscope lumen, so that OCT imaging has been performed in parallel with visual observation. The OCT studies have demonstrated that in comparison with stratified healthy mucosa, carcinomatous regions have no tomographically differentiated structure, thus allowing one to exactly define the border of a tumor. Vocal nodules are imaged as poorly scattering regions without clear boundaries under preserved epithelium. Cysts of gland mucosa are seen with OCT as sharply delineated shadows at the depth of several hundred micrometers. We have also examined several patients with carcinoma after a course of radiation therapy and observed different changes in OCT images of adjoining epithelium corresponding to metaplasia, hyperplasia, and sclerosis.

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.

Kinetics of water transfer and stress relaxation in cartilage heated with 1.56 μm fiber laser

In this work we have used for the first time 1.56 micrometer fiber laser to study mechanisms of IR laser induced stress relaxation in cartilage. We have applied several in-situ monitoring techniques: local temperature measurements (IR radiometry and thermocouple), IR-light absorption, direct stress measurements, micro-balancing, visible light scattering and optical coherent tomography. We have measured temporal behavior of 1.56 micrometer laser light transmission through the cartilage sample at different intensities with synchronous temperature and stress monitoring. The observed bleaching effect (self-induced transparency) is caused by water release from irradiating zone, water evaporation from the cartilage surface and, also, by temperature shift and decrease of intensity of water absorption bands.