Natalia D. Gladkova

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.

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.

Melanin effect on light scattering in tissues: from electrodynamics of living cells to OCT imaging

In this report we present the results on optical coherence tomography (OCT) imaging of human skin with pigmented lesions and compare these results with the postexperimental histological analysis. We demonstrate that beside the proposed limitation of the image depth due to a strong absorption of the probing radiation, the melanin-containing layers of tissues are characterized by an increased backscatter. It is especially interesting to note that after a proper contrasting of OCT pictures, fine spatial distributions in the scattering cell conglomerations become distinguishable. As an example we show the case of the border-line nevus where, in accordance with the histological data, we have succeeded in localizing a melanin containing cell distribution over the all basal membrane on the in vivo recorded tomographs. The peculiarities of the studied OCT images can be explained by characteristics of light scattering by a single living cell. We have performed a computer simulation of electromagnetic wave propagation in a single cell using the full set of the Maxwell equations with known dielectric constants for various intracellular components. A particular result of this modeling is that due to a noticeable difference in dielectric constants between the cytoplasm and the melanin granules, a substantial increase of the cell backscattering cross-section takes place.

Optical coherence tomography in the diagnosis of dysplasia and adenocarcinoma in Barret's esophagus

Statistical analysis of endoscopic optical coherence tomography (EOCT) surveillance of 78 patients with Barretts esophagus (BE) is presented in this study. The sensitivity of OCT device in retrospective open detection of early malignancy (including high grade dysplasia and intramucosal adenocarcinoma (IMAC)) was 75%, specificity 82%, diagnostic accuracy - 80%, positive predictive value- 60%, negative predictive value- 87%. In the open recognition of IMAC sensitivity was 81% and specificity were 85% each. Results of a blind recognition with the same material were similar: sensitivity - 77%, specificity 85%, diagnostic accuracy - 82%, positive predictive value- 70%, negative predictive value- 87%. As the endoscopic detection of early malignancy is problematic, OCT holds great promise in enhancing the diagnostic capability of clinical GI endoscopy.

In-vivo optical coherent tomography of teeth and oral mucosa

Our investigations have been devoted to OCT capabilities in imaging normal and diseased tooth structures and different types of oral mucosa. OCT tomograms distinctly exhibit the structural elements of oral mucosa. Depending on localization and keratinization, different types of mucosa are also seen in OCT images. OCT images of those parts where epithelium evidences high keratinization substantially differ from images of those parts where epithelium evidences low or no keratinization in its normal state. OCT imaging allows one to clearly differentiate between caries and noncaries lesions, which is very important in practical dentistry. OCT has made it possible to quite accurately diagnose a fissure caries in the early stage that has been unreliable with an X- ray examination. The OCT technique is capable of dynamic monitoring the restorative process. It also allows in vivo examination of fillings as well as the state of surrounding tissues. It is possible to detect filling defects caused by an incorrect filling procedure either during the process of restoration of some time later. The results of our investigations suggest that OCT is a potentially useful modality for clinical and research dentistry.

New advances in optical coherence tomography for diagnostics of cervical neoplasia

Diagnostic value of standard OCT for recognizing cervical neoplasia has been evaluated: sensitivity is 82%, specificity is 78%, and diagnostics accuracy is 81%. To increase it several approaches have been suggested: application of hyperosmotic agents, cross-polarization tomography, complementary use of fluorescence spectroscopy and OCT, additional computer processing of the OCT-images and optical coherence microscipy.

Clinical study of bladder diseases using optical coherence tomography

Optical Coherence Tomography (OCT), a new optical bioimaging technique was used to evaluate the state of mucosa in the urinary bladder. The state of mucosa of the bladder was evaluated in patients with prostatic adenoma (11 male patients) during the course of prostatectomy operation via a resection cytoscope. An OCT probe was inserted into the biopsy channel of a cystoscope. The sites to be imaged by OCT were determined visually and, after OCT study, underwent excisional biopsy and subsequent histological examination. Children (9 girls) were examined during diagnostic cystoscopy. Our analysis of diagnostic capabilities of OCT in urology relies on the comparison of OCT information on normal and morphologically altered tissues. OCT is able to provide objective data concerning the structure of mucosa of the bladder due to the difference in optical properties of different layers in tissue. The epithelium and the layers of connective tissue, both in norm and pathology, are clearly visualized in the tomograms. Our OCT study of healthy mucosa of the urinary bladder has demonstrated that the epithelium appears in the tomograms as an upper highly backscattering layer. An underlying optically less transparent layer, much greater in size than the previous one, corresponds to the connective tissue of the mucosa. Inside this layer, elongated poorly backscattering formations with clear contours are seen; they do not alter the longitudinal structure of the submucosal layer. These formations are blood vessels. Optical patterns characteristic of chronic inflammation are obtained. They correspond, as confirmed histologically, to liquid accumulation, cellular infiltration of mucosal layers, hypervascularization, and fibrosis. OCT information on proliferative processes, such as papillomatosis of the urinary bladder and squamous cell carcinoma, is analyzed. It is shown that OCT can reliably reveal edema of the mucous membrane of the bladder and identify the character of appearing elements, such bulla, granule and polyp. OCT can provide information on the structure of tissue by characterizing its thickness and scattering properties.

Optical coherence tomography in diagnosing cervical cancer

Cervical cancer remains one of the most significant problem in oncogynecology. It tends towards treatment approaches that provide termination of pathological processes along with preservation of the patients life quality. There is a need in earlier and more accurate diagnosis of pathological states, objective assessment of physiological processes, and adequate monitoring of the course of treatment. In our previous publications we have reported unique capabilities of the Optical Coherence Tomography (OCT) to image in vivo the mucosa structure of the cervix and to monitor various physiological and pathological alterations. In this report, we present results of OCT application to diagnose different stages of cervical cancer and to control its treatment at early stages. We have performed OCT-colposcopy in 11 female patients with cervical cancer to derive OCT criteria of this disease, to provide exact demarcation of a pathological area, and to determine a real size of a tumor. We have found that, in general, borders of a tumor, defined visually and detected with OCT by violation of the basement membrane in exocervix, do not coincide. The mismatch depends on a stage of cancer and can be as much as several millimeters. This information is especially important for evaluation of linear dimension of tumors with 3 - 5 mm invasion and also for differential diagnosis between the T1 and T2 stages with cancer extension onto vagina.

Capabilities of OCT in diagnosing pathological processes, functional states, and treatment adequacy in gynecology

We report on the results of using the optical coherence tomography (OCT) as one of the diagnostic methods at the Department of Gynecology of the Nizhny Novgorod Regional Hospital. An endoscopic OCT device adjusted for gynecological examinations with colposcopy, hysteroscopy and laparoscopy has been developed at the Institute of Applied Physics. It provides clinicians with sharp (up to 15 - 20 micron resolution) images of 1.5 mm thick superficial mucosa layers in the female genital tract, that are recorded at the 0.83 micron wavelength with approximately 1 frame/second rate for a 200 X 200 pixel image. Data obtained during examination of more than 100 patients demonstrate the capability of OCT in estimation of structural alterations in organs, connected with different types of pathologies and functional states of the female genital system. We present first results of OCT application to assess the adequacy of cervical pathologies treatment (electro-, laser surgery and cryotherapy) and to control the healing process.