[Non-contact optical coherence tomography - an effective method for visualizing the exudate of the middle ear]. / Beskontaktnaya opticheskaya kogerentnaya tomografiya ­ effektivnyi metod vizualizatsii ekssudata srednego ukha.

INTRODUCTION: Otitis media with effusion (OME) accounts for 15-17% of the total number of recorded diseases of the middle ear. Surgical methods have become much more common. One of the factors affecting the tactics and effectiveness of treatment OME is the degree of viscosity of the effusion. Modern diagnostic methods do not allow to reliably identify cases of OME with high effusion viscosity. OBJECTIVE: To study the possibilities of optical coherence tomography (OCT) in the diagnosis of OME and a non-invasive study of effusion viscosity. MATERIAL AND METHODS: An analysis of the results of the examination of 29 patients who underwent surgical treatment for OME - tympanostomy. A control group of 30 patients without middle ear pathology. The study used a spectral OCT with a non-contact probe designed specifically for studies of the structural middle ear. Quantitative analysis of the results using open source ImageJ. Objectification of the degree of viscosity of the effusion was carried out by means of viscometry. A comparative analysis of the intensity of the optical signal in the external auditory canal (EAC) and in the tympanic cavity (TC) was performed, as well as a comparison of the signal from viscous and fluid effusion. RESULTS: In all patients with OME, during the OCT study, an optical signal with a higher intensity was recorded in TC than in the EAC. In all cases, in the control group in the TC, an optical signal was recorded that was identical in intensity with the signal in the EAC. When measuring the degree of viscosity of the effusion, 17 cases of OME were characterized as effusion of a low degree of viscosity, 12 cases - effusion of extreme viscosity. When comparing the average intensity of the optical signal of the OCT images of viscous and liquid effusion, a statistically significant difference was revealed, p<0.001. DISCUSSION: OCT makes it possible to detect light scattering from large scatterers - cell structures characteristic of low viscosity effusion. In addition, OCT allows you to register an optical signal from small scatterers - high molecular weight structures that are present in large quantities in viscous effusion. A correlation was found between the intensity of the optical signal in the TC and the degree of viscosity of the middle ear effusion. CONCLUSIONS: Based on OCT data, it is possible to determine the indications for surgical treatment of OME by detecting viscous exudate.

Optical coherence angiography for pre-treatment assessment and treatment monitoring following photodynamic therapy: a basal cell carcinoma patient study.

Microvascular networks of human basal cell carcinomas (BCC) and surrounding skin were assessed with optical coherence angiography (OCA) in conjunction with photodynamic therapy (PDT). OCA images were collected and analyzed in 31 lesions pre-treatment, and immediately/24 hours/3-12 months post-treatment. Pre-treatment OCA enabled differentiation between prevalent subtypes of BCC (nodular and superficial) and nodular-with-necrotic-core BCC subtypes with a diagnostic accuracy of 78%; this can facilitate more accurate biopsy reducing sampling error and better therapy regimen selection. Post-treatment OCA images at 24 hours were 98% predictive of eventual outcome. Additional findings highlight the importance of pre-treatment necrotic core, vascular metrics associated with hypertrophic scar formation, and early microvascular changes necessary in both tumorous and peri-tumorous regions to ensure treatment success.

Accurate early prediction of tumour response to PDT using optical coherence angiography.

Prediction of tumour treatment response may play a crucial role in therapy selection and optimization of its delivery parameters. Here we use optical coherence angiography (OCA) as a minimally-invasive, label-free, real-time bioimaging method to visualize normal and pathological perfused vessels and monitor treatment response following vascular-targeted photodynamic therapy (PDT). Preclinical results are reported in a convenient experimental model (CT-26 colon tumour inoculated in murine ear), enabling controlled PDT and post-treatment OCA monitoring. To accurately predict long-term treatment outcome, a robust and simple microvascular metric is proposed. It is based on perfused vessels density (PVD) at t = 24 hours post PDT, calculated for both tumour and peri-tumour regions. Histological validation in the examined experimental cohort (n = 31 animals) enabled further insight into the excellent predictive power of the derived early-response OCA microvascular metric. The results underscore the key role of peri-tumour microvasculature in determining the long-term PDT response.

[The value of optical coherence tomography and morphometry in evaluating the peripancreatic adipose tissue in infected pancreatic necrosis]. / Znachenie opticheskoi kogerentnoi tomografii i morfometrii dlia otsenki sostoianiia parapankreaticheskoi zhirovoi kletchatki pri infitsirovannom pankreonekroze.

OBJECTIVE: To investigate the morphometric and optical coherence tomography (OCT) characteristics of the microstructure of retroperitoneal peripancreatic adipose tissue during passive drainage and active perfusion-aspiration drainage for infected pancreatic necrosis. MATERIAL AND METHODS: The authors analyzed 74 samples of peripancreatic adipose tissue obtained from 37 patients with passive (Group 1) and active perfusion-aspiration drainage (Group 2) of a focus of peripancreatitis. The tissues were examined with OCT, then fixed in a formalin solution and underwent histological examination, including morphometric one. RESULTS: The examined groups showed qualitative and quantitative differences in the tissue microstructure. In Group 1 samples, the proportion (median (upper quartile; lower quartile)) of interlobular connective tissue was 5.6 (3.9; 6.1)%; and that of adipocytes was 44.6 (41.2; 51.6)%. Necrotic tissue occupied 46.2 (35.6; 56.1)% of the area of specimens. The OCT images of necrotic tissue displayed a preponderance of unstructured regions with a high signal level while the parenchymal areas showed a cellular structured pattern. In Group 2 samples, the proportion of interlobular connective tissue was 16.2 (11.4; 19.7)%, and that of adipocytes was 68.5 (59.7; 71.2)%. At the same time, Group 2 exhibited necrosis - 14.4 (11.5; 19.2%) that was 3.2 times less than in Group 1. The OCT images of Group 2 samples showed a preponderance of cellular structured regions characteristic of the parenchyma, with pronounced stromal elements, which corresponded to the histological pattern. CONCLUSION: Active perfusion-aspiration drainage of peripancreatic adipose tissue versus passive drainage is associated with a smaller proportion of necrotic tissue (14.4% versus 46.2%; p≤0.05) and a larger proportion of a stromal vascular component (16.2% vs. 5.6%; p≤0.05). OCT could qualitatively distinguish viable fat tissue parenchyma from necrotic areas, without specially preparing the samples, which was confirmed by histomorphometric results.

In-vivo longitudinal imaging of microvascular changes in irradiated oral mucosa of radiotherapy cancer patients using optical coherence tomography.

Mucositis is the limiting toxicity of radio(chemo)therapy of head and neck cancer. Diagnostics, prophylaxis and correction of this condition demand new accurate and objective approaches. Here we report on an in vivo longitudinal monitoring of the oral mucosa dynamics in 25 patients during the course of radiotherapy of oropharyngeal and nasopharyngeal cancer using multifunctional optical coherence tomography (OCT). A spectral domain OCT system with a specially-designed oral imaging probe was used. Microvasculature visualization was based on temporal speckle variations of the full complex signal evaluated by high-pass filtering of 3D data along the slow scan axis. Angiographic image quantification demonstrated an increase of the vascular density and total length of capillary-like-vessels before visual signs or clinical symptoms of mucositis occur. Especially significant microvascular changes compared to their initial levels occurred when grade two and three mucositis developed. Further, microvascular reaction was seen to be dose-level dependent. OCT monitoring in radiotherapy offers a non-invasive, convenient, label-free quantifiable structural and functional volumetric imaging method suitable for longitudinal human patient studies, furnishing fundamental radiobiological insights and potentially providing useful feedback data to enable adaptive radiotherapy (ART).

Photodynamic therapy monitoring with optical coherence angiography.

Photodynamic therapy (PDT) is a promising modern approach for cancer therapy with low normal tissue toxicity. This study was focused on a vascular-targeting Chlorine E6 mediated PDT. A new angiographic imaging approach known as M-mode-like optical coherence angiography (MML-OCA) was able to sensitively detect PDT-induced microvascular alterations in the mouse ear tumour model CT26. Histological analysis showed that the main mechanisms of vascular PDT was thrombosis of blood vessels and hemorrhage, which agrees with angiographic imaging by MML-OCA. Relationship between MML-OCA-detected early microvascular damage post PDT (within 24 hours) and tumour regression/regrowth was confirmed by histology. The advantages of MML-OCA such as direct image acquisition, fast processing, robust and affordable system opto-electronics, and label-free high contrast 3D visualization of the microvasculature suggest attractive possibilities of this method in practical clinical monitoring of cancer therapies with microvascular involvement.

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 Barrett's 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%.

[Optical coherence tomography in surgical treatment of esophageal cancer].

The authors present an analysis of possibilities of optical coherence tomography in preoperative determination of the proximal interface of the tumor. Under investigation there were 24 patients (14 of them with squamous cell carcinoma and 10 with adenocarcinoma), with localization of the process not more than 5 cm the from z-line.

[Optic coherent tomography in evaluation of the buccal mucosa status. Communication 1. Normal mucosa]. / Opticheskaia kogerentnaia tomografiia v otsenke sostoianiia slizistoi obolochki polosti rta. Soobshchenie 1. Normal'naia slizistaia obolochka.

The potentialities of optic coherent tomography (OCT) in the diagnosis of the buccal mucosa status were studied and the results are presented in two communications. Communication 1 demonstrates the tomograms of various parts of normal buccal mucosa and methods of their identification as exemplified by analysis of 1180 in vivo and 43 ex vivo OCT images. Using parallel histo-tomographic comparison, the authors distinguished the main signs of optic images, depending on the type of epithelium and characteristic features of the connective tissue stroma in various parts of the buccal mucosa. These signs are essential for understanding the optic images of the mucosa in disease, which will be shown in communication 2.

[Optic coherent tomography: a new high-resolution technology of visualization of tissue structures. Part 1. Principle of the technique. Objects of OCT applications and technical decisions for their study]. / Opticheskaia kogerentnaia tomografiia--novaia vysokorazreshaiushchaia tekhnologiia vizualizatsii struktury tkanei. Soobshchenie 1. Printsip metoda. Ob"ekty prilozheniia OKT i tekhnicheskie resheniia dlia ikh issledovaniia.

The authors present a series of three papers dedicated to studies made in Russia in the field of optic coherent tomography (OCT), the latest noninvasive high-resolution technology of visualization of the structure of biological tissues. A group of medical specialists of different disciplines has been examined over 2,000 patients for 8 years of the use of an original class of the Russian OCT devices developed at the Institute of Applied Physics, Russian Academy of Sciences, and awarded a RF State Prize in the field of science and technology in 1999. The first paper discusses the basic aspects of OCT, the objects of study, and technical decisions for the clinical application of the technique. The paper shows a place of OCT, whose resolving capacity is close to the cellular level (approximately 10-15 microns), among classical methods for imaging biological tissues. The optical images of different types of normal tissues and the method of their identification are demonstrated. It has been found that different optical properties of investing tissues and dentin permit their tomographic differentiation by showing their regular bedded structure. The tomographic pattern of investing tissues is affected by their specific features, such as the type of the lining epithelium, its keratosic processes, and the architecture of the basilar membrane.

Optical coherence tomography of the esophagus and proximal stomach in health and disease.

OBJECTIVE: Surveillance of Barrett's esophagus is problematic, as high-grade dysplasia cannot be recognized endoscopically. Endoscopic ultrasound lacks the resolution to detect high-grade dysplasia. Optical coherence tomography (OCT) employs infrared light reflectance to provide in vivo tissue images at resolution far superior to endoscopic ultrasound, nearly at the level of histology. We have developed a catheter-based system well suited for study of the GI tract. The purpose of this study was to test this catheter-based OCT system and characterize the OCT appearance of normal squamous mucosa, gastric cardia, Barrett's esophagus, and carcinoma. METHODS: The OCT catheter was passed through the operating channel of the endoscope and placed in contact with the esophageal mucosa. Image acquisition occurred in approximately 3 s. OCT images were correlated with biopsy and/or resection specimens. RESULTS: OCT was used to construct 477 images of the esophagus and stomach in 69 patients. There were unique, distinct OCT appearances of squamous mucosa, gastric cardia, Barrett's esophagus, and carcinoma. Further, these OCT images were accurately recognized by observers unaware of their site of origin. CONCLUSIONS: OCT provides a highly detailed view of the GI wall, with clear delineation of a multiple layered structure. It is able to distinguish squamous mucosa, gastric cardia, Barrett's esophagus, and cancer. This technique holds great potential as an adjunct to the surveillance of patients with Barrett's esophagus, ulcerative pancolitis, and other premalignant conditions.

In vivo endoscopic optical coherence tomography of the human gastrointestinal tract--toward optical biopsy.

BACKGROUND AND STUDY AIMS: Optical coherence tomography (OCT) is a new technique for high-resolution cross-sectional imaging using infrared light. It has over 10 times the resolution of the currently available ultrasonography. Although in vitro studies have suggested its potential for gastrointestinal imaging, in vivo studies have not been possible so far on account of technical limitations. PATIENTS AND METHODS: We describe here the first clinical study of OCT during routine endoscopy obtaining high resolution images of the normal esophageal, gastric, and colonic mucosa. Portable OCT equipment and a fiberoptic-based flexible probe for endoscopic use have been developed by the authors. RESULTS: Differences in the optical properties of epithelium, lamina propria, muscularis mucosae, and submucosa enabled distinction of the mucosal architecture. Owing to the low penetration depth (1 mm) and high resolution (10 microm), OCT images may become comparable to mucosal histological findings. Image acquisition time was 1.5 seconds, and the entire procedure was completed within 5 minutes. Endoscopic OCT images of colonic adenoma and carcinoma were also studied and compared with the corresponding histology. CONCLUSIONS: The newly developed portable OCT equipment and flexible fiberoptic probe makes OCT a promising method for endoscopic "optical biopsy".

In vivo endoscopic optical coherence tomography of esophagitis, Barrett's esophagus, and adenocarcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: We studied the feasibility of endoscopic optical coherence tomography imaging in esophageal disorders, including Barrett's esophagus and Barrett-related adenocarcinoma. Optical coherence tomography is a high-resolution cross-sectional imaging technique with a resolution of almost 10 microm. PATIENTS AND METHODS: The mucosal architecture of reflux esophagitis (n = 9) and Barrett's esophagus (n = 9) including Barrett-related esophageal cancer (n = 6) was studied by optical coherence tomography imaging. RESULTS: In different stages of reflux esophagitis edema, fibrinoid deposits, or loss of the epithelial layer were observed. Optical coherence tomography images of Barrett's esophagus substantially differed from normal esophagus, reflux esophagitis, and esophageal carcinoma. A stratified structure of the mucosa was still preserved in Barrett's esophagus. However, images of Barrett-related cancer lacked the regular structure of the esophagus. CONCLUSIONS: The high consistency of the first optical coherence tomography findings, the resolution of up to 10 microm, and the distinct pattern of normal, inflammatory, premalignant and malignant tissues make optical coherence tomography a promising method for endoscopically obtained optical biopsy.

In vivo optical coherence tomography imaging of human skin: norm and pathology.

BACKGROUND/AIMS: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies. METHODS: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5-2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in-depth resolution limited by the spectral bandwidth (40-50 nm) of the probing light was approximately 20 &mgr;m. The lateral resolution determined by the probe light focusing ranged from 15 to 30 &mgr;m. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2-6 mm long took 2-4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients. RESULTS: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT. CONCLUSIONS: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15-20 &mgr;m, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5-2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.

In vivo detection of experimentally induced cortical dysgenesis in the adult rat neocortex using optical coherence tomography.

Imaging cerebral structure in vivo can be accomplished by many methods, including MRI, ultrasound, and computed tomography. Each offers advantages and disadvantages with respect to the others, but all are limited in spatial resolution to millimeter-scale features when used in routine applications. Optical coherence tomography (OCT) is a new, high resolution imaging technique which uses light to directly image living tissue. Here, we investigate the potential use of OCT for structural imaging of the fully developed mammalian cerebral cortex. In particular, we show that OCT can perform in vivo detection of neocortex and differentiate normal and abnormal cortical anatomy. We present the results of detailed optical coherence tomographic (OCT) observations of both normal and abnormal rat neocortex obtained in vivo. Comparative histologic analysis shows excellent correlation with the OCT tomograms.

In vivo OCT imaging of hard and soft tissue of the oral cavity.

We use optical coherence tomography (OCT) to perform a comprehensive program of in vivo and in vitro structural imaging of hard and soft tissues within the oral cavity. We have imaged the different types of healthy oral mucosa as well as normal and abnormal tooth structure. OCT is able to differentiate between the various types of keratinized and non-keratinized mucosa with high resolution. OCT is also able to provide detailed structural information on clinical abnormalities (caries and non-caries lesions) in teeth and provide guidance in dental restorative procedures. Our investigations demonstrate the utility of OCT as a diagnostic imaging modality in clinical and research dentistry.

Endoscopic applications of optical coherence tomography.

We report results of application of our endoscopic optical coherence tomography (EOCT) system in clinical experiments to image human internal organs. Based on the experience of studying more than 100 patients, we make first general conclusions on the place and capabilities of this method in diagnosing human mucous membranes. It is demonstrated that EOCT can serve for several clinical purposes such as performing directed biopsy, monitoring functional states of human body, guiding surgical and other treatments and monitoring post-operative recovery processes. We show that applications of OCT are more informative in the case of internal organs covered by epithelium separated from underlying stroma by a smooth basal membrane and therefore concentrate on the results of the EOCT study of three internal organs, namely of larynx, bladder, and uterine cervix. Finally, we report first examination of internal organs in abdomen with the use of laparoscopic OCT.

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.