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.

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.

Optical coherence tomography as a diagnostic aid to visual inspection and colposcopy for preinvasive and invasive cancer of the uterine cervix.

The purpose of this study was to determine the sensitivity and specificity of optical coherence tomography (OCT) under two well-defined clinical settings. First, as an aid to cervical cancer screening, using visual inspection with acetic acid (VIA) in low-resource settings, and the second, as an adjunct to the traditional management of abnormal cervical cytology with colposcopy and biopsy. Patients referred for colposcopy with > or = atypical squamous cells of undetermined significance were accrued for the study. Each subject underwent VIA and colposcopy. OCT was performed in all VIA- and colposcopy-positive areas and at the squamocolumnar junction in all four quadrants. The sensitivity of VIA for > or = cervical intraepithelial neoplasia 2 was 76% (95% CI 58-88). When OCT was applied to VIA as a secondary screen, the specificity improved from 34% (95% CI 27-41) to 61% (95% CI 60-74). With liberal diagnostic criteria for the majority of the colposcopy examinations, OCT showed an even greater relative improvement in specificity. OCT proved to be a fair diagnostic modality (receiver operating characteristic curve 0.73) adjunctive to VIA and colposcopy. On the basis of the above findings, we believe that this technology could potentially show greatest utility in the management of cervical dysplasia in low-resource settings where a single episode of care is most desirable.

Diagnostic efficacy of optical coherence tomography in the management of preinvasive and invasive cancer of uterine cervix and vulva.

The purpose of this study was to understand the capabilities and utility of optical coherence tomography (OCT) in characterizing tissue in patients with precancer and cancer of the uterine cervix and vulva. OCT is an optical technique that uses low-coherence interferometer to develop a two-dimensional image of optical scattering from internal tissue microstructure. This study was designed to develop diagnostic criteria. Women undergoing colposcopic evaluation secondary to an abnormal Papanicolaou smear or visualized grossly abnormal vulvar lesion comprised the study population. Under colposcopic visualization, the OCT device was applied to normal regions in all patients and abnormal areas when present, and images were captured. Each subject then underwent multiple directed biopsies. Images were then reviewed and compared with matched histology. A total of 50 women were recruited for the study. Of the 50 patients evaluated, 18 had cervical intraepithelial neoplasia (CIN) II,III, 14 had CIN I, 13 had metaplasia/inflammation, two had invasive squamous cell carcinoma of the cervix, and three had a diagnosis of Paget's disease of the vulva. Analysis of the OCT images showed a repetitive pattern that represented normal squamous epithelium of the cervix in 100% of the normal biopsies. Images of the 18 patients with histologically proven CIN II,III showed an unstructured homogeneous highly backscattering region with fast attenuation of the signal in 16 (89%) of the patients. OCT is a new approach for the early identification of cervix and vulvar malignancies. Using information inherent to the returning photon signals from tissue, early morphological and light-scattering changes can be detected during tumorigenesis. It has the potential to be a true optical biopsy. If diagnostically comparable to a biopsy, then clearly the ability of OCT to provide a point of service diagnosis would serve a significant advantage.

First in vivo optical coherence tomography in the human bile duct.

BACKGROUND AND STUDY AIMS: Optical coherence tomography (OCT) is a novel technique for performing high-resolution, cross-sectional tomographic imaging in human tissue, which allows resolution of up to 10 microm. The short depth of penetration allows assessment of the superficial 2 mm of the gastrointestinal tract, an area that is difficult to appraise even with high-frequency ultrasound. This is the first report on in vivo OCT of the human biliary system. The aim was to assess the feasibility of the technique. PATIENTS AND METHODS: Four cases of intraductal OCT are presented. The probe was inserted through the working channel of a duodenoscope. RESULTS: The connective tissue layer and the underlying retroperitoneal tissue, with less backscattering, could be clearly demonstrated. The images showed a layer architecture which was similar to that found histologically. CONCLUSIONS: OCT of the biliary system is feasible in patients with biliary pathology. Interpretable images were obtained, and clinical use needs further assessment. As current OCT probes and processors do not yet provide optimal resolution, further generations of equipment with improved image quality are required.

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.

Optical coherence tomography monitoring for laser surgery of laryngeal carcinoma.

BACKGROUND AND OBJECTIVES: The goal of this study is to apply a new bioimaging modality, the Optical Coherence Tomography (OCT), for intraoperative control in laser surgery of laryngeal carcinoma. STUDY DESIGN/MATERIALS AND METHODS: We studied 26 patients with laryngeal carcinoma in situ and in T(1), T(2) stage. We used an endoscopic OCT device for imaging at a wavelength of 0.83 microm with the acquisition rate of approximately 0.5 frames/s for a single (200 x 200 pixel) tomogram. All patients were operated with a surgical YAG:Nd laser at two switchable wavelengths of 1.44 microm and 1.32 microm by laryngofissure, direct microlaryngoscopy, and fibrolaryngoscopy. RESULTS: Information on structural alterations in laryngeal mucosa to the depth of 2 mm, obtained by OCT, makes it possible to precisely locate tumor borders, thus giving an opportunity to control the surgical treatment of laryngeal carcinoma. The YAG:Nd laser scalpel with wavelengths of 1.32 microm and 1.44 microm is successful in surgical procedures both in open and closed larynx due to efficient coagulation and minimization of collateral tissue damage area. Combination of the two wavelengths in the single laser unit and intraoperative OCT monitoring result is a new modality for minimally invasive larynx surgery. CONCLUSIONS: OCT is promising to become a new diagnosing method of laryngeal carcinoma and a tool for laser treatment monitoring.

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 situ Monitoring of Laser Modification Process in Human Cataractous Lens and Porcine Cornea Using Coherence Tomography.

We demonstrate that optical coherence tomography (OCT) is a convenient diagnostic tool to monitor pulse-to-pulse kinetics in laser interactions with biological tissue. In experiments on laser modification and ablation of the cataractous human lens and the porcine cornea we have applied this technique in situ to investigate different modes of preablation tissue swelling, crater formation and thermally affected zone development. The cataractous lens is an example of highly scattering media whereas the cornea is initially low scattering. The radiation with different wavelengths has been employed including that of a YAG:Er laser (λ=2.94 µm), a glass:Er laser (λ=1.54 µm), YAG:Nd lasers (λ=1.32 µm and λ=1.44 µm), as well as of the fifth harmonic of a Nd:YAP laser (λ=0.216 µm). Pulse-to-pulse OCT monitoring has been accompanied by the probe beam shielding diagnostics to provide the time-resolved observation of the interaction dynamics. © 1999 Society of Photo-Optical Instrumentation Engineers.

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.