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.

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 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.