Optical coherence tomography imaging of bullous diseases

In recent years, optical coherence tomography (OCT) became gained importance in medical disciplines like ophthalmology, due to its noninvasive optical imaging technique with micrometer resolution and short measurement time. It enables e. g. the measurement and visualization of the depth structure of the retina. In other medical disciplines like dermatology, histopathological analysis is still the gold standard for skin cancer diagnosis. The EU-funded project VIAMOS (Vertically Integrated Array-type Mirau-based OCT System) proposes a new type of OCT system combined with micro-technologies to provide a hand-held, low-cost and miniaturized OCT system. The concept is a combination of full-field and full-range swept-source OCT (SS-OCT) detection in a multi-channel sensor based on a micro-optical Mirau-interferometer array, which is fabricated by means of wafer fabrication. This paper presents the study of an experimental proof-of-concept OCT system as a one-channel sensor with bulk optics. This sensor is a Linnik-interferometer type with similar optical parameters as the Mirau-interferometer array. A commercial wavelength tunable light source with a center wavelength at 845nm and 50nm spectral bandwidth is used with a camera for parallel OCT A-Scan detection. In addition, the reference microscope objective lens of the Linnik-interferometer is mounted on a piezo-actuated phase-shifter. Phase-shifting interferometry (PSI) techniques are applied for resolving the conjugate complex artifact and consequently contribute to an increase of image quality and depth range. A suppression ratio of the complex conjugate term of 36 dB is shown and a system sensitivity greater than 96 dB could be measured.

Microaneurysms (MAs) are pathognomonic signs that help clinicians to detect diabetic retinopathy (DR) in the early stages. Automatic detection of MA in retinal images is an active area of research due to its application in screening processes for DR which is one of the main reasons of blindness amongst the working-age population. The focus of these works is on the automatic detection of MAs in en face retinal images like fundus color and Fluorescein Angiography (FA). On the other hand, detection of MAs from Optical Coherence Tomography (OCT) images has 2 main advantages: first, OCT is a non-invasive imaging technique that does not require injection, therefore is safer. Secondly, because of the proven application of OCT in detection of Age-Related Macular Degeneration, Diabetic Macular Edema, and normal cases, thanks to detecting MAs in OCT, extensive information is obtained by using this imaging technique. In this research, the concentration is on the diagnosis of MAs using deep learning in the OCT images which represent in-depth structure of retinal layers. To this end, OCT B-scans should be divided into strips and MA patterns should be searched in the resulted strips. Since we need a dataset comprising OCT image strips with suitable labels and such large labelled datasets are not yet available, we have created it. For this purpose, an exact registration method is utilized to align OCT images with FA photographs. Then, with the help of corresponding FA images, OCT image strips are created from OCT B-scans in four labels, namely MA, normal, abnormal, and vessel. Once the dataset of image strips is prepared, a stacked generalization (stacking) ensemble of four fine-tuned, pre-trained convolutional neural networks is trained to classify the strips of OCT images into the mentioned classes. FA images are used once to create OCT strips for training process and they are no longer needed for subsequent steps. Once the stacking ensemble model is obtained, it will be used to classify the OCT strips in the test process. The results demonstrate that the proposed framework classifies overall OCT image strips and OCT strips containing MAs with accuracy scores of 0.982 and 0.987, respectively.

Background: Optical coherence tomography (OCT) is a non-invasive optical imaging technique providing high-resolution images. OCT may be useful as a monitoring tool during treatment of actinic keratoses (AK) and skin cancer. Objective: To examine and describe how OCT skin morphology changes when the tissue is exposed to the effects of cryotherapy. Methods: Normal ex vivo skin and in vivo AK lesions were examined. Cryotherapy was applied and OCT images were acquired at defined time points. OCT morphology was described. Results: Cryotherapy treatment produced an opaque iceball, and freezing depth could not be monitored by OCT. Vesicle formation after cryotherapy could be identified in OCT images. In ex vivo skin no vesicle formation occurred. Conclusion: OCT cannot monitor the freezing depth, but OCT was able to visualise AK lesions and vesicle formation shortly after cryotherapy. Results add to the assumption that OCT could be used in monitoring non-invasive treatments.

High-Definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-Resolution Optical Coherence Tomography

Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue birefringence. No evidence of differences in OCT or PS-OCT images were detected between specimens of similar structural characteristics where proteoglycan was judged present or absent by safranin-O Fast Green staining. The combined use of OCT and PS-OCT technologies to obtain images from a single system is able to demonstrate and discriminate between characteristics of very early stages of surface irregularities not previously reported for OCT imaging, to deep clefts and collagen matrix disorganization for tissue at depths of up to 2 mm with good correlation to histology. PS-OCT and accumulated optical phase retardation images of articular cartilage as constructed from alterations in Stokes vector parameters appear to give a valuable but different assessment of alterations in tissue birefringence and organization than have been reported for OCT images obtained with the use of polarized or non-polarized light sources. This is the first time that alterations in the polarization state of light reflected from within the tissue have been demonstrated to be consistent with changes observed in the orientation and organization of the collagen matrix in advanced stages of DJD. The degree of phase transformation of light reflected from within the tissue as determined by PS-OCT imaging does not appear to be altered by the presence or absence of proteoglycan.

To investigate morphological variations in the macular area with optical coherence tomography (OCT) after vitrectomy for diabetic fibrovascular proliferation. We reviewed 108 cases using OCT 7-15 months after vitrectomy. Of these, 32 received OCT within 3 months postoperatively. Morphological variations were categorized and correlated with visual outcome. Only 24 cases (21.4%) had no obvious abnormalities. The most frequent findings were epiretinal membrane (52.8%), macular thickening (37.0%) and macular cysts (28.7%). Multivariate regression showed that diffuse macular thickening, loss of foveal depression and diffuse retinal thinning were significantly associated with poor visual acuity. Sequential OCT (< 3 and >or= 7 months) revealed that epiretinal membrane and oedema outside of fovea changed significantly between two examinations. OCT may identify diverse morphological changes in the macular area after diabetic vitrectomy for fibrovascular proliferation. Macular appearance may change over time, and certain types of morphological changes may be associated with poor visual function.

Age-related macular degeneration (ARMD) is a degenerative eye disease among people over the age of 50. This disorder affects the retina and macula of the eye. The macula is the central part of the retina. The function of the macular region is to give a sharp and clear vision. ARMD is mainly identified by the presence of yellow deposits called drusen and the structural changes in the retinal pigment epithelium (RPE) layer of the retina. If ARMD is not identified at an early stage, it will lead to permanent blindness. The ARMD is mainly diagnosed using Color fundus and Optical coherence tomography (OCT) images of the retina. OCT is an imaging technique that makes use of low-coherence light to capture two-and three-dimensional images from within optical scattering media. OCT images usually are at a micrometer resolution, affected by a noise called speckle noise. If speckle noise is present in an OCT image, diagnosis of ARMD is very difficult, irrespective of whether it is manually or automatically. So, removal of speckle-noise is significant for the accurate diagnosis and early detection of ARMD. In this paper, we evaluate the performance of eight popular image noise reduction filters for its ability to remove speckle noise in terms of different performance measures on a publicly available OCT dataset. Our evaluation shows that, out of the filters selected for assessment, a fast non-local mean filter outperforms all other filters regarding all the performance measures used.

Diagnosis of bullous pemphigoid (BP) and pemphigus is based on clinical features, histology, immunofluorescence and laboratory data. To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions. This was an observational, retrospective, multicentre study in which patients with suspicious lesions for BP or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations from January 2014 to December 2015. A total of 72 lesions in 24 selected patients were evaluated. Additionally, apparently unaffected skin at two different distances [near (1-2 cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion detectability. RCM was able to detect subepidermal and intra-epidermal blisters, respectively, in 75% and 50% of the patients affected by BP and pemphigus. At OCT, the exact blister level was identified in all patients. Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin deposition inside the blisters was only found in BP, evidenced both at RCM and OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%) clinically healthy skin, while among patients with pemphigus were observed in 10 (20.8%) apparently unaffected skin. RCM and/or OCT provide useful information for a rapid diagnosis of BP and pemphigus and for the identification of biopsy site. Combined use of RCM and OCT is optimal because associates the higher resolution of RCM with the greater penetration depth of OCT. OCT could be an optimal tool for treatment monitoring, especially in the cases of subclinical lesions. However, histopathologic and immunologic examinations remain the gold standard for establishing the final diagnosis.

Blood flow during early embryonic development modulates the growth and remodeling (volume and shape) of the heart. Several studies in animals have shown that altered hemodynamic conditions during embryonic development resulted in cardiac defects resembling those in the 1% of human newborns with congenital heart disease. To better understand the relationship between blood flow and cardiac development, as well as the mechanisms by which blood flow affects heart growth, we must quantify intracardiac blood-flow velocities during early embryonic development. There are, however, two main challenges in measuring blood-flow dynamics in the developing heart. The heart is tiny (<1mm) and it beats fast ( 2Hz). Both limit the accuracy of obtaining blood-flow velocities. To overcome that difficulty, we combined computational modeling and imaging in vivo. We used a chicken embryo and optical coherence tomography (OCT) to image the beating, developing heart. During early development, the hearts of humans and chickens are very similar. The chick embryo and its heart are easy to access after opening the egg shell. OCT is a noninvasive optical-imaging technique that allows us to look at tissue sections in vivo with micrometer precision. Moreover, our OCT system simultaneously acquires structural (morphological) andDoppler (velocity) images, which allow measurements of both cardiac geometry and blood-flow velocity during the beating cycle (see Figure 1). Images of the outflow tract (OFT) of the developing chick heart at Hamburger-Hamilton (HH) stage 18 ( 3 out of 21 days of incubation) reveal a complex interaction between blood-flow dynamics and the heart’s beating motion.1, 2 To handle the imaging-speed limitations of our OCT system in picturing rapidly changing 3D cardiac geometry over the beating cycle, we developed a synchronization procedure that allows reconstruction of a 4D image of the heart (3D cardiac Figure 1. Simultaneous structural (top) and Doppler (bottom) optical coherence tomography (OCT) images of the cardiac outflow tract (OFT) of a chick embryo showing (A) lateral and (B) cross-sectional views when the OFT walls are expanded.

Three-Dimensional Optical Coherence Tomography on Endoscopic Mucosal Resection Specimens Confirms Identification of Malignant From Metaplastic Lesions in Patients With Barrett's Esophagus

Retinal drawings are a valuable tool allowing for easy visual communication of ophthalmoscopic findings despite less frequent use today in the era of digital medical records and abundance of imaging options (Schachat et al. 2018). For rhegmatogenous retinal detachments (RRD), drawings of retinal breaks and degree of detachment can aid patient management. In a RRD with an intact fovea, the distance of a detachment from the fovea indicates the distance that ensures central visual acuity, as fovea-off RRD are at risk of a worse visual outcome (Salicone et al. 2006; Hajari et al. 2014; Rezar et al. 2016). Communicating the distance from the RRD border to the fovea to the patient as well as other healthcare personnel can likely improve outcomes especially since patient movement has shown to cause retinal detachment progression (de Jong et al. 2017). This study examines the subjective/objective discrepancy or whether the degree of detachment is communicated accurately by comparing the user-dependent slit-lamp and/or indirect ophthalmoscopy findings to optical coherence tomography (OCT) images taken immediately after diagnosis. For this study, we solely view the degree of detachment as distance from the RRD border to the fovea. Retinal drawings were obtained from fovea-on RRD patients participating in a prospective study (ClinicalTrials.gov Identifier: NCT03655652) at the Department of Ophthalmology, at Rigshospitalet – Glostrup, Denmark. The retinal drawings were either drawn digitally or on paper by ophthalmology residents. The shortest distance from the retinal detachment border on a drawing to the fovea was measured with Fiji imagej software (v. 1.52 g) (https://fiji.sc). For each retinal drawing, we measured the corresponding distance on OCT images (Heidelberg Spectralis, Heidelberg Engineering, Heidelberg, Germany) taken immediately after examination and retinal drawing. The shortest distance on OCT between fovea and the RRD border was measured with built-in software (heidelberg eye explorer, v. 1.9.10.0, Heidelberg Engineering, Heidelberg, Germany). Patients with an RRD > 10 mm from the fovea were excluded as our digital template for retinal drawings only allows the RRD border to be within 10 mm of the fovea. r (v. 3.3.2, R Foundation for Statistical Computing, Vienna, Austria) was used for statistical analysis. From 59 patients, 45 retinal drawings were available – 43 drawn digitally and two drawn on paper. Two patients were excluded for exceeding the 10 mm RRD border distance to the fovea. Figure 1 A depicts the correlation between the retinal drawings and the objective OCT distance taken immediately after examination. Retinal drawings deviated significantly from the ideal no difference between drawing and objectively measured RRD border distance from the fovea (p < 0.0001). A split-fovea patient would on average be drawn 3.31 mm from the fovea, whereas an RRD border 6.0 mm from the fovea would be drawn 4.32 mm from the fovea. Almost half of the patients (20/43, 46.5%) had routine OCT performed prior to examination (TOPCON OCT 3D 2000 – 6 × 6 mm macular scan) (Topcon Corporation, Tokyo, Japan) with the RRD border visible in 13 of these scans. The fovea threatening RRDs visualized on OCT were somewhat more accurately identified; a split fovea would on average be drawn 2.05 mm from the fovea if OCT was available. Although OCT seemed to aid in more accurate retinal drawings, it did not represent a significant improvement over no OCT visualization of the RRD (p = 0.175). Thus, with retinal drawings it is worth noting that RRDs close to the fovea are at risk of being labelled as far away and vice versa. We suspect that the bullous components of the RRD draw attention while flatter components are easier to miss. We suggest that the OCT be used more actively in RRD diagnosis to accurately communicate the RRD status to the patient and other healthcare personnel as well as aid ophthalmology residents in accurately interpreting ophthalmoscopic findings.

BackgroundEarly diagnosis of non-melanoma skin cancer (NMSC) is potentially possible using optical coherence tomography (OCT) which provides non-invasive, real-time images of skin with micrometre resolution and an imaging depth of up to 2mm. OCT technology for skin imaging has undergone significant developments, improving image quality substantially. The diagnostic accuracy of any method is influenced by continuous technological development making it necessary to regularly re-evaluate methods. ObjectiveThe objective of this study is to estimate the diagnostic accuracy of OCT in basal cell carcinomas (BCC) and actinic keratosis (AK) as well as differentiating these lesions from normal skin. MethodsA study set consisting of 142 OCT images meeting selection criterea for image quality and diagnosis of AK, BCC and normal skin was presented uniformly to two groups of blinded observers: 5 dermatologists experienced in OCT-image interpretation and 5 dermatologists with no experience in OCT. During the presentation of the study set the observers filled out a standardized questionnaire regarding the OCT diagnosis. Images were captured using a commercially available OCT machine (Vivosight ®, Michelson Diagnostics, UK). ResultsSkilled OCT observers were able to diagnose BCC lesions with a sensitivity of 86% to 95% and a specificity of 81% to 98%. Skilled observers with at least one year of OCT-experience showed an overall higher diagnostic accuracy compared to inexperienced observers. ConclusionsThe study shows an improved diagnostic accuracy of OCT in differentiating AK and BCC from healthy skin using state-of-the-art technology compared to earlier OCT technology, especially concerning BCC diagnosis.

Optical coherence tomography (OCT) is a new technique for micron scale, cross-sectional, tomographic imaging.1 In biology and medicine, OCT can be a powerful technique for optical biopsy because it permits the direct imaging of cross-sectional tissue architectural morphology without the need to excisionally remove specimens. OCT imaging is somewhat analogous to radar or ultrasound, except that OCT uses a low coherence optical source and interferometry to perform time delay measurement of light which is backreflected or backscattered from optically turbid specimens. Superluminescent diodes can provide 15-20 micron resolution imaging at several fixed wavelengths, including 800 and 1300 nm, but output powers are limited to the order of a milliwatt. Studies at these wavelengths have demonstrated that 1300 nm wavelengths can achieve greater imaging penetration depths in biological tissues because of reduced scattering. Ultrahigh resolution imaging has been demonstrated using the fluorescent emission from solid state laser media2 and femtosecond pulses from a mode locked Ti:Al2O3 laser.3 OCT using mode locked solid state lasers3 is especially promising because the high output powers available enable higher signal to noise levels as well as faster data acquisition. Using a mode locked source, OCT imaging rates approaching real time can be achieved. In addition, the spectral bandwidth of femtosecond pulses can be broadened by using self phase modulation in an optical fiber thus yielding significant increases in imaging resolution. In this paper we present a Kerr lens mode locked Forsterite laser (at 1.3 micron wavelength) which is spectrally broadened through self-phase modulation in a dispersion shifted fiber. With this source 5.7 micron resolution OCT images with 116 dB signal to noise are demonstrated. Applications of mode locked solid state technology for OCT biomedical imaging is discussed.

Extracting optical properties of tissue [e.g., the attenuation coefficient () and the backscattering fraction] from the optical coherence tomography (OCT) images is a valuable tool for parametric imaging and related diagnostic applications. Previous attenuation estimation models depend on the assumption of the uniformity of the backscattering fraction () within layers or whole samples, which does not accurately represent real-world conditions. Our aim is to develop a robust and accurate model that calculates depth-wise values of attenuation and backscattering fractions simultaneously from OCT signals. Furthermore, we aim to develop an attenuation compensation model for OCT images that utilizes the optical properties we obtained to improve the visual representation of tissues. Using the stationary iteration method under suitable constraint conditions, we derived the approximated solutions of and on a single scattering model. During the iteration, the estimated value of can be rectified by introducing the large variations of , whereas the small ones were automatically ignored. Based on the calculation of the structure information, the OCT intensity with attenuation compensation was deduced and compared with the original OCT profiles. The preliminary validation was performed in the OCT A-line simulation and Monte Carlo modeling, and the subsequent experiment was conducted on multi-layer silicone-dye- phantoms and ex vivo cow eyes. Our method achieved robust and precise estimation of and for both simulated and experimental data. Moreover, corresponding OCT images with attenuation compensation provided an improved resolution over the entire imaging range. Our proposed method was able to correct the estimation bias induced by the variations of and provided accurate depth-resolved measurements of both and simultaneously. The method does not require prior knowledge of the morphological information of tissue and represents more real-life tissues. Thus, it has the potential to help OCT imaging based disease diagnosis of complex and multi-layer biological tissue.

To evaluate how information from combined coronal optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (SLO) with integrated simultaneous indocyanine green (ICG) dye angiography can be used in the diagnosis of a variety of macular diseases. A compact chin-rest-based OCT/confocal imaging system was used to produce the OCT image and excite the fluorescence in the ICG dye. The same eye fundus area can be visualized with coronal (C-scans, en face) OCT and ICG angiography simultaneously. Fast T scanning (transverse scanning, en face) was used to build B- or C-scan OCT images along with confocal SLO views, with and without ICG filtration. The OCT, confocal SLO and ICG fluorescence images were simultaneously presented in a three-screen format. A live mixing channel overlaid the ICG sequence on the coronal OCT slices in a fourth panel for immediate comparison. Thirty eyes were imaged. The pathologic conditions studied included classic and occult neovascular membranes, vascularized RPE detachments, polypoidal choroidal vasculopathy, traumatic choroidal rupture, diabetic maculopathy, central serous retinopathy, and macular drusen. Images were evaluated with special attention toward identifying novel relationships between morphology and function revealed by the superimposition of the studies. Simultaneous visualization of an en face (coronal, C-scan) OCT image and of an ICG angiogram, displayed side by side and superimposed, permits more precise correlations between late fluorescence accumulation with structures deep to the retinal surface at the retina-choroid interface. The multiplanar scanning also permits immediate B-scan OCT cross-sectional views of regions of abnormal fluorescence. The paper demonstrates the synergy between the two types of studies, functional and anatomic, in providing a more complete view of the pathologic condition.