Ultrahigh-resolution Optical Coherence Tomography Imaging Research Articles

Classifying breast cancer in ultrahigh-resolution optical coherence tomography images using convolutional neural networks.

Optical coherence tomography (OCT) is being investigated in breast cancer diagnostics as a real-time histology evaluation tool. We present a customized deep convolutional neural network (CNN) for classification of breast tissues in OCT B-scans. Images of human breast samples from mastectomies and breast reductions were acquired using a custom ultrahigh-resolution OCT system with 2.72 µm axial resolution and 5.52 µm lateral resolution. The network achieved 96.7% accuracy, 92% sensitivity, and 99.7% specificity on a dataset of 23 patients. The usage of deep learning will be important for the practical integration of OCT into clinical practice.

Comparative Study of Conventional and Ultrahigh-resolution Optical Coherence Tomography Imaging in Esophageal Neoplasia

Early diagnosis of esophageal cancer can be enhanced by the application of optical coherence tomography (OCT) to gastrointestinal endoscopy. One of the most salient examples is the use of OCT to augment the detection of dysplasia during Barrett's esophagus (BE) surveillance, the established precursor to esophageal adenocarcinoma (EAC). 1 Reid BJ Li X Galipeau PC et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010; 10: 87-101https://doi.org/10.1038/nrc2773 Crossref PubMed Scopus (303) Google Scholar , 2 Pohl H Welch HG The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005; 97: 142-146https://doi.org/10.1093/jnci/dji024 Crossref PubMed Scopus (1069) Google Scholar A previously commercially available balloon-based imaging catheter system, also known as volumetric laser endomicroscopy (VLE), was designed to provide circumferential esophageal imaging at the time of endoscopy. The VLE system uses a 1300 nm wavelength-swept laser and provides images with an axial resolution of 7 µm up to a depth of 3 mm. VLE is capable of resolving microarchitectural features associated with early neoplasia in BE including irregular glandular morphology and increased surface signal intensity. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Scoring systems that incorporate these features are associated with a sensitivity of 76-83% and specificity of 71-79% in the diagnosis of BE neoplasia. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar , 4 Swager AF Tearney GJ Leggett CL et al. Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett’s esophagus using high-quality histological correlation. Gastrointest Endosc. 2017; 85: 918-926.e7https://doi.org/10.1016/j.gie.2016.09.012 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Similarly, esophageal OCT has been used in the diagnosis and staging of squamous cell carcinoma (ESCC) where layer effacement predicts the depth of invasion. 5 Trindade AJ Benias PC Inamdar S et al. Use of volumetric laser endomicroscopy for determining candidates for endoscopic therapy in superficial esophageal squamous cell carcinoma. United European Gastroenterol J. 2018; 6: 838-845https://doi.org/10.1177/2050640618761701 Crossref PubMed Scopus (5) Google Scholar In the last decade, ultra-high resolution (UHR) OCT systems that operate at 800 nm and achieve an axial resolution closer to 2.5 µm have been developed. Our group previously described a super-achromatic OCT capsule designed for UHR esophageal imaging. 6 Li K Liang W Mavadia-Shukla J et al. Super-achromatic optical coherence tomography capsule for ultrahigh-resolution imaging of esophagus. J Biophotonics. 2019; 12e201800205https://doi.org/10.1002/jbio.201800205 Crossref PubMed Scopus (16) Google Scholar In the present study, we compare the imaging capability of UHR OCT to VLE in distinguishing microarchitectural features associated with esophageal neoplasia by imaging ex vivo esophageal resection specimens obtained from patients undergoing clinical endoscopy.

Evaluation of ultrahigh-resolution optical coherence tomography for basal cell carcinoma, seborrheic keratosis, and nevus.

Basal cell carcinoma, seborrheic keratosis, and nevus are common skin conditions. Though most of the skin diseases can be distinguished from each other by physician's naked eyes, the diagnostic accuracy is not 100%. The accurate diagnosis and assessment of three diseases make a big difference on the clinical management. Nowadays, biopsy is still the gold standard for diagnosis even it is invasive, time-consuming, and painful. Ultrahigh-resolution optical coherence tomography is an emerging technology that can produce in situ, cellular-resolution, real-time, continuous, 3D images in a noninvasive way. In our study, four basal cell carcinoma patients, five seborrheic keratosis patients, and 10 nevus patients who were diagnosed by histology were studied by ultrahigh-resolution optical coherence tomography after visual examination by experienced dermatologists. Cellular contrast was utilized to clearly identify the features of the three skin diseases. The features including such as hyperkeratosis (horn pseudocysts), papillomatosis, intraepidermal nests, elongated, and expanded rete ridge can be visualized in seborrheic keratosis. Tumor nodular, mucin surrounding with tumor (retraction space in histopathology), tumor subtype, and necrosis were featured in basal cell carcinoma. Pigment was characterized in epidermis and dermis. The comparison of ultrahigh-resolution optical coherence tomography images reveals a strong correlation with histological images. Ultrahigh-resolution optical coherence tomography can complement existing diagnostic techniques for investigating seborrheic keratosis, basal cell carcinoma and nevus, and show enormous potential in vivo applications for the three skin diseases in the future.

Machine learning helps improve diagnostic ability of subclinical keratoconus using Scheimpflug and OCT imaging modalities

PurposeTo develop an automated classification system using a machine learning classifier to distinguish clinically unaffected eyes in patients with keratoconus from a normal control population based on a combination of Scheimpflug camera images and ultra-high-resolution optical coherence tomography (UHR-OCT) imaging data.MethodsA total of 121 eyes from 121 participants were classified by 2 cornea experts into 3 groups: normal (50 eyes), with keratoconus (38 eyes) or with subclinical keratoconus (33 eyes). All eyes were imaged with a Scheimpflug camera and UHR-OCT. Corneal morphological features were extracted from the imaging data. A neural network was used to train a model based on these features to distinguish the eyes with subclinical keratoconus from normal eyes. Fisher’s score was used to rank the differentiable power of each feature. The receiver operating characteristic (ROC) curves were calculated to obtain the area under the ROC curves (AUCs).ResultsThe developed classification model used to combine all features from the Scheimpflug camera and UHR-OCT dramatically improved the differentiable power to discriminate between normal eyes and eyes with subclinical keratoconus (AUC = 0.93). The variation in the thickness profile within each individual in the corneal epithelium extracted from UHR-OCT imaging ranked the highest in differentiating eyes with subclinical keratoconus from normal eyes.ConclusionThe automated classification system using machine learning based on the combination of Scheimpflug camera data and UHR-OCT imaging data showed excellent performance in discriminating eyes with subclinical keratoconus from normal eyes. The epithelial features extracted from the OCT images were the most valuable in the discrimination process. This classification system has the potential to improve the differentiable power of subclinical keratoconus and the efficiency of keratoconus screening.

Multi-modal Anterior Eye Imager Combining Ultra-High Resolution OCT and Microvascular Imaging for Structural and Functional Evaluation of the Human Eye

To establish complementary information for the diagnosis and evaluation of ocular surface diseases, we developed a multi-modal, non-invasive optical imaging platform by combining ultra-high resolution optical coherence tomography (UHR-OCT) with a microvascular imaging system based on slit-lamp biomicroscopy. Our customized UHR-OCT module achieves an axial resolution of ≈2.9 μm in corneal tissue with a broadband light source and an A-line acquisition rate of 24 kHz with a line array CCD camera. The microvascular imaging module has a lateral resolution of 3.5 μm under maximum magnification of ≈187.5× with an imaging rate of 60 frames/s, which is sufficient to image the conjunctival vessel network and record the movement trajectory of clusters of red blood cells. By combining the imaging optical paths of different modules, our customized multi-modal anterior eye imaging platform is capable of performing real-time cross-sectional UHR-OCT imaging of the anterior eye, conjunctival vessel network imaging, high-resolution conjunctival blood flow videography, fluorescein staining and traditional slit-lamp imaging on a single device. With self-developed software, a conjunctival vessel network image and blood flow videography were further analyzed to acquire quantitative morphological and hemodynamics parameters, including vessel fractal dimensions, blood flow velocity and vessel diameters. The ability of our multi-modal anterior eye imager to provide both structural and functional information for ophthalmic clinical applications was demonstrated on a healthy human subject and a keratitis patient.

Corneal epithelial thickness profile in dry-eye disease.

To characterize and evaluate the use of corneal epithelial profile maps generated by an ultrahigh-resolution optical coherence tomography (UHR-OCT) in the diagnosis and management of dry-eye disease (DED). This prospective, interventional case-control study included 115 eyes of 71 subjects (52 DED and 19 controls) imaged using an UHR-OCT. Average, maximum, and minimum, range of corneal epithelial thicknesses were extracted from epithelial profile maps. Surface regularity was quantified using the range and variance of the epithelial thickness measured along a horizontal UHR-OCT scan. The variance of thickness measurements along a scan was named epithelial irregularity factor (EIF). Symptoms of 31 DED patients (55 eyes) were quantified by questionnaire and correlated to epithelial profile findings, fluorescein staining, tear breakup time, and Schirmer's test. Twenty-one DED eyes were administered autologous serum drops and follow-up UHR-OCT images were captured. DED patients had a highly irregular corneal epithelial surface compared with controls. Epithelial thickness profile variance (EIF) and range were significantly higher in DED as compared with controls (5.79 vs. 0.77, p < 0.001 and 7.6 vs. 4.6 μm, p < 0.001). Both parameters were highly significantly correlated with questionnaire scores (EIF: r = 0.778; p < 0.001, range: r = 0.737; p < 0.001). Follow-up showed a statistically significant reduction in epithelial thickness profile variance and range of treated patients ( p < 0.001). DED patients have irregular epithelial surface that can be quantified using UHR-OCT generated CEP maps. Epithelial thickness profile range and EIF correlate accurately with patients' symptoms and could be used to follow-up patients and response to treatment.

Automatic evaluation of stratum basale and dermal papillae using ultrahigh resolution optical coherence tomography

Diagnosis of many skin conditions requires evaluation of dermal papillae and stratum basale, such as vitiligo. In clinical practice, imaging dermal papillae structures relies on excisional biopsy followed by histological processing and analysis. As biopsy is invasive and associated with complications, a noninvasive imaging method such as optical coherence tomography (OCT) can complement the existing method by enabling large area scanning. However, because OCT image analysis requires training and it takes time to review OCT images from large skin areas, an automatic evaluation method is preferred to reduce the workload and avoid ‘sampling errors’ during image analysis. Here we report an automatic method to enhance and detect dermal papillae and stratum basale in ultrahigh resolution OCT images. A high detection accuracy is achieved by rejecting image artifacts using a surface flattening algorithm and an artifact recognition algorithm. We further demonstrated the efficacy of this automatic method in detecting vitiligo in human subjects.

Morphological and functional changes in the rat retina associated with 2 months of intermittent moderate intraocular pressure elevation

Morphological and functional changes in the rat retina and optic nerve head (ONH), associated with 8 weeks of intermittent moderately elevated intraocular pressure (IOP) were measured with a combined ultrahigh resolution optical coherence tomography (UHR-OCT) and electroretinography (ERG) system. The IOP of male Sprague-Dawley rats was raised in one eye to ~35 mmHg for 1 hour/day on 6 days each week using vascular loops. Single-flash ERG traces and volumetric UHR-OCT images of the ONH were acquired from both eyes before, during and after IOP elevations at weeks 1, 5 and 9 of the study. The UHR-OCT images showed depression of the posterior eye around the ONH during the IOP elevations, the magnitude of which increased significantly from week 1 to week 9 (p = 0.01). The ERG a-wave and b-wave amplitudes increased temporarily during IOP elevations and returned to normal ~30 minutes after loop removal. Recurrent intermittent IOP spikes caused > 30% decrease in the ERG a-wave and b-wave amplitudes measured during the IOP elevations over the course of 2 months. This study suggests that recurrent, relatively short-duration IOP spikes for extended period of time are associated with peri-ONH tissue hypercompliance and reduced retinal functional response to visual stimulation during acute IOP elevation.

Broadband rotary joint for high-speed ultrahigh-resolution endoscopic OCT imaging at 800 nm

We report the development of a broadband rotary joint for high-speed ultrahigh-resolution endoscopic optical coherence tomography (OCT) imaging in the 800nm spectral range. This rotary joint features a pair of achromatic doublets in order to achieve broadband operation for a 3dB bandwidth over 150nm. The measured one-way throughput of the rotary joint is greater than 80%, while the fluctuation of the double-pass coupling efficiency during 360deg rotation is less than ±5% at a near video-rate speed of 20 revolutions/s (rps). The rotary joint is used in conjunction with a diffractive-optics-based endoscope and 800nm spectral domain OCT system and achieved an ultrahigh axial resolution of ∼2.4 μm in air. The imaging performance is demonstrated by 3D circumferential imaging of a mouse colon in vivo.

Pigmented and albino rats differ in their responses to moderate, acute and reversible intraocular pressure elevation.

To compare the electrophysiological and morphological responses to acute, moderately elevated intraocular pressure (IOP) in Sprague-Dawley (SD), Long-Evans (LE) and Brown Norway (BN) rat eyes. Eleven-week-old SD (n=5), LE (n=5) and BN (n=5) rats were used. Scotopic threshold responses (STRs), Maxwellian flash electroretinograms (ERGs) or ultrahigh-resolution optical coherence tomography (UHR-OCT) images of the rat retinas were collected from both eyes before, during and after IOP elevation of one eye. IOP was raised to ~35mmHg for 1h using a vascular loop, while the other eye served as a control. STRs, ERGs and UHR-OCT images were acquired on 3days separated by 1day of no experimental manipulation. There were no significant differences between species in baseline electroretinography. However, during IOP elevation, peak positive STR amplitudes in LE (mean±standard deviation 259±124µV) and BN (228±96µV) rats were about fourfold higher than those in SD rats (56±46µV) rats (p=0.0002 for both). Similarly, during elevated IOP, ERG b-wave amplitudes were twofold higher in LE and BN rats compared to those of SD rats (947±129µV and 892±184µV, vs 427±138µV; p=0.0002 for both). UHR-OCT images showed backward bowing in all groups during IOP elevation, with a return to typical form about 30min after IOP elevation. Differences in the loop-induced responses between the strains are likely due to different inherent retinal morphology and physiology.

Ultrahigh-resolution OCT imaging of the human cornea

We present imaging of corneal pathologies using optical coherence tomography (OCT) with high resolution. To this end, an ultrahigh-resolution spectral domain OCT (UHR-OCT) system based on a broad bandwidth Ti:sapphire laser is employed. With a central wavelength of 800 nm, the imaging device allows to acquire OCT data at the central, paracentral and peripheral cornea as well as the limbal region with 1.2 µm x 20 µm (axial x lateral) resolution at a rate of 140 000 A-scans/s. Structures of the anterior segment of the eye, not accessible with commercial OCT systems, are visualized. These include corneal nerves, limbal palisades of Vogt as well as several corneal pathologies. Cases such as keratoconus and Fuchs's endothelial dystrophy as well as infectious changes caused by diseases like Acanthamoeba keratitis and scarring after herpetic keratitis are presented. We also demonstrate the applicability of our system to visualize epithelial erosion and intracorneal foreign body after corneal trauma as well as chemical burns. Finally, results after Descemet's membrane endothelial keratoplasty (DMEK) are imaged. These clinical cases show the potential of UHR-OCT to help in clinical decision-making and follow-up. Our results and experience indicate that UHR-OCT of the cornea is a promising technique for the use in clinical practice, but can also help to gain novel insight in the physiology and pathophysiology of the human cornea.

Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra-High Resolution OCT Imaging.

PurposeWe examined if light induces changes in the retinal structure that can be observed using optical coherence tomography (OCT).MethodsNormal C57BL/6J mice (age 3–6 months) adapted to either room light (15 minutes to ∼5 hours, 50–500 lux) or darkness (overnight) were imaged using a Bioptigen UHR-OCT system. Confocal histologic images were obtained from mice killed under light- or dark-adapted conditions.ResultsThe OCT image of eyes adapted to room light exhibited significant increases (6.1 ± 0.8 μm, n = 13) in total retina thickness compared to the same eyes after overnight dark adaptation. These light-adapted retinal thickness changes occurred mainly in the outer retina, with the development of a hyporeflective band between the RPE and photoreceptor-tip layers. Histologic analysis revealed a light-evoked elongation between the outer limiting membrane and Bruch's membrane from 45.8 ± 1.7 μm in the dark (n = 5) to 52.1 ± 3.7 μm (n = 5) in the light. Light-adapted retinas showed an increase of actin staining in RPE apical microvilli at the same location as the hyporeflective band observed in OCT images. Elongation of the outer retina could be detected even with brief light exposures, increasing 2.1 ± 0.3 μm after 15 minutes (n = 9), and 4.1 ± 1.0 μm after 2 hours (n = 6). Conversely, dark-adaptation caused outer retinal shortening of 1.4 ± 0.4 μm (n = 7) and 3.0 ± 0.5 μm (n = 8) after 15 minutes and 2 hours, respectively.ConclusionsLight-adaption induces an increase in the thickness of the outer retina and the appearance of a hyporeflective band in the OCT image. This is consistent with previous reports of light-induced fluid accumulation in the subretinal space.

High-power supercontinuum generation using high-repetition-rate ultrashort-pulse fiber laser for ultrahigh-resolution optical coherence tomography in 1600 nm spectral band

We describe the generation of a high-power, spectrally smooth supercontinuum (SC) in the 1600 nm spectral band for ultrahigh-resolution optical coherence tomography (UHR-OCT). A clean SC was achieved by using a highly nonlinear fiber with normal dispersion properties and a high-quality pedestal-free pulse obtained from a passively mode-locked erbium-doped fiber laser operating at 182 MHz. The center wavelength and spectral width were 1578 and 172 nm, respectively. The output power of the SC was 51 mW. Using the developed SC source, we demonstrated UHR-OCT imaging of biological samples with a sensitivity of 109 dB and an axial resolution of 4.9 µm in tissue.

Neurostimulation of the lacrimal nerve for enhanced tear production.

To design a proof-of-concept study to assess the effect of lacrimal nerve stimulation (LNS) with an implantable pulse generator (IPG) to increase aqueous tear production. Experimental animal study design of 6 Dutch Belted rabbits. Ultra high-resolution optical coherence tomography (UHR-OCT) quantified tear production by measuring the baseline tear volume of each rabbit's OD and OS. A neurostimulator was implanted adjacent to the right lacrimal nerve. After 2 minutes of LNS (100 μs, 1.6 mA, 20 Hz, 5-8 V), the tear volumes were measured with UHR-OCT. The change in tear volume was quantified and compared with the nonstimulated OS. Three rabbits underwent chronic LNS (100 μs, 1.6 mA, 10 Hz, 2 V) and their lacrimal glands were harvested for histopathologic analysis. The UHR-OCT imaging of the OD tear volume showed a 441% average increase in tear production after LNS as a percent of baseline. After stimulation, OD had statistically significant greater increase in tear volumes than OS (p = 0.028, Wilcoxon test). Poststimulation OD tear volumes were significantly greater compared with baseline (p = 0.028, Wilcoxon test). Histopathologic examination of the lacrimal glands showed no discernible tissue damage from chronic neurostimulation. In addition, there were no gross adverse effects on the general well-being of the animals due to chronic stimulation. LNS with an IPG appears to increase aqueous tear production. Chronic LNS showed no histopathologic lacrimal gland damage. This study suggests that LNS is a promising new treatment strategy to increase aqueous tear production.

Monitor corneal epithelial healing under bandage contact lens using ultrahigh-resolution optical coherence tomography after pterygium surgery.

To monitor corneal epithelial healing under bandage contact lens (BCL) using ultrahigh-resolution optical coherence tomography (UHR-OCT) after pterygium surgery. Thirty-nine eyes of 39 patients undergoing pterygium excision and conjunctival autografting were randomly allocated into 2 groups: 20 eyes were covered with silicone hydrogel BCLs at the end of surgery and 19 eyes served as a control. Ultrahigh-resolution optical coherence tomography scans of the cornea were performed sequentially at 1, 2, and 3 days, and then every other day until the end of re-epithelialization after surgery. Complete epithelial healing was verified with fluorescein staining examination after removal of BCLs. Postsurgery pain was evaluated using the visual analog scale. All BCLs were successfully fit without any contact lens-related complications. Ultrahigh-resolution optical coherence images clearly revealed the architectural features of postoperative cornea with BCL in situ and showed epithelial healing process. Ultrahigh-resolution optical coherence tomography imaging agreed with the fluorescein staining examinations in detecting corneal epithelial defect. Based on the assessment by UHR-OCT, the average time course of re-epithelialization in the BCL group was 3.9±1.2 days, whereas in the control group, it was 5.7±1.8 days (P=0.001). Visual analog scale scoring showed lower pain levels in the BCL group comparing with the control group at each point of time (all P<0.05). Ultrahigh-resolution optical coherence tomography is an excellent tool in monitoring corneal epithelial healing under BCLs and determining the appropriate time for lens removal. Silicone hydrogel BCL is recommended as an adjuvant therapy after pterygium surgery for its efficacy in improving re-epithelialization and postoperative comfort.

Non-invasive detection of early retinal neuronal degeneration by ultrahigh resolution optical coherence tomography.

Optical coherence tomography (OCT) has revolutionises the diagnosis of retinal disease based on the detection of microscopic rather than subcellular changes in retinal anatomy. However, currently the technique is limited to the detection of microscopic rather than subcellular changes in retinal anatomy. However, coherence based imaging is extremely sensitive to both changes in optical contrast and cellular events at the micrometer scale, and can generate subtle changes in the spectral content of the OCT image. Here we test the hypothesis that OCT image speckle (image texture) contains information regarding otherwise unresolvable features such as organelle changes arising in the early stages of neuronal degeneration. Using ultrahigh resolution (UHR) OCT imaging at 800 nm (spectral width 140 nm) we developed a robust method of OCT image analyses, based on spatial wavelet and texture-based parameterisation of the image speckle pattern. For the first time we show that this approach allows the non-invasive detection and quantification of early apoptotic changes in neurons within 30 min of neuronal trauma sufficient to result in apoptosis. We show a positive correlation between immunofluorescent labelling of mitochondria (a potential source of changes in cellular optical contrast) with changes in the texture of the OCT images of cultured neurons. Moreover, similar changes in optical contrast were also seen in the retinal ganglion cell- inner plexiform layer in retinal explants following optic nerve transection. The optical clarity of the explants was maintained throughout in the absence of histologically detectable change. Our data suggest that UHR OCT can be used for the non-invasive quantitative assessment of neuronal health, with a particular application to the assessment of early retinal disease.

Diffractive catheter for ultrahigh-resolution spectral-domain volumetric OCT imaging

We present a novel design for an endoscopic imaging catheter utilizing diffractive optics for ultrahigh-resolution optical coherence tomography (OCT) imaging at 800 nm. A diffractive microlens was developed to alleviate severe chromatic aberration when a broadband light source was employed at the 800 nm wavelength range. Combined with a home-built fiber rotary joint and a broadband Ti:sapphire laser, the imaging catheter achieved a lateral resolution of 6.2 μm and an axial resolution of 3.0 μm in air. The performance of the catheter was demonstrated by three-dimensional full-circumferential endoscopic OCT imaging of guinea pig esophagus in vivo.

Development of a high power supercontinuum source in the 17 μm wavelength region for highly penetrative ultrahigh-resolution optical coherence tomography

We developed a high power supercontinuum source at a center wavelength of 1.7 μm to demonstrate highly penetrative ultrahigh-resolution optical coherence tomography (UHR-OCT). A single-wall carbon nanotube dispersed in polyimide film was used as a transparent saturable absorber in the cavity configuration and a high-repetition-rate ultrashort-pulse fiber laser was realized. The developed SC source had an output power of 60 mW, a bandwidth of 242 nm full-width at half maximum, and a repetition rate of 110 MHz. The average power and repetition rate were approximately twice as large as those of our previous SC source [20]. Using the developed SC source, UHR-OCT imaging was demonstrated. A sensitivity of 105 dB and an axial resolution of 3.2 μm in biological tissue were achieved. We compared the UHR-OCT images of some biological tissue samples measured with the developed SC source, the previous one, and one operating in the 1.3 μm wavelength region. We confirmed that the developed SC source had improved sensitivity and penetration depth for low-water-absorption samples.

Stochastic speckle noise compensation in optical coherence tomography using non-stationary spline-based speckle noise modelling.

Optical coherence tomography (OCT) allows for non-invasive 3D visualization of biological tissue at cellular level resolution. Often hindered by speckle noise, the visualization of important biological tissue details in OCT that can aid disease diagnosis can be improved by speckle noise compensation. A challenge with handling speckle noise is its inherent non-stationary nature, where the underlying noise characteristics vary with the spatial location. In this study, an innovative speckle noise compensation method is presented for handling the non-stationary traits of speckle noise in OCT imagery. The proposed approach centers on a non-stationary spline-based speckle noise modeling strategy to characterize the speckle noise. The novel method was applied to ultra high-resolution OCT (UHROCT) images of the human retina and corneo-scleral limbus acquired in-vivo that vary in tissue structure and optical properties. Test results showed improved performance of the proposed novel algorithm compared to a number of previously published speckle noise compensation approaches in terms of higher signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and better overall visual assessment.

Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography

The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.