Simultaneous Optical Coherence Tomography Research Articles

Handheld contact-type OCT and color fundus system for retinal imaging.

We present proof of concept for a handheld contact-type system capable of simultaneous optical coherence tomography (OCT) imaging of the retina and wide-field digital fundus color photography. The study focuses on demonstrating the feasibility of the proposed approach, particularly for eventual use in pediatric patients during examination under anesthesia in the operating room and in the neonatal intensive care unit. Direct contact of the probe with the cornea allows the photographer to maintain a stable position during imaging, reducing motion artifacts in the OCT images. Additionally, it simplifies the alignment process and increases the field of view of the optics. By integrating OCT and fundus imaging into a single device, the proposed compact modular design eliminates the need for separate, space-consuming systems dedicated to each imaging modality.

Motion Contrast, Phase Gradient, and Simultaneous OCT Images Assist in the Interpretation of Dark-Field Images in Eyes with Retinal Pathology.

The cellular-level visualization of retinal microstructures such as blood vessel wall components, not available with other imaging modalities, is provided with unprecedented details by dark-field imaging configurations; however, the interpretation of such images alone is sometimes difficult since multiple structural disturbances may be present in the same time. Particularly in eyes with retinal pathology, microstructures may appear in high-resolution retinal images with a wide range of sizes, sharpnesses, and brightnesses. In this paper we show that motion contrast and phase gradient imaging modalities, as well as the simultaneous acquisition of depth-resolved optical coherence tomography (OCT) images, provide additional insight to help understand the retinal neural and vascular structures seen in dark-field images and may enable improved diagnostic and treatment plans.

The compatibility between optical coherence tomography and fundus fluorescein angiography in the detection of macular edema involving the fovea

Objective: To investigate the compatibility between optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) in the detection of macular edema (ME) excluding subretinal fluid (SRF) involving the fovea. Materials and methods: In this retrospective study in the Ophthalmology Department at our university hospital, interpretation of OCT and FFA images was performed for 200 eyes that underwent simultaneous FFA and OCT to rule out ME. The cases having SRF were excluded from the study. Results: Of 200 eyes, 193 eyes (96.5%) had the finding of ME confirmed by both techniques. There were 2 eyes (1%) for which FFA revealed ME involving fovea with hyperfluorescence in the macula while OCT demonstrated no intraretinal edema or subretinal fluid in the macula. For 5 eyes in the study (2.5%), OCT revealed intraretinal edema in the fovea, while these were not detected by FFA. Conclusion: This study suggests that FFA and OCT are highly sensitive techniques for the detection of ME and they correlate with each other. The little discrepancy between OCT and FFA for determining ME may be due to intracellular or extracellular edema and fast or slower development of retinal edema.

Multimodal imaging needle combining optical coherence tomography and fluorescence for imaging of live breast cancer cells labeled with a fluorescent analog of tamoxifen.

.SignificanceImaging needles consist of highly miniaturized focusing optics encased within a hypodermic needle. The needles may be inserted tens of millimeters into tissue and have the potential to visualize diseased cells well beyond the penetration depth of optical techniques applied externally. Multimodal imaging needles acquire multiple types of optical signals to differentiate cell types. However, their use has not previously been demonstrated with live cells.AimWe demonstrate the ability of a multimodal imaging needle to differentiate cell types through simultaneous optical coherence tomography (OCT) and fluorescence imaging.ApproachWe characterize the performance of a multimodal imaging needle. This is paired with a fluorescent analog of the therapeutic drug, tamoxifen, which enables cell-specific fluorescent labeling of estrogen receptor-positive (ER+) breast cancer cells. We perform simultaneous OCT and fluorescence in situ imaging on MCF-7 ER+ breast cancer cells and MDA-MB-231 ER− cells. Images are compared against unlabeled control samples and correlated with standard confocal microscopy images.ResultsWe establish the feasibility of imaging live cells with these miniaturized imaging probes by showing clear differentiation between cancerous cells.ConclusionsImaging needles have the potential to aid in the detection of specific cancer cells within solid tissue.

Association of Cerebrospinal Fluid Parameters and Neurofilament Light Chain With Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis.

IntroductionMultiple sclerosis (MS) pathophysiology comprises both inflammatory and neurodegenerative characteristics. Cerebrospinal fluid (CSF) analysis allows for assessment of inflammation while neurofilament light chain can indicate neuroaxonal damage. Retinal thinning is a robust prognostic biomarker for neurodegeneration in MS. To date, an association between CSF parameters upon MS diagnosis and retinal thinning has not been investigated.Aims and ObjectivesWe aimed to determine whether CSF parameters are associated with the evolution of retinal layer thinning in people with MS (pwMS).MethodsFor this longitudinal observational study, we investigated pwMS from the Vienna MS database (VMSD), who had undergone (1) a diagnostic lumbar puncture (LP) between 2015 and 2020, and (2) simultaneous optical coherence tomography (OCT) and/or (3) a follow-up OCT scan. Linear stepwise regression models were calculated with OCT parameters (peripapillary retinal nerve fiber layer [pRNFL] thickness at LP and at follow-up, annualized loss of pRNFL thickness [aLpRNFL]) as a dependent variable, and CSF parameters (white blood cell [WBC] count, total protein [CSFTP], CSF/serum albumin ratio [Qalb], intrathecal synthesis of immunoglobulins, neurofilament light chain [NfL] in both CSF and serum [CSFNfL/sNfL]) as independent variables adjusted for age, sex, and disease duration.ResultsWe analyzed 61 pwMS (median age 30.0 years [interquartile range 25.5–35.0], 57.4% female, median disease duration 1.0 month [IQR 0–2.0] before LP, median follow-up 1.9 years [IQR 1.1–3.5]). CSFNfL and sNfL measurements were available in 26 and 31 pwMS, respectively. pRNFL thickness at LP was inversely associated with the CSF WBC count (β = −0.36; 95% CI −0.51, −0.08; p = 0.008). We did not find any association between other CSF parameters, including CSFNfL, sNfL, and aLpRNFL.ConclusionsIncreased WBC count as an indicator of acute inflammation and blood-brain-barrier breakdown seems to be associated with the amount of retinal thickness already lost at the time of LP. However, neither routine CSF parameters nor a singular NfL measurement allows the prediction of future retinal thinning.

3D-Printed Micro Lens-in-Lens for In Vivo Multimodal Microendoscopy.

Multimodal microendoscopes enable co-located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high-sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high-quality multiple modalities simultaneously. An optical design is demonstrated which uses two-photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens-in-lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber-optic design approaches. This lens-in-lens is then integrated into an intravascular catheter probe with a diameter of 520µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.

Simultaneous visible light optical coherence tomography and near infrared OCT angiography in retinal pathologies: A case study.

A dual-channel optical coherence tomography system with wavelengths in the visible and near-infrared light ranges can provide both structural and functional information for retinal microvasculature simultaneously. We applied this integrated system in an ongoing clinical study of patients with various retinal pathologies. Here, we present case study results of patients with diabetic retinopathy, central retinal vein occlusion, and sickle cell retinopathy compared to a healthy subject. For the first time, this comparison validates the system's ability to detect structural anomalies in both en face and B-scan images with simultaneous retinal optical coherence tomography angiography and measurement of sO2 in parafoveal vessels that are around 20-30 µm in diameter. This integrated system represents a powerful instrument with potentially far-reaching clinical implications for the early detection and diagnosis of retinal vascular diseases.

A novel optical needle probe for deep learning-based tissue elasticity characterization

Abstract The distinction between malignant and benign tumors is essential to the treatment of cancer. The tissue's elasticity can be used as an indicator for the required tissue characterization. Optical coherence elastography (OCE) probes have been proposed for needle insertions but have so far lacked the necessary load sensing capabilities. We present a novel OCE needle probe that provides simultaneous optical coherence tomography (OCT) imaging and load sensing at the needle tip. We demonstrate the application of the needle probe in indentation experiments on gelatin phantoms with varying gelatin concentrations. We further implement two deep learning methods for the end-toend sample characterization from the acquired OCT data. We report the estimation of gelatin sample weight ratios [wt%] in unseen samples with a mean error of 1.21 ± 0.91 wt%. Both evaluated deep learning models successfully provide sample characterization with different advantages regarding the accuracy and inference time.

A Silk‐Based Functionalization Architecture for Single Fiber Imaging and Sensing

AbstractA new fiber functionalization architecture for single‐fiber imaging and sensing is presented. 5(6)Carboxy‐seminaphthorhodafluor‐2 (a fluorescent pH sensor) is attached to a silk‐binding peptide and the complex added to aqueous silk fibroin protein. These bind with a Kd of 36 µM as determined by a fluorescence polarization assay. The fiber is dip‐coated into the silk and peptide mixture, and scanning electron microscopy images reveal a uniform silk coating on the fiber tip. The coating is stable to repeated washes and does not affect the imaging light emitted from the fiber, which allows concurrent optical coherence tomography (OCT) imaging and pH sensing. Oocytes are metabolically stimulated with CoCl2 to produce lactic acid, and a pH reduction of 0.04 is measured using the probe. The distance between fiber tip and oocyte is monitored by simultaneous OCT acquisitions to precisely position the probe. Lastly, OCT imaging of an ovary revealed the presence/absence of an oocyte within a follicle, an important step toward improving patient outcomes during in vitro fertilization, by limiting the number of invasive follicle punctures required. These results demonstrate the utility of this new coating to enable simultaneous OCT imaging and sensing, which provides significant insight into complex biological systems.

Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery.

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery.

Multimodal endoscopy for colorectal cancer detection by optical coherence tomography and near-infrared fluorescence imaging.

While colonoscopy is the gold standard for diagnosis and classification of colorectal cancer (CRC), its sensitivity and specificity are operator-dependent and are especially poor for small and flat lesions. Contemporary imaging modalities, such as optical coherence tomography (OCT) and near-infrared (NIR) fluorescence, have been investigated to visualize microvasculature and morphological changes for detecting early stage CRC in the gastrointestinal (GI) tract. In our study, we developed a multimodal endoscopic system with simultaneous co-registered OCT and NIR fluorescence imaging. By introducing a contrast agent into the vascular network, NIR fluorescence is able to highlight the cancer-suspected area based on significant change of tumor vascular density and morphology caused by angiogenesis. With the addition of co-registered OCT images to reveal subsurface tissue layer architecture, the suspected regions can be further investigated by the altered light scattering resulting from the morphological abnormality. Using this multimodal imaging system, an in vivo animal study was performed using a F344-ApcPircUwm rat, in which the layered architecture and microvasculature of the colorectal wall at different time points were demonstrated. The co-registered OCT and NIR fluorescence images allowed the identification and differentiation of normal colon, hyperplastic polyp, adenomatous polyp, and adenocarcinoma. This multimodal imaging strategy using a single imaging probe has demonstrated the enhanced capability of identification and classification of CRC compared to using any of these technologies alone, thus has the potential to provide a new clinical tool to advance gastroenterology practice.

Simultaneous multi-spatial scanning optical coherence tomography (OCT) based on spectrum-slicing of a broadband source

This paper reports the characterization of a novel daisy-chained multi-channel optical coherence tomography (MC-OCT) method capable of concurrent scanning at multiple sites along the sample arm length of a low coherence interferometer. For this study, a cascade of two wavelength-based beam splitters is used to split the sample arm beam into three channels, forming three imaging (sensing) units. Channel-specific free-space beam paths are introduced in the sample arm to ensure equal optical path lengths amongst the different sensing beams, and hence, a single reference reflector is employed for simultaneous interrogation of signals reflected from samples (or from different spots of a sample). Realistic simulation is carried out to study the properties of the interference patterns such as axial resolutions and spurious side-lobes. Using a broadband light source of 50 nm bandwidth at 840 nm centre wavelength, the achieved axial resolutions of 24.23 µm, 17.81 µm and 20.49 µm for channels 1, 2 and 3, respectively, are in good correlation with simulations. Experimental results on a 3D-printed phantom further validate the imaging functionality of the system. The findings demonstrate a new single source and single interferometric-based MC-OCT method that can feasibly improve the transverse-scan throughput of conventional OCT.

Simultaneous dual-band line-field confocal optical coherence tomography: application to skin imaging.

Line-field confocal optical coherence tomography (LC-OCT) operating in two distinct spectral bands centered at 770 nm and 1250 nm is reported, using a single supercontinuum light source and two different line-scan cameras. B-scans are acquired simultaneously in the two bands at 4 frames per second. Greyscale representation and color fusion of the images are performed to either produce a single image with both high resolution (1.3 µm × 1.2 µm, lateral × axial, measured at the surface) in the superficial part of the image and deep penetration, or to highlight the spectroscopic properties of the sample. In vivo images of fair and dark skin are presented with a penetration depth of ∼700 µm.

Developing Tamoxifen-Based Chemical Probes for Use with a Dual-Modality Fluorescence and Optical Coherence Tomography Imaging Needle

Fluorescent small molecules based on the chemotherapeutic tamoxifen have been synthesised for use with an imaging needle capable of acquiring simultaneous fluorescence and optical coherence tomography (OCT) images. The chemical probes are based on the active metabolite of the drug, 4-hydroxytamoxifen that is coupled with a diamine linker to commercially available Alexa Fluor or 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes. The tamoxifen derivatives were then added to cultures of live oestrogen receptor positive MCF-7 human breast cancer cells and imaged using the miniaturised fibre-optic device enclosed within a 23-gauge needle (outer diameter 640 μm). The OCT images showed the micro-architecture of the cell culture, while the fluorescence identified oestrogen receptor positive cells. Both dyes were found to have suitable excitation and emission properties and are good candidates to further develop as probes for fluorescence-guided surgery.

A two-year study of diffused retinal pigment epitheliopathy treated with half-dose photodynamic therapy guided by simultaneous angiography and optical coherence tomography

ObjectivesDiffused retinal pigment epitheliopathy (DRPE) is not necessarily the same as chronic central serous chorioretinopathy (CSC), but a severe subgroup under the umbrella of chronic CSC. This study was to evaluate the efficacy and safety of half-dose PDT treating DRPE.MethodsA retrospective case series design was used. Forty-eight consecutive patients (48 eyes) with DRPE treated with half-dose PDT underwent follow-up at baseline, 3 months, 6 months, 12 months and 24 months. Simultaneous FA, ICGA and OCT were used for the treatment and follow-up. The primary outcomes were the subretinal fluid and best-corrected visual acuity in optical coherence tomography.ResultsComplete fluid absorption was achieved in 95.8% of eyes at 3 months and 100.0% of eyes at 24 months. The baseline logarithm of the minimum angle of resolution (logMAR) BCVA, which was 0.51 ± 0.36, significantly improved to 0.43 ± 0.38 (p < 0.001) at 6 months. The boost continued to 0.29 ± 0.37 (p < 0.001) at 12 months and 0.19 ± 0.39 (p < 0.001) at 24 months. The integrities of the ellipsoid zone (EZ) and interdigitation zone (IZ) improved throughout. Regression analyses showed the BCVA in logMAR was inversely correlated with the EZ (p < 0.01) and IZ (p < 0.01). The recurrence rate was 6.3%. No severe complications were witnessed.ConclusionsIn 48 eyes with DRPE, simultaneous angiography and OCT facilitated a more comprehensive guidance for half-dose PDT treatment and follow-up. The BCVA improvement occurred at 6 months, which may be attributed to the restoration of the outer retinal structure.

Endoscopic optical coherence tomography with wide field-of-view for the morphological and functional assessment of the human tympanic membrane.

.An endoscopic optical coherence tomography (OCT) system with a wide field-of-view of 8 mm is presented, which combines the image capability of endoscopic imaging at the middle ear with the advantages of functional OCT imaging, allowing a morphological and functional assessment of the human tympanic membrane. The endoscopic tube has a diameter of 3.5 mm and contains gradient-index optics for simultaneous forward-viewing OCT and video endoscopy. The endoscope allows the three-dimensional visualization of nearly the entire tympanic membrane. In addition, the oscillation of the tympanic membrane is measured spatially resolved and in the frequency range between 500 Hz and 5 kHz with 125 Hz resolution, which is realized by phase-resolved Doppler OCT imaging during acoustical excitation with chirp signals. The applicability of the OCT system is demonstrated in vivo. Due to the fast image acquisition, structural and functional measurements are only slightly affected by motion artifacts.

An imaging system integrating optical coherence tomography and interferometry for in vivo measurement of the thickness and dynamics of the tear film

BackgroundThe outermost layer of the tear film consists of a thin lipid layer (LL). The lipid layer serves as a barrier against evaporation of the aqueous component of the tear film. The ability to simultaneously image both the lipid layer thickness and overall tear film thickness is novel, and will help further understandings of mechanisms of how the lipid layer assembles and interacts with the full tear film thickness.MethodsWe developed a system that combines simultaneous optical coherence tomography (OCT) and thickness dependent fringes (TDF) interferometry for in vivo imaging of the tear film. The OCT possesses an axial resolution of 1.38 µm in tear film, providing an accurate measurement of the thickness of the overall tear film. The TDF can detect a minimal change of approximately 15 nm in LL thickness. In addition, the spatial resolution of TDF images in x–y plane is 5 µm.ResultsThe effect of instilling artificial tears on the PCTF and PLTF was examined. In both contact lens and non-contact lens wear, it could be observed from the OCT results that instillation of artificial tears increased the thickness of the overall tear film immediately, followed by a gradual reduction thereafter. These findings were consistent with other studies. However, unlike those previous reports, the thickness of the LL in this study was quantified simultaneously with the TDF subsystem. The results showed that bulking agents such as these artificial tears were not necessarily intended to increase the LL thickness. Immediately after instillation of artificial tears, the PCTF increased from 4.4 ± 0.97 to 20.3 ± 3.6 µm. The PCTF then decreased to 8.8 ± 2.1 µm at 4 min post-instillation. The thicknesses of the LL were 62.4 ± 14.5 nm, 48.7 ± 5.3 nm, and 55.2 ± 9.8 nm at pre-drop instillation, post-drop instillation, and 4-min post-drop instillation, respectively.ConclusionsIn this work, we have described a novel imaging system that integrated OCT and TDF imaging techniques, which may facilitate the study of many physiological and clinical aspects of the tear film.

Short-term Efficacy of Micropulse Yellow Laser in Non-center-involving Diabetic Macular Edema: Preliminary Results.

Objectives:The aim of this study was to evaluate the efficacy of micropulse yellow laser (MPL) on best corrected visual acuity (BCVA) and retinal thickness in patients with non-center-involving diabetic macular edema (DME).Materials and Methods:We retrospectively reviewed 9 eyes of 8 patients with non-center-involving DME who underwent MPL treatment between January 2015 and December 2016. BCVA (logMAR) and retinal thickness were evaluated before and 3 months after treatment. Maximum retinal thickness was determined manually from simultaneous spectral-domain optical coherence tomography images and recorded. The change in the measurements from before to after treatment was analyzed statistically.Results:Of the 8 patients, 3 were female and 5 were male. The mean age was 52.8 years. Two of the 9 eyes had received previous intravitreal anti-vascular endothelial growth factor injection(s). Median BCVA was improved 3 months after treatment, although the difference was not statistically significant (0.34 logMAR before and 0.29 logMAR after treatment). BCVA was improved in 4 eyes while it showed no change in the remaining 5 eyes. The mean retinal thickness was 470.6 μm at baseline and 416 μm at 3 months after MPL treatment (p=0.01). Retinal thickness decreased in all eyes after treatment.Conclusion:In this study, parafoveal retinal thickness showed significant decrease after MPL treatment in patients with DME. The limited increase in BCVA may be due to the inclusion of a low number of patients and only those with non-center-involving macular edema. MPL may be used as an alternative to conventional argon laser in non-center-involving DME.

Visible light OCT-based quantitative imaging of lipofuscin in the retinal pigment epithelium with standard reference targets.

We developed a technology for quantitative retinal autofluorescence (AF, or FAF for fundus AF) imaging for quantifying lipofuscin in the retinal pigment epithelium (RPE). The technology is based on simultaneous visible light optical coherence tomography (VIS-OCT) and AF imaging of the retina and a pair of reference standard targets at the intermediate retinal imaging plane with known reflectivity for the OCT and fluorescence efficiency for the FAF. The technology is able to eliminate the pre-RPE attenuation in FAF imaging by using the simultaneously acquired VIS-OCT image. With the OCT and fluorescence images of the reference targets, the effects of illumination power and detector sensitivity can be eliminated.

Miniaturized single-fiber-based needle probe for combined imaging and sensing in deep tissue.

The ability to visualize structure while simultaneously measuring chemical or physical properties of a biological tissue has the potential to improve our understanding of complex biological processes. We report the first miniaturized single-fiber-based imaging+sensing probe capable of simultaneous optical coherence tomography (OCT) imaging and temperature sensing. An OCT lens is fabricated at the distal end of a double-clad fiber, including a thin layer of rare-earth-doped tellurite glass to enable temperature measurements. The high refractive index of the tellurite glass enables a common-path interferometer configuration for OCT, allowing easy exchange of probes for biomedical applications. The simultaneous imaging+sensing capability is demonstrated on rat brains.