Multi-functional Optical Coherence Tomography Research Articles

Multifunctional adaptive optics optical coherence tomography allows cellular scale reflectometry, polarimetry, and angiography in the living human eye.

Clinicians are unable to detect glaucoma until substantial loss or dysfunction of retinal ganglion cells occurs. To this end, novel measures are needed. We have developed an optical imaging solution based on adaptive optics optical coherence tomography (AO-OCT) to discern key clinical features of glaucoma and other neurodegenerative diseases at the cellular scale in the living eye. Here, we test the feasibility of measuring AO-OCT-based reflectance, retardance, optic axis orientation, and angiogram at specifically targeted locations in the living human retina and optic nerve head. Multifunctional imaging, combined with focus stacking and global image registration algorithms, allows us to visualize cellular details of retinal nerve fiber bundles, ganglion cell layer somas, glial septa, superior vascular complex capillaries, and connective tissues. These are key histologic features of neurodegenerative diseases, including glaucoma, that are now measurable in vivo with excellent repeatability and reproducibility. Incorporating this noninvasive cellular-scale imaging with objective measurements will significantly enhance existing clinical assessments, which is pivotal in facilitating the early detection of eye disease and understanding the mechanisms of neurodegeneration.

Information-Rich Multi-Functional OCT for Adult Zebrafish Intra- and Extracranial Imaging.

The zebrafish serves as a valuable animal model for both intra- and extracranial research, particularly in relation to the brain and skull. To effectively investigate the development and regeneration of adult zebrafish, a versatile in vivo imaging technique capable of showing both intra- and extracranial conditions is essential. In this paper, we utilized a high-resolution multi-functional optical coherence tomography (OCT) to obtain rich intra- and extracranial imaging outcomes of adult zebrafish, encompassing pigmentation distribution, tissue-specific information, cranial vascular imaging, and the monitoring of traumatic brain injury (TBI). Notably, it is the first that the channels through the zebrafish cranial suture, which may have a crucial function in maintaining the patency of the cranial sutures, have been observed. Rich imaging results demonstrated that a high-resolution multi-functional OCT system can provide a wealth of novel and interpretable biological information for intra- and extracranial studies of adult zebrafish.

Development of Intraoperatively Assisted Robot Diagnostic System of Orthopedic Surgery using Multi-functional OCT

Development of Intraoperatively Assisted Robot Diagnostic System of Orthopedic Surgery using Multi-functional OCT

Evaluation on Micro-biomechanical Diagnosing System of Early OA using Multi-functional OCT

Evaluation on Micro-biomechanical Diagnosing System of Early OA using Multi-functional OCT

Evaluation on Micro-biomechanical Diagnosing System of Human Skin using Multi-functional OCT

Evaluation on Micro-biomechanical Diagnosing System of Human Skin using Multi-functional OCT

In Vivo Longitudinal Tracking of Lymphangiogenesis and Angiogenesis in Cutaneous Melanoma Mouse Model Using Multifunctional Optical Coherence Tomography

Melanoma is a high-risk skin cancer because it tends to metastasize early and ultimately leads to death. In this study, we introduced a noninvasive multifunctional optical coherence tomography (MFOCT) for the early detection of premetastatic pathogenesis in cutaneous melanoma by label-free imaging of microstructures (i.e., providing the thickness and the scattering information) and microcirculation (i.e., providing depth-resolved angiography and lymphangiography). Using MFOCT-based approaches, we presented an in vivo longitudinal observation of the tumor microenvironment in BrafV600E/V600E;Pten−/− mice with inducible melanoma monitored for 42 days. Quantitative analysis of MFOCT images identified an increased number of lymphatic and vascular vessels during tumor progression and faster lymphangiogenesis (beginning on day 21) than angiogenesis (beginning on day 28) in the melanoma microenvironment. We further observed lymphatic vessel enlargement from the first week of melanoma development, implying tumor cells interacting with the vessels and increased likelihood of metastasis. MFOCT identified cutaneous melanoma‒associated angiogenesis and lymphangiogenesis before the possible visual perception of the tumor (≥42 days) and before metastasis could be diagnosed using micropositron emission tomography (35 days). Thus, the proposed quantitative analysis using MFOCT has the potential for early detection of cutaneous melanoma progression or prediction of metastatic melanoma in a mouse model. However, retrospective and extensive experiments still need to be performed in the future to confirm the value of MFOCT in clinical application.

Novel carbazole-based multifunctional materials with a hybridized local and charge-transfer excited state acting as deep-blue emitters and phosphorescent hosts for highly efficient organic light-emitting diodes

Two novel multifunctional HLCT materials, namely OCI and OCT, were presented and they proved to be better green hosts than CBP. Acting as a deep-blue emitter, the OCI-based device achieved an EQE of 5.06% and CIEy < 0.04 with an EL peak at 424 nm.

Optical Coherence Tomography Findings in the Retinas of SOD1 Knockout Mice.

PurposeThe retinal phenotype of popular mouse models mimicking ophthalmic diseases, such as the superoxide dismutase 1 (SOD1) knockout (KO) mouse model, has mainly been assessed by ex vivo histology and in vivo fundus photography. We used multifunctional optical coherence tomography (OCT) to characterize the retinas of SOD1 KO mice in vivo.MethodsThe custom-made ophthalmoscope featured a combination of conventional OCT, polarization-sensitive OCT, and OCT angiography. Seven SOD1 KO mice and nine age-matched controls were imaged between 6 and 17 months of age. A postprocessing framework was used to analyze total and outer retinal thickness changes. Drusenlike lesions were segmented, and their sizes and the number of lesions were assessed quantitatively. Their appearance in the conventional reflectivity images, as well as in the corresponding polarization-sensitive images, was characterized qualitatively.ResultsDrusenlike lesions increased in size and number with age for SOD1 KO mice. Exploiting the multiple contrast channels, the appearance of the lesions was found to resemble pseudodrusen observed in eyes of patients suffering from dry age-related macular degeneration. The total and outer retinal thicknesses were lower on average after 11 months and 7 months in SOD1 KO mice compared with age-matched controls. Neovascularizations were found in one out of seven KO animals.ConclusionsOCT imaging proved beneficial for a detailed in vivo characterization of the pathological changes in SOD1 KO mice.Translational RelevancePhenotyping of animal models using modern imaging concepts can be conducted with more precision and might also ease the translation of conclusions between clinical and preclinical research.

In vivoendoscopic multifunctional optical coherence tomography imaging of lungs periphery before and after bronchial thermoplasty

We demonstrate the use of a motorized distal scanning endoscope to acquirein vivodata in lungs of severe-asthma patients before and after an asthma treatment procedure called bronchial thermoplasty. Conventional optical coherence tomography (OCT) intensity images and polarisation sensitive OCT images were extracted from the acquired data. PS-OCT endoscopy allowing the visualization and segmentation of airway smooth muscle layer - which plays a key role in bronchoconstriction during asthma attacks - showed its potential as means to evaluate the effectiveness of bronchial thermoplasty.

Clinical multi-functional OCT for retinal imaging.

A compact clinical prototype multi-functional optical coherence tomography (OCT) device for the posterior human eye has been developed. This compact Jones-matrix OCT (JM-OCT) device integrates all components into a single package. Multiple image functions, i.e., scattering intensity, OCT angiography, and the degree of polarization uniformity, are obtained. The device has the capability for measuring local birefringence. Multi-functional imaging of several eyes with age-related macular degeneration is demonstrated. The compact JM-OCT device will be useful for the in vivo non-invasive investigation of abnormal tissues.

In vivo multifunctional optical coherence tomography at the periphery of the lungs.

Remodeling of tissue, such as airway smooth muscle (ASM) and extracellular matrix, is considered a key feature of airways disease. No clinically accepted diagnostic method is currently available to assess airway remodeling or the effect of treatment modalities such as bronchial thermoplasty in asthma, other than invasive airway biopsies. Optical coherence tomography (OCT) generates cross-sectional, near-histological images of airway segments and enables identification and quantification of airway wall layers based on light scattering properties only. In this study, we used a custom motorized OCT probe that combines standard and polarization sensitive OCT (PS-OCT) to visualize birefringent tissue in vivo in the airway wall of a patient with severe asthma in a minimally invasive manner. We used optic axis uniformity (OAxU) to highlight the presence of uniformly arranged fiber-like tissue, helping visualizing the abundance of ASM and connective tissue structures. Attenuation coefficient images of the airways are presented for the first time, showing superior architectural contrast compared to standard OCT images. A novel segmentation algorithm was developed to detect the surface of the endoscope sheath and the surface of the tissue. PS-OCT is an innovative imaging technique that holds promise to assess airway remodeling including ASM and connective tissue in a minimally invasive, real-time manner.

In Vivo Characterization of Spontaneous Retinal Neovascularization in the Mouse Eye by Multifunctional Optical Coherence Tomography.

To investigate the early development of spontaneous retinal neovascularization in the murine retina by a multifunctional optical coherence tomography approach. To characterize involved tissue changes in vivo and describe structural and functional changes over time. A multifunctional optical coherence tomography (OCT) system providing 3-fold contrast comprising reflectivity, polarization sensitivity, and OCT angiography (OCTA) was utilized to image very-low-density lipoprotein receptor (VLDLR) knockout mice. Baseline measurements were acquired as early as postnatal day 14 and a follow-up of neovascularization development was performed until the age of 3 months. Control mice were imaged accordingly and a multiparametric image analysis was performed to characterize different stages of pathologic vascular growth. Histology was conducted at the endpoint of the experiment. An interventional pilot experiment was conducted to investigate the effect of the anti-vascular endothelial growth factor (VEGF) agent aflibercept on the development of retinal neovascularization. Onset of neovascularization was imaged at baseline, and significant changes were encountered in the retina over time, including reduced retinal thickness, increase of lesion volume, migration of pigmented structures, and presence of abnormal blood flow in the outer retina. Multifunctional image contrast was correlated to ex vivo histology. Microscopic analysis of retinal flat mounts and cross-sectional samples confirmed the changes observed in in vivo structural and functional OCT images. Administration of an anti-VEGF agent resulted in a significantly reduced lesion volume. Longitudinal, multifunctional OCT imaging of infant VLDLR-/- mouse retinas enabled a multiparametric, in vivo staging of neovascularization formation from before lesion onset until their manifestation.

Development of Micro-tomographic Visualization of Capillary Blood Flow Velocity and Viscoelastic Properties using Multi-Functional Optical Coherence Tomography

Development of Micro-tomographic Visualization of Capillary Blood Flow Velocity and Viscoelastic Properties using Multi-Functional Optical Coherence Tomography

Application of multi-functional OCT to the diagnosis of skin mechanics

Application of multi-functional OCT to the diagnosis of skin mechanics

Multifunctional in vivo imaging for monitoring wound healing using swept-source polarization-sensitive optical coherence tomography.

Wound healing involves a complex and dynamic biological process in response to tissue injury. Monitoring of the cascade of cellular events is useful for wound management and treatment. The aim of this study is to demonstrate the potential of multifunctional polarization-sensitive optical coherence tomography (PS-OCT) to longitudinally monitor the self-healing process in a murine cutaneous wound model. A multi-functional PS-OCT system based on swept source OCT configuration (1,310 nm central wavelength) was designed to obtain simultaneously microstructural, blood perfusion, and birefringent information of a biological tissue in vivo. A 1-mm-diameter wound was generated in a mouse pinna with a complete biopsy punch. Afterwards, the self-healing process of the injured tissue was observed every week over 6-week period using the multifunctional system to measure changes in the tissue birefringence. Further OCT angiography (OCTA) was used in post data processing to obtain blood perfusion information over the injured tissue. Three complementary images indicating the changes in anatomical, vascular, and birefringent information of tissue around wound were simultaneously provided from a 3-dimensional (3-D) PS-OCT data set during the wound repair over 1 month. Specifically, inflammatory and proliferative phases of wound healing were characterized by thickened epidermal tissue (from OCT images) and angiogenesis (from OCT angiography images) around wound. Also, it was observed that the regenerating tissues had highly realigned birefringent structures (from PS-OCT images). This preliminary study suggests that the proposed multi-functional imaging modality has a great potential to improve the understanding of wound healing through non-invasive, serial monitoring of vascular and tissue responses to injury. Lasers Surg. Med. 50:213-221, 2018. © 2017 Wiley Periodicals, Inc.

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).

Multifunctional OCT for preclincial imaging

SummaryFunctional extensions of optical coherence tomography (OCT) expand image contrast and enable quantitative measurements of optical tissue properties, improved segmentation of tissue morphology and the assessment of physiological parameters. In this presentation, we will discuss applications of multifunctional OCT including high‐resolution polarization‐sensitive OCT and OCT angiography for preclinical studies of ocular disease models.

Ocular fundus pulsations within the posterior rat eye: Chorioscleral motion and response to elevated intraocular pressure

A multi-functional optical coherence tomography (OCT) approach is presented to determine ocular fundus pulsations as an axial displacement between the retina and the chorioscleral complex in the albino rat eye. By combining optical coherence elastography and OCT angiography (OCTA), we measure subtle deformations in the nanometer range within the eye and simultaneously map retinal and choroidal perfusion. The conventional OCT reflectivity contrast serves as a backbone to segment the retina and to define several slabs which are subsequently used for quantitative ocular pulsation measurements as well as for a qualitative exploration of the multi-functional OCT image data. The proposed concept is applied in healthy albino rats as well as in rats under acute elevation of the intraocular pressure (IOP). The evaluation of this experiment revealed an increased pulsatility and deformation between the retinal and chorioscleral complex while increasing the IOP level from 15 mmHg to 65 mmHg. At IOP levels exceeding 65 mmHg, the pulsatility decreased significantly and retinal as well as choroidal perfusion vanished in OCTA. Furthermore, the evaluation of the multi-parametric experiment revealed a spatial correlation between fundus pulsatility and choroidal blood flow. This indicates that the assessed pulsatility may be a valuable parameter describing the choroidal perfusion.

Dermoscopy guided dark-field multi-functional optical coherence tomography.

Dermoscopy is a skin surface microscopic technique allowing specular reflection free observation of the skin, and has been used to examine pigmented skin lesions. However, dermoscopy has limitations in providing depth information due to lack of 3D resolution. In order to overcome the limitations, we developed dermoscopy guided multi-functional optical coherence tomography (MF-OCT) providing both high-contrast superficial information and depth-resolved structural, birefringent, and vascular information of the skin simultaneously. Dermoscopy and MF-OCT were combined by using a dichroic mirror, and dark-field configuration was adapted for MF-OCT to reduce specular reflection. After characterization, dermoscopy guided MF-OCT was applied to several human skin lesions such as the scar, port-wine stain (PWS) as well as the normal skin for demonstration. Various features of the scar and PWS were elucidated by both dermoscopy and MF-OCT. Dermoscopy guided MF-OCT may be useful for evaluation and treatment monitoring of skin lesions in clinical applications.

多機能ＯＣＴを用いたスキンメカニクス非侵襲マイクロ断層診断法の進展

多機能ＯＣＴを用いたスキンメカニクス非侵襲マイクロ断層診断法の進展