光学相干层析成像技术在内窥镜中的应用

光学相干层析成像(optical coherence tomography,OCT)技术是继X射线成像、核磁共振成像、超声成像等之后的一种新型的成像技术,其可光纤化的特点使得它易于医用电子内窥镜相结合。OCT内窥镜技术可实现对人体内部器官的高速率、高分辨率、无损伤、实时成像。主要介绍了OCT技术的种类、基本原理以及包括探测深度和纵向分辨率等的参数;简述了OCT内窥镜的发展历史以及最新成果,重点分析了光源对OCT内窥镜的影响。总结了OCT内窥镜的主要应用。     

A feasibility study of OCT for anatomical and vascular phenotyping of mouse embryo

The embryo phenotyping of genetic murine model is invaluable when investigating functions of genes underlying embryonic development and birth defect. Although traditional imaging technologies such as ultrasound are very useful for evaluating phenotype of murine embryos, the use of advanced techniques for phenotyping is desirable to obtain more information from genetic research. This letter tests the feasibility of optical coherence tomography (OCT) as a high‐throughput phenotyping tool for murine embryos. Three‐dimensional OCT imaging is performed for live and cleared mouse embryos in the late developmental stage (embryonic day 17.5). By using a dynamic focusing method and OCT angiography (OCTA) approach, our OCT imaging of the embryo exhibits rapid and clean visualization of organ structures deeper than 5 mm and complex microvasculature of perfused blood vessels in the murine embryonic body. This demonstration suggests that OCT imaging can be useful for comprehensively assessing embryo anatomy and angiography of genetically engineered mice.     

Multicontrast endomyocardial imaging by single‐channel high‐resolution cross‐polarization optical coherence tomography

A single‐channel high‐resolution cross‐polarization (CP) optical coherence tomography (OCT) system is presented for multicontrast imaging of human myocardium in one‐shot measurement. The intensity and functional contrasts, including the ratio between the cross‐ and co‐polarization channels as well as the cumulative retardation, are reconstructed from the CP‐OCT readout. By comparing the CP‐OCT results with histological analysis, it is shown that the system can successfully delineate microstructures in the myocardium and differentiate the fibrotic myocardium from normal or ablated myocardium based on the functional contrasts provided by the CP‐OCT system. The feasibility of using A‐line profiles from the 2 orthogonal polarization channels to identify fibrotic myocardium, normal myocardium and ablated lesion is also discussed.      

Noninvasive multimodal imaging by integrating optical coherence tomography with autofluorescence imaging for dental applications

We report the development of an integrated multifunctional imaging system capable of providing anatomical (optical coherence tomography, OCT), functional (OCT angiography, OCTA) and molecular imaging (light‐induced autofluorescence, LIAF) for in vivo dental applications. Blue excitation light (405 nm) was used for LIAF imaging, while the OCT was powered by a 1310 nm swept laser source. A red‐green‐blue digital camera, with a 450 nm cut‐on broadband optical filter, was used for LIAF detection. The exciting light source and camera were integrated directly with the OCT scanning probe. The integrated system used two noninvasive imaging modalities to improve the speed of in vivo OCT data collection and to better target the regions of interest. The newly designed system maintained the ability to detect differences between healthy and hypomineralized teeth, identify dental biofilm and visualize the microvasculature of gingival tissue. The development of the integrated OCT‐LIAF system provides an opportunity to conduct clinical studies more efficiently, examining changes in oral conditions over time.     

Super‐achromatic optical coherence tomography capsule for ultrahigh‐resolution imaging of esophagus

Endoscopic optical coherence tomography (OCT) is a noninvasive technology allowing for imaging of tissue microanatomies of luminal organs in real time. Conventional endoscopic OCT operates at 1300 nm wavelength region with a suboptimal axial resolution limited to 8‐20 μm. In this paper, we present the first ultrahigh‐resolution tethered OCT capsule operating at 800 nm and offering about 3‐ to 4‐fold improvement of axial resolution (plus enhanced imaging contrast). The capsule uses diffractive optics to manage chromatic aberration over a full ~200 nm spectral bandwidth centering around 830 nm, enabling to achieve super‐achromaticity and an axial resolution of ~2.6 μm in air. The performance of the OCT capsule is demonstrated by volumetric imaging of swine esophagus ex vivo and sheep esophagus in vivo, where fine anatomic structures including the sub‐epithelial layers are clearly identified. The ultrahigh resolution and excellent imaging contrast at 800 nm of the tethered capsule suggest the potential of the technology as an enabling tool for surveillance of early esophageal diseases on awake patients without the need for sedation.      

Flexible wide‐field optical micro‐angiography based on Fourier‐domain multiplexed dual‐beam swept source optical coherence tomography

Wide‐field optical coherence tomography angiography (OCTA) is gaining interest in clinical imaging applications. In this pursuit, it is challenging to maintain the imaging resolution and sensitivity throughout the wide field of view (FoV). Here, we propose a novel method/system of dual‐beam arrangement and Fourier‐domain multiplexing to achieve wide‐field OCTA when imaging the uneven surface samples. The proposed system provides 2 separate FoVs, with flexibility that the imaging area, focus of the imaging beam and imaging depth range can be individually adjusted for each FoV, leading to either (1) increased system imaging FoV or (2) capability of targeting 2 regions of interests that locate at depths with large difference between each other. We demonstrate this novel method by employing 100 kHz laser source in a swept source OCTA to achieve an effective 200 kHz sweeping rate, covering a 22 × 22 mm FoV. The results are verified by a SS‐OCTA system employing a 200 kHz laser source, together with the experimental demonstrations when imaging whole brain vasculature in rodent models and skin blood perfusion in human fingers, show‐casing the capability of proposed system to image live large samples with complex surface topography.      

TiO2‐coated fluoride nanoparticles for dental multimodal optical imaging

Core‐shell nanostructures associated with photonics techniques have found innumerous applications in diagnostics and therapy. In this work, we introduce a novel core‐shell nanostructure design that serves as a multimodal optical imaging contrast agent for dental adhesion evaluation. This nanostructure consists of a rare‐earth‐doped (NaYF₄:Yb 60%, Tm 0.5%)/NaYF₄ particle as the core (hexagonal prism, ~51 nm base side length) and the highly refractive TiO₂ material as the shell (~thickness of 15 nm). We show that the TiO₂ shell provides enhanced contrast for optical coherence tomography (OCT), while the rare‐earth‐doped core upconverts excitation light from 975 nm to an emission peaked at 800 nm for photoluminescence imaging. The OCT and the photoluminescence wide‐field images of human tooth were demonstrated with this nanoparticle core‐shell contrast agent. In addition, the described core‐shell nanoparticles (CSNps) were dispersed in the primer of a commercially available dental bonding system, allowing clear identification of dental adhesive layers with OCT. We evaluated that the presence of the CSNp in the adhesive induced an enhancement of 67% scattering coefficient to significantly increase the OCT contrast. Moreover, our results highlight that the upconversion photoluminescence in the near‐infrared spectrum region is suitable for image of deep dental tissue.      

MEMS-Based Handheld Fourier Domain Doppler Optical Coherence Tomography for Intraoperative Microvascular Anastomosis Imaging

Purpose

To demonstrate the feasibility of a miniature handheld optical coherence tomography (OCT) imager for real time intraoperative vascular patency evaluation in the setting of super-microsurgical vessel anastomosis.

Methods

A novel handheld imager Fourier domain Doppler optical coherence tomography based on a 1.3-µm central wavelength swept source for extravascular imaging was developed. The imager was minimized through the adoption of a 2.4-mm diameter microelectromechanical systems (MEMS) scanning mirror, additionally a 12.7-mm diameter lens system was designed and combined with the MEMS mirror to achieve a small form factor that optimize functionality as a handheld extravascular OCT imager. To evaluate in-vivo applicability, super-microsurgical vessel anastomosis was performed in a mouse femoral vessel cut and repair model employing conventional interrupted suture technique as well as a novel non-suture cuff technique. Vascular anastomosis patency after clinically successful repair was evaluated using the novel handheld OCT imager.

Results

With an adjustable lateral image field of view up to 1.5 mm by 1.5 mm, high-resolution simultaneous structural and flow imaging of the blood vessels were successfully acquired for BALB/C mouse after orthotopic hind limb transplantation using a non-suture cuff technique and BALB/C mouse after femoral artery anastomosis using a suture technique. We experimentally quantify the axial and lateral resolution of the OCT to be 12.6 µm in air and 17.5 µm respectively. The OCT has a sensitivity of 84 dB and sensitivity roll-off of 5.7 dB/mm over an imaging range of 5 mm. Imaging with a frame rate of 36 Hz for an image size of 1000(lateral)×512(axial) pixels using a 50,000 A-lines per second swept source was achieved. Quantitative vessel lumen patency, lumen narrowing and thrombosis analysis were performed based on acquired structure and Doppler images.

Conclusions

A miniature handheld OCT imager that can be used for intraoperative evaluation of microvascular anastomosis was successfully demonstrated.     

Depth‐resolved multimodal imaging: Wavelength modulated spatially offset Raman spectroscopy with optical coherence tomography

A major challenge in biophotonics is multimodal imaging to obtain both morphological and molecular information at depth. We demonstrate a hybrid approach integrating optical coherence tomography (OCT) with wavelength modulated spatially offset Raman spectroscopy (WM‐SORS). With depth colocalization obtained from the OCT, we can penetrate 1.2‐mm deep into strong scattering media (lard) to acquire up to a 14‐fold enhancement of a Raman signal from a hidden target (polystyrene) with a spatial offset. Our approach is capable of detecting both Raman and OCT signals for pharmaceutical particles embedded in turbid media and revealing the white matter at depth within a 0.6‐mm thick brain tissue layer. This depth resolved label‐free multimodal approach is a powerful route to analyze complex biomedical samples.      

Two optical coherence tomography systems detect topical gold nanoshells in hair follicles,sweat ducts and measure epidermis

Optical coherence tomography (OCT) is an established imaging technology for in vivo skin investigation. Topical application of gold nanoshells (GNS) provides contrast enhancement in OCT by generating a strong hyperreflective signal from hair follicles and sweat glands, which are the natural skin openings. This study explores the utility of 150 nm diameter GNS as contrast agent for OCT imaging. GNS was massaged into skin and examined in four skin areas of 11 healthy volunteers. A commercial OCT system and a prototype with 3 μm resolution (UHR‐OCT) were employed to detect potential benefits of increased resolution and variability in intensity generated by the GNS. In both OCT‐systems GNS enhanced contrast from hair follicles and sweat ducts. Highest average penetration depth of GNS was in armpit 0.64 mm ± SD 0.17, maximum penetration depth was 1.20 mm in hair follicles and 15 to 40 μm in sweat ducts. Pixel intensity generated from GNS in hair follicles was significantly higher in UHR‐OCT images (P = .002) and epidermal thickness significantly lower 0.14 vs 0.16 mm (P = .027). This study suggests that GNSs are interesting candidates for increasing sensitivity in OCT diagnosis of hair and sweat gland disorders and demonstrates that choice of OCT systems influences results.      

A spatial resolution evaluation method of endoscopic optical coherence tomography system using the annular phantom

As an important biomedical imaging method, endoscopic optical coherence tomography (OCT) is necessary to check its performance regularly. The ordinary plane phantoms are only able to evaluate part of image tangent to the probe. In this research, a spatial resolution estimate method of the endoscope OCT system is proposed. The annular phantom, made by uniformly distributing golden scattered microparticles in polydimethylsiloxane (PDMS), can provide dynamic scanning imaging evaluation of endoscopic OCT system, closer to its actual working status. The point spread function analysis method is used to analyze the imaging results of the annular phantom with the endoscopic OCT system. And many scattered particles are statistically analyzed to determine the spatial resolution of the endoscope OCT system. The method is low in cost, simple and convenient. It is valuable for the development of test standards for endoscope OCT systems.     

Spectrally encoded coherence tomography and reflectometry: Simultaneous en face and cross‐sectional imaging at 2 gigapixels per second

Non‐invasive biological imaging is crucial for understanding in vivo structure and function. Optical coherence tomography (OCT) and reflectance confocal microscopy are two of the most widely used optical modalities for exogenous contrast‐free, high‐resolution, three‐dimensional imaging in non‐fluorescent scattering tissues. However, sample motion remains a critical barrier to raster‐scanned acquisition and reconstruction of wide‐field anatomically accurate volumetric datasets. We introduce spectrally encoded coherence tomography and reflectometry (SECTR), a high‐speed, multimodality system for simultaneous OCT and spectrally encoded reflectance (SER) imaging. SECTR utilizes a robust system design consisting of shared optical relays, scanning mirrors, swept laser and digitizer to achieve the fastest reported in vivo multimodal imaging rate of 2 gigapixels per second. Our optical design and acquisition scheme enable spatiotemporally co‐registered acquisition of OCT cross‐sections simultaneously with en face SER images for multivolumetric mosaicking. Complementary axial and lateral translation and rotation are extracted from OCT and SER data, respectively, for full volumetric estimation of sample motion with micron spatial and millisecond temporal resolution.      

In vivo monitoring the dynamic process of acute retinal hemorrhage and repair in zebrafish with spectral‐domain optical coherence tomography

Retina, the only light sensor in the human eye, is hidden and extremely fragile. Optimized animal models and efficient imaging techniques are very important for the study of retinopathy. In this work, the rapid retinal injury process and the long‐term retinal repair process were in vivo continuously evaluated with a novel imaging technology spectral‐domain optical coherence tomography (SD‐OCT) in a unique animal model zebrafish. Acute retinal injury was constructed on adult zebrafish by needle injection surgery. SD‐OCT imaging was carried out immediately after the mechanical injury. The retinal hemorrhage, which lasted only 5 seconds, could be visualized dynamically by SD‐OCT. The process of blood clearance and retinal repair was also evaluated because SD‐OCT imaging is nondestructive. Both SD‐OCT imaging results and behavioral analyzing results demonstrated that zebrafish retina could be repaired by itself within 15 days, which was confirmed by the results of pathological experiment.     

Comparative study of optical coherence tomography angiography algorithms for rodent retinal imaging

Optical coherence tomography angiography (OCTA) is a functional extension of optical coherence tomography for non-invasive in vivo three-dimensional imaging of the microvasculature of biological tissues. Several algorithms have been developed to construct OCTA images from the measured optical coherence tomography signals. In this study, we compared the performance of three OCTA algorithms that are based on the variance of phase, amplitude, and the complex representations of the optical coherence tomography signals for rodent retinal imaging, namely the phase variance, improved speckle contrast, and optical microangiography. The performance of the different algorithms was evaluated by comparing the quality of the OCTA images regarding how well the vasculature network can be resolved. Quantities that are widely used in ophthalmic studies including blood vessel density, vessel diameter index, vessel perimeter index, vessel complexity index were also compared. Results showed that both the improved speckle contrast and optical microangiography algorithms are more robust than phase variance, and they can reveal similar vasculature features while there are statistical differences in the calculated quantities.     

Jones matrix‐based speckle‐decorrelation angiography using polarization‐sensitive optical coherence tomography

We show that polarization‐sensitive optical coherence tomography angiography (PS‐OCTA) based on full Jones matrix assessment of speckle decorrelation offers improved contrast and depth of vessel imaging over conventional OCTA. We determine how best to combine the individual Jones matrix elements and compare the resulting image quality to that of a conventional OCT scanner by co‐locating and imaging the same skin locations with closely matched scanning setups. Vessel projection images from finger and forearm skin demonstrate the benefits of Jones matrix‐based PS‐OCTA. Our study provides a promising starting point and a useful reference for future pre‐clinical and clinical applications of Jones matrix‐based PS‐OCTA.     

Optical coherence hyperspectral microscopy with a single supercontinuum light source

In the paper, we have developed an optical coherence hyperspectral microscopy with a single supercontinuum light source. The microscopy consists of optical coherence tomography (OCT) and hyperspectral imaging (HSI), which can visualize the structural and functional characteristics of biological tissues. The 500 to 700 nm band is selected for HSI and OCT imaging, where HSI enables imaging of oxygen saturation and hemoglobin (Hb) content, while OCT acquires structural characteristics to assess the morphology of biological tissues. The system performance of the optical coherence hyperspectral microscopy is verified by normal mice ears, and the practical applications of the microscopy is further performed in 4T1 and inflammation Balb/c mice ears in vivo. The experimental results demonstrate that the microscopy has potential to provide complementary information for clinical applications.     

Three‐dimensional mapping of the attenuation coefficient in optical coherence tomography to enhance breast tissue microarchitecture contrast

Effective intraoperative tumor margin assessment is needed to reduce re‐excision rates in breast‐conserving surgery (BCS). Mapping the attenuation coefficient in optical coherence tomography (OCT) throughout a sample to create an image (attenuation imaging) is one promising approach. For the first time, three‐dimensional OCT attenuation imaging of human breast tissue microarchitecture using a wide‐field (up to ~45 × 45 × 3.5 mm) imaging system is demonstrated. Representative results from three mastectomy and one BCS specimen (from 31 specimens) are presented with co‐registered postoperative histology. Attenuation imaging is shown to provide substantially improved contrast over OCT, delineating nuanced features within tumors (including necrosis and variations in tumor cell density and growth patterns) and benign features (such as sclerosing adenosis). Additionally, quantitative micro‐elastography (QME) images presented alongside OCT and attenuation images show that these techniques provide complementary contrast, suggesting that multimodal imaging could increase tissue identification accuracy and potentially improve tumor margin assessment.     

Polarization‐multiplexed,dual‐beam swept source optical coherence tomography angiography

A polarization‐multiplexed, dual‐beam setup is proposed to expand the field of view (FOV) for a swept source optical coherence tomography angiography (OCTA) system. This method used a Wollaston prism to split sample path light into 2 orthogonal‐polarized beams. This allowed 2 beams to shine on the cornea at an angle separation of ~14°, which led to a separation of ~4.2 mm on the retina. A 3‐mm glass plate was inserted into one of the beam paths to set a constant path length difference between the 2 polarized beams so the interferogram from the 2 beams are coded at different frequency bands. The resulting OCTA images from the 2 beams were coded with a depth separation of ~2 mm. A total of 5 × 5 mm² angiograms from the 2 beams were obtained simultaneously in 4 seconds. The 2 angiograms then were montaged to get a wider FOV of ~5 × 9.2 mm².      

Ex vivo investigations on the potential of optical coherence tomography (OCT) as a diagnostic tool for reproductive medicine in a bovine model

Routine infertility investigations in the male and female include imaging techniques such as ultrasonography and endoscopy (fertiloscopy). However, these techniques lack the resolution to localize vital sperm or to reveal detailed morphological analysis of the oviduct which is often the cause of infertility in females. Therefore we set out to evaluate the efficiency of optical coherence tomography (OCT) as a diagnostic imaging tool for micron‐scale visualization of the male and female genital tract. Using the bovine as a model, the optical features of the Telesto^TM, Ganymede^TM (both Thorlabs) and Niris^TM (Imalux) OCT imaging systems were compared.

Comparative visualization of ex vivo bovine testicular tissue by the Telesto^TM microscopic optical coherence tomography system (left) and corresponding H&E staining (right).