Deep-learning-based motion correction in optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) is a widely applied tool to image microvascular networks with high spatial resolution and sensitivity. Due to limited imaging speed, the artifacts caused by tissue motion can severely compromise visualization of the microvascular networks and quantification of OCTA images. In this article, we propose a deep-learning-based framework to effectively correct motion artifacts and retrieve microvascular architectures. This method comprised two deep neural networks in which the first subnet was applied to distinguish motion corrupted B-scan images from a volumetric dataset. Based on the classification results, the artifacts could be removed from the en face maximum-intensity-projection (MIP) OCTA image. To restore the disturbed vasculature induced by artifact removal, the second subnet, an inpainting neural network, was utilized to reconnect the broken vascular networks. We applied the method to postprocess OCTA images of the microvascular networks in mouse cortex in vivo. Both image comparison and quantitative analysis show that the proposed method can significantly improve OCTA image by efficiently recovering microvasculature from the overwhelming motion artifacts.     

Dynamic single gold nanoparticle visualization by clinical intracoronary optical coherence tomography

The potential use of Gold Nanoparticles (GNPs) as contrast agents for clinical intracoronary frequency domain Optical Coherence Tomography (OCT) is here explored. The OCT contrast enhancement caused by GNPs of different sizes and morphologies has been systematically investigated and correlated with their optical properties. Among the different GNPs commercially available with plasmon resonances close to the operating wavelength of intracoronary OCT (1.3 µm), Gold Nanoshells (GNSs) have provided the best OCT contrast due to their largest scattering cross section at this wavelength. Clinical intracoronary OCT catheters are here demonstrated to be capable of three dimensional visualization and real‐time tracking of individual GNSs. Results here included open an avenue to novel application of intravascular clinical OCT in combination with GNPs, such as real time evaluation of intravascular obstructions or pressure gradients.

     

Three‐dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology

A preliminary clinical trial using state‐of‐the‐art multiphoton tomography (MPT) and optical coherence tomography (OCT) for three‐dimensional (3D) multimodal in vivo imaging of normal skin, nevi, scars and pathologic skin lesions has been conducted. MPT enabled visualization of sub‐cellular details with axial and transverse resolutions of <2 μm and <0.5 μm, respectively, from a volume of 0.35 × 0.35 × 0.2 mm³ at a frame rate of 0.14 Hz (512 × 512 pixels). State‐of‐the‐art OCT, operating at a center wavelength of 1300 nm, was capable of acquiring 3D images depicting the layered architecture of skin with axial and transverse resolutions ～8 μm and ～20 μm, respectively, from a volume of 7 × 3.5 × 1.5 mm³ at a frame rate of 46 Hz (1024 × 1024 pixels). This study demonstrates the clinical diagnostic potential of MPT/OCT for pre‐screening relatively large areas of skin using 3D OCT to identify suspicious regions at microscopic level and subsequently using high resolution MPT to obtain zoomed in, sub‐cellular level information of the respective regions (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Quantitative evaluation of optical coherence tomography angiography images of diabetic retinopathy eyes before and after removal of projection artifacts

Projection artifacts (PAs) affect the quantification of vascular parameters in the deep layer optical coherence tomography (OCT) angiography image. This study eliminated PA and quantified its effect on imaging. 53 eyes (30 subjects) of normal Indian subjects and 113 eyes (92 patients) of type 2 diabetes mellitus with retinopathy (DR) underwent imaging with a scan area of 3 mm × 3 mm. In this study, a normalized cross‐correlation between superficial and deep layer was used to remove PA in deep layer. Local fractal analysis was done to compute vascular parameters such as foveal avascular zone area (mm²), vessel density (%), spacing between large vessels (%) and spacing between small vessels (%). Before PA removal, vessel density for mild nonproliferative (NPDR), moderate NPDR, severe NPDR and proliferative DR were 42.56 ±1.69%, 40.69 ±0.72%, 37.34 ±0.85% and 35.61 ±1.26%, respectively. After artifact removal, vessel density was 28.9 ±1.22%, 29.9 ±0.56%, 26.19 ±0.59% and 24.02 ±0.94%, respectively. All the vascular parameters were statistically significant (P <.001) between normal and disease eyes, irrespective of superficial and deep retinal layers. Parafoveal sectoral analyses showed that temporal zone had the lowest vessel density and may undergo DR‐related changes first. The current approach enabled rapid and accurate quantitative interpretation of DR eyes, without PA.      

Automated quantification of superficial retinal capillaries and large vessels for diabetic retinopathy on optical coherence tomographic angiography

Optical coherence tomography angiography (OCTA) is a relatively new technique with capillary‐level resolution, which has shown great potential for the diagnosis of diabetic retinopathy (DR). A fully automatic algorithm for the quantitative measurement of microcirculatory changes in sight‐threatening DR is presented. The foveal avascular zone (FAZ) segmentation was improved with a graph‐theoretic method and the large vessels and capillaries were separately identified and analyzed. The method was evaluated in healthy and diabetic eyes with various stages of retinopathy. Results showed that, compared with the healthy group, the diabetic group showed a significantly larger large vessel density, but a significantly smaller capillary density (P < .001). Circularity of FAZ was significantly smaller while nonperfusion area was significantly larger in the diabetic group. The combined variable of all image metrics reached an area under the ROC of 0.853 (95% CI, 0.784‐0.923) for mild to moderate nonproliferative DR and 0.950 (95% CI, 0.922‐0.979) for proliferative DR. Microvascular and FAZ changes with various DR stages can be accurately delineated using the developed automatic program. Quantitative metrics on OCTA serve as potential biomarkers for the staging of DR.     

Contrast‐enhanced optical coherence tomography for melanoma detection: An in vitro study

Optical coherence tomography (OCT), with a high‐spatial resolution (<10 microns), intermediate penetration depth (~1.5 mm) and volumetric imaging capability is a great candidate to be used as a diagnostic‐assistant modality in dermatology. At this time, the accuracy of OCT for melanoma detection is lower than anticipated. In this letter, we studied for the first time, the use of a novel contrast agent consist of ultra‐small nanoparticles conjugated to a melanoma biomarker to improve the accuracy of OCT for differentiation of melanoma cells from nonmelanoma cells, in vitro. We call this approach SMall nanoparticle Aggregation‐enhanced Radiomics of Tumor (SMART)‐OCT imaging. This initial proof of concept study is the first step toward the broad utilization of this method for high accuracy all types of tumor detection applications.     

1,25-Dihydroxyvitamin D3: A novel agent for enhancing wound healing

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃), has diverse effects in a variety of tissues and cell types, including skin. Since 1,25(OH)₂D₃ affects both fibroblast and keratinocytes, we evalauated the effect of 1,25(OH)₂D₃ or wound healing. We investigated the effect of the topically applied 1,25(OH)₂D₃ or vehicle on the healing of cutaneous wounds in rats in a blinded manner. Wound areas were measured by planimetry technique. Healing was expressed as the percentage of the original wound area that was healed. 1,25(OH)₂D₃ at concentrations between 5 and 50 ng/day caused a dose-dependent acceleration of healing. Time course and specificity studies indicated that 1,25(OH)₂D₃ specifically promoted healing between 1–5 days after wounding as compared with vitamin D (0.5 μg/day), which showed no significant improvement over control. Our results suggest that 1,25(OH)₂D₃ and its analogues may be a new class of compounds that could be developed to enhance wound healing. © 1995 Wiley-Liss, Inc.     

一种新型高通量三维脑细胞芯片的研制及农药神经毒性评价应用

为了模拟体内脑组织细胞的三维生长环境,高效开展脑疾病和有关药物的研究工作,文中设计和制造了一种新型高通量三维脑细胞芯片.芯片由多孔滤网和三维脑细胞颗粒构成,装载于常规的96孔细胞培养板上使用.多孔滤网和细胞颗粒模具采用计算机建模、3D打印阳模、琼脂糖-PDMS两次翻模等技术制造,三维脑细胞颗粒是将小鼠胚胎脑细胞与海藻酸...     

Real‐time in vivo imaging of adult Zebrafish brain using optical coherence tomography

We report noninvasive imaging of the brain of adult Zebrafish (Danio rerio) using real time optical coherence tomography (OCT) capable of acquiring cross sectional 2D OCT images @ 8 frames/sec. Anatomic features such as telencephalon, tectum opticum, eminentia Granularis and cerebellum were clearly resolved in the OCT images. A 3D model of Zebrafish brain was reconstructed, for the first time to our knowledge, using these 2D OCT images. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Three-dimensional segmentation and depth-encoded visualization of choroidal vasculature using swept-source optical coherence tomography

The choroid provides nutritional support for the retinal pigment epithelium and photoreceptors. Choroidal dysfunction plays a major role in several of the most important causes of vision loss including age-related macular degeneration, myopic degeneration, and pachychoroid diseases such as central serous chorioretinopathy and polypoidal choroidal vasculopathy. We describe an imaging technique using depth-resolved swept-source optical coherence tomography (SS-OCT) that provides full-thickness three-dimensional (3D) visualization of choroidal anatomy including topographical features of individual vessels. Enrolled subjects with different clinical manifestations within the pachychoroid disease spectrum underwent 15 mm × 9 mm volume scans centered on the fovea. A fully automated method segmented the choroidal vessels using their hyporeflective lumens. Binarized choroidal vessels were rendered in a 3D viewer as a vascular network within a choroidal slab. The network of choroidal vessels was color depth-encoded with a reference to the Bruch’s membrane segmentation. Topographical features of the choroidal vasculature were characterized and compared with choroidal imaging obtained with indocyanine green angiography (ICGA) from the same subject. The en face SS-OCT projections of the larger choroid vessels closely resembled to that obtained with ICGA, with the automated SS-OCT approach proving additional depth-encoded 3D information. In 16 eyes with pachychoroid disease, the SS-OCT approach added clinically relevant structural details, including choroidal thickness and vessel depth, which the ICGA studies could not provide. Our technique appears to advance the in vivo visualization of the full-thickness choroid, successfully reveals the topographical features of choroidal vasculature, and shows potential for further quantitative analysis when compared with other choroidal imaging techniques. This improved visualization of choroidal vasculature and its 3D structure should provide an insight into choroid-related disease mechanisms as well as their responses to treatment.     

Development of a 3D optical scanner for evaluating patient-specific dose distributions

PurposeThis paper describes the hardware and software characteristics of a 3D optical scanner (P3DS) developed in-house. The P3DS consists of an LED light source, diffuse screen, step motor, CCD camera, and scanner management software with 3D reconstructed software.Materials and methodWe performed optical simulation, 2D and 3D reconstruction image testing, and pre-clinical testing for the P3DS. We developed the optical scanner with three key characteristics in mind. First, we developed a continuous scanning method to expand possible clinical applications. Second, we manufactured a collimator to improve image quality by reducing scattering from the light source. Third, we developed an optical scanner with changeable camera positioning to enable acquisition of optimal images according to the size of the gel dosimeter.ResultsWe confirmed ray-tracing in P3DS with optic simulation and found that 2D projection and 3D reconstructed images were qualitatively similar to the phantom images. For pre-clinical tests, the dose distribution and profile showed good agreement among RTP, optical CT, and external beam radiotherapy film data for the axial and coronal views. The P3DS has shown that it can scan and reconstruct for evaluation of the gel dosimeter within 1 min. We confirmed that the P3DS system is a useful tool for the measurement of 3D dose distributions for 3D radiation therapy QA. Further experiments are needed to investigate quantitative analysis for 3D dose distribution.     

Optical coherence tomography as a noninvasive 3D real time imaging tool for the rapid evaluation of phenotypic variations in insect embryonic development

Noninvasive visualization of embryos at different development stages is crucial for the understanding of the basic developmental biology. It is therefore desirable to have an imaging tool capable of rapidly evaluating the effects of gene manipulation or genome editing in developing embryos for the studies of gene functions and genetic engineering. Here, we propose and demonstrate a novel use of optical coherence tomography (OCT) to noninvasively exam the embryonic development of the migratory locusts in real time with 3‐dimensional (3D) view capability. In particular, we obtain the sufficiently high spatial resolution tomographic 2D and 3D images of live locust embryos throughout their development processes. We show that not only we are able to noninvasively observe all previously known forms of blastokinesis as an embryo develops, such as anatrepsis, katatrepsis, revolution, rotation and diapauses, and determine their precise occurring time or duration, but also discover an unreported rotation form we named “twist.” In addition, with the OCT images we determined the exact occurring time of diapauses of the locusts from Tibetan plateau for the first time. Finally, we demonstrate that OCT systems can be used to rapidly capture the development defects of genetically modified embryos in which certain genes essential for embryonic development were suppressed by RNA interference. Our work shows that OCT is an enabling imaging tool with sufficient spatial resolution for the rapid evaluation of embryonic variations of small animals.     

Potential of contrast agents to enhance in vivo confocal microscopy and optical coherence tomography in dermatology: A review

Distinction between normal skin and pathology can be a diagnostic challenge. This systematic review summarizes how various contrast agents, either topically delivered or injected into the skin, affect distinction between skin disease and normal skin when imaged by optical coherence tomography (OCT) and confocal microscopy (CM). A systematic review of in vivo OCT and CM studies using exogenous contrast agents on healthy human skin or skin disease was performed. In total, nine CM studies and one OCT study were eligible. Four contrast agents aluminum chloride (AlCl) n = 2, indocyanine green (ICG) n = 3, sodium fluorescein n = 3 and acetic acid n = 1 applied to CM in variety of skin diseases. ICG, acetic acid and AlCl showed promise to increase contrast of tumor nests in keratinocyte carcinomas. Fluorescein and ICG enhanced contrast of keratinocytes and adnexal structures. In OCT of healthy skin gold nanoshells, increased contrast of natural skin openings. Contrast agents may improve delineation and diagnosis of skin cancers; ICG, acetic acid and AlCl have potential in CM and gold nanoshells facilitate visualization of adnexal skin structures in OCT. However, as utility of bedside optical imaging increases, further studies with robust methodological quality are necessary to implement contrast agents into routine dermatological practice.      

In vivo detection of tumor boundary using ultrahigh‐resolution optical coherence angiography and fluorescence imaging

Accurate detection of early tumor margin is of great preclinical and clinical implications for predicting the survival rate of subjects and assessing the response of tumor microenvironment to chemotherapy or radiation therapy. Here, we report a multimodality optical imaging study on in vivo detection of tumor boundary by analyzing neoangiogenesis of tumor microenvironment (microangiography), microcirculatory blood flow (optical Doppler tomography) and tumor proliferation (green fluorescent protein [GFP] fluorescence). Microangiography demonstrates superior sensitivity (77.7 ± 6.4%) and specificity (98.2 ± 1.7%) over other imaging technologies (eg, optical coherence tomography) for tumor margin detection. Additionally, we report longitudinal in vivo imaging of tumor progression and show that the abrupt tumor cell proliferation did not occur until local capillary density and cerebral blood flow reached their peak approximately 2 weeks after tumor implantation. The unique capability of longitudinal multimodality imaging of tumor angiogenesis may provide new insights in tumor biology and in vivo assessment of the treatment effects on anti‐angiogenesis therapy for brain cancer.     

Novel phantom for performance evaluation of contrast-enhanced 3D rotational angiography

PurposeThis technical note presents an in-house phantom with a specially designed contrast-object module constructed to address the need for three-dimensional rotational angiography (3DRA) testing.MethodsThe initial part of the study was a brief evaluation on the commercially available phantom used for 3DRA and computed tomography angiography (CTA) to confirm the need for a special phantom for 3D angiography. Once confirmed, an in-house phantom was constructed. The novel phantom was tested to evaluate the basic image performance metrics, i.e., unsharpness (MTF) and noise characterization (NPS), as well as to show its capability for vessel contrast visibility study.ResultsThe low contrast objects in the commercially available tools dedicated for CT is found to yield significantly lower signal difference to noise ratio (SDNR) when used for 3DRA, therefore deemed inadequate for 3DRA contrast evaluation. The constructed in-house phantom demonstrates a capability to serve for basic imaging performance check (MTF, NPS, and low contrast evaluation) for 3DRA and CTA. With higher and potentially adjustable visibility of contrast objects as artificial vessels, the in-house phantom also makes more clinically relevant tests, e.g., human- or model observer study and task-based optimization, possible.ConclusionThe novel phantom with special contrast object module shows higher visibility in 3DRA compared to the currently available commercial phantom and, therefore, is recommended for use in 3D angiography.     

三维几何形态学概述及其在昆虫学中的应用

长期以来二维（two-dimensional, 2D）数据是几何形态学（geometric morphometrics）分析的最主要的数据类型,在推动几何形态学的发展过程中起到了奠基性的作用,并也解决了很多重大的科学问题,展示了几何形态学强大的科学计算能力与问题解决能力。但有些特殊的科学问题或者特殊的形态结构,无法通过二维数据完美解决,亟需大规模、大尺度三维（three-dimensional, 3D）数据的支持,这对几何形态学的三维化发展提出需求。更重要的是,随着三维数据获取成本的日渐降低,大量三维数据涌现出来。因此,三维几何形态学应运而生。本文对三维几何形态学的原理及其应用进行了概述,重点探讨了三维几何形态学与二维几何形态学的异同点,并对前者的两个发展阶段（少量样本的形态模拟与准定量比较及大量样本的定量比较）进行了概述,评价了四维数据和有限元等方法的应用,指出了该方法在昆虫学领域的发展潜力,最后对该方法在样本量增加、硬件提升、数据分辨率提高、新算法的开发、分析结果的呈现及3D打印等方面的发展趋势进行了展望。     

基于Agisoft PhotoScan的石器三维建模与应用

打制石器是了解古人类认知、技术、行为等信息的重要物质载体之一,如何能够更加方便地观察绘制、测量以及展示石器是旧石器时代考古学中基础的研究内容。目前多视角影像三维重建技术在中国考古界应用越来越广泛,尤其是Agisoft PhotoScan软件的应用。相比其他类型遗物,石器的形制及片疤样式具有独特性,在建模过程难度较大。我们经过反复尝试,总结出了一套基于Agisoft PhotoScan软件,专门针对打制石器且易于掌握的建模方式,并从观察绘图、数字化、展示三个方面探讨了石器三维模型的应用。     

A new chemotype inhibitor for the human organic cation transporter 3 (hOCT3)

Human organic cation transporters (OCTs) represent an understudied neurotransmitter uptake mechanism for which no selective agents have yet been identified. Several neurotransmitters (e.g. serotonin, norepinephrine) are low-affinity substrates for these transporters, but possess higher affinity for other transporters (e.g. the serotonin or norepinephrine transporters; SERT and NET, respectively). We have identified a new class of OCT inhibitors with a phenylguanidine structural scaffold. Here, we examine the actions of a series of such compounds and report preliminary structure–activity relationships (SARs) – the first dedicated SAR study of OCT3 action. Initial results showed that the presence of a substituent on the phenyl ring, as well as its position, contributes to the phenylguanidines’ inhibitory potency (IC₅₀ values ranging from 2.2 to >450 μM) at hOCT3. There is a trend towards enhanced inhibitory potency of phenylguanidines with increased lipophilic character and the size of the substituent at the phenyl 4-position, with the latter reaching a ceiling effect. The first PiPT-based hOCT3 homology models were generated and are in agreement with our biological data.     

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.