光学相干层析用于牙齿病变的检测

阐述了适用于牙齿结构成像的光学相干层析成像(OCT)系统。系统光源中心波长为1 310 nm,成像分辨率10μm,在牙内成像深度2 mm,成像速度1幅/秒,系统信噪比100 dB。利用此OCT仪清晰检测到牙齿样品的牙釉质和牙本质,观察到牙釉质与牙本质的分界面以及正常牙齿牙釉质与龋齿牙齿牙釉质OCT图像的区别。进一步设计研制了适用于口腔内探测的小型OCT探头。     

Doppler Optical Coherence Tomography of Retinal Circulation

Noncontact retinal blood flow measurements are performed with a Fourier domain optical coherence tomography (OCT) system using a circumpapillary double circular scan (CDCS) that scans around the optic nerve head at 3.40 mm and 3.75 mm diameters. The double concentric circles are performed 6 times consecutively over 2 sec. The CDCS scan is saved with Doppler shift information from which flow can be calculated. The standard clinical protocol calls for 3 CDCS scans made with the OCT beam passing through the superonasal edge of the pupil and 3 CDCS scan through the inferonal pupil. This double-angle protocol ensures that acceptable Doppler angle is obtained on each retinal branch vessel in at least 1 scan. The CDCS scan data, a 3-dimensional volumetric OCT scan of the optic disc scan, and a color photograph of the optic disc are used together to obtain retinal blood flow measurement on an eye. We have developed a blood flow measurement software called "Doppler optical coherence tomography of retinal circulation" (DOCTORC). This semi-automated software is used to measure total retinal blood flow, vessel cross section area, and average blood velocity. The flow of each vessel is calculated from the Doppler shift in the vessel cross-sectional area and the Doppler angle between the vessel and the OCT beam. Total retinal blood flow measurement is summed from the veins around the optic disc. The results obtained at our Doppler OCT reading center showed good reproducibility between graders and methods (<10%). Total retinal blood flow could be useful in the management of glaucoma, other retinal diseases, and retinal diseases. In glaucoma patients, OCT retinal blood flow measurement was highly correlated with visual field loss (R²>0.57 with visual field pattern deviation). Doppler OCT is a new method to perform rapid, noncontact, and repeatable measurement of total retinal blood flow using widely available Fourier-domain OCT instrumentation. This new technology may improve the practicality of making these measurements in clinical studies and routine clinical practice.     

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。     

Decreased Cell Surface Charge in Cystic Fibrosis Epithelia

A colloid titration technique has been used to determine the surface charge of cystic fibrosis (CF) and corresponding non-CF epithelial cells. We have shown that the negative surface charge of CF epithelial cells is significantly reduced in comparison with non-CF cells. This fact may play an important role in CF, where the increased adherence of microorganisms is known to cause chronic lung infection. Neuraminidase treatment removed approximately the same amount of surface charge in both cell lines, indicating no differences in cell surface sialylation. Similar results were obtained by direct measurements of the amount of N-acetylneuraminic acid released by neuraminidase. Therefore, our results indicate that sialic acid residues are not involved in the reduction of the negative surface charge in CF. This conclusion does not support the hypothesis that undersialylation of cell-membrane molecules occurs in cystic fibrosis. © 1997 John Wiley & Sons, Ltd.     

Visualization of Plant Tissues by Optical Coherence Tomography

The internal structure of plant tissues was visualized with optical coherence tomography (OCT). This noninvasive method is suitable for examining intact plants; it produces two-dimensional images of plant tissues at a penetration depth of 1–2 mm from the surface. The potential use of OCT was assessed on Tradescantia blossfeldiana Mild. Plant tissue images measuring 1.5 × 2 mm were obtained in vivo with a spatial resolution of 15 m. The radiation power incident on a sample was 0.5 mW. The acquisition of a two-dimensional image consisting of 200 × 200 pixels required 1–3 s. The OCT method can be used to visualize not only plant tissues and tissue boundaries but also the structure of individual cells.     

Keratometric Index Obtained by Fourier-Domain Optical Coherence Tomography

Purpose

To determine the keratometric indices calculated based on parameters obtained by Fourier-domain optical coherence tomography (FD-OCT).

Methods

The ratio of anterior corneal curvature to posterior corneal curvature (Ratio) and keratometric index (N) were calculated within central 3 mm zone with the RTVue FD-OCT (RTVue, Optovue, Inc.) in 186 untreated eyes, 60 post-LASIK/PRK eyes, and 39 keratoconus eyes. The total corneal powers were calculated using different keratometric indices: K_cal based on the mean calculated keratometric index, K_1.3315 calculated by the keratometric index of 1.3315, and K_1.3375 calculated by the keratometric index of 1.3375. In addition, the total corneal powers based on Gaussian optics formula (K_actual) were calculated.

Results

The means for Ratio in untreated controls, post-LASIK/PRK group and keratoconus group were 1.176 ± 0.022 (95% confidence interval (CI), 1.172–1.179), 1.314 ± 0.042 (95%CI, 1.303–1.325) and 1.229 ± 0.118 (95%CI, 1.191–1.267), respectively. And the mean calculated keratometric index in untreated controls, post-LASIK/PRK group and keratoconus group were 1.3299 ± 0.00085 (95%CI, 1.3272–1.3308), 1.3242 ± 0.00171 (95%CI, 1.3238–1.3246) and 1.3277 ± 0.0046 (95%CI, 1.3263–1.3292), respectively. All the parameters were normally distributed. The differences between K_cal and K_actual, K_1.3315 and K_actual, and K_1.3375 and K_actual were 0.00 ± 0.11 D, 0.21 ± 0.11 D and 0.99 ± 0.12 D, respectively, in untreated controls; -0.01 ± 0.20 D, 0.85 ± 0.18 D and 1.56 ± 0.16 D, respectively, in post-LASIK/PRK group; and 0.03 ± 0.67 D, 0.56 ± 0.70 D and 1.40 ± 0.76 D, respectively, in keratoconus group.

Conclusion

The calculated keratometric index is negatively related to the ratio of anterior corneal curvature to posterior corneal curvature in untreated, post-LASIK/PRK, and keratoconus eyes, respectively. Using the calculated keratometric index may improve the prediction accuracies of total corneal powers in untreated controls, but not in post-LASIK/PRK and keratoconus eyes.     

Integrated Photoacoustic Ophthalmoscopy and Spectral-domain Optical Coherence Tomography

Both the clinical diagnosis and fundamental investigation of major ocular diseases greatly benefit from various non-invasive ophthalmic imaging technologies. Existing retinal imaging modalities, such as fundus photography¹, confocal scanning laser ophthalmoscopy (cSLO)², and optical coherence tomography (OCT)³, have significant contributions in monitoring disease onsets and progressions, and developing new therapeutic strategies. However, they predominantly rely on the back-reflected photons from the retina. As a consequence, the optical absorption properties of the retina, which are usually strongly associated with retinal pathophysiology status, are inaccessible by the traditional imaging technologies.Photoacoustic ophthalmoscopy (PAOM) is an emerging retinal imaging modality that permits the detection of the optical absorption contrasts in the eye with a high sensitivity^4-7 . In PAOM nanosecond laser pulses are delivered through the pupil and scanned across the posterior eye to induce photoacoustic (PA) signals, which are detected by an unfocused ultrasonic transducer attached to the eyelid. Because of the strong optical absorption of hemoglobin and melanin, PAOM is capable of non-invasively imaging the retinal and choroidal vasculatures, and the retinal pigment epithelium (RPE) melanin at high contrasts ^6,7. More importantly, based on the well-developed spectroscopic photoacoustic imaging^5,8 , PAOM has the potential to map the hemoglobin oxygen saturation in retinal vessels, which can be critical in studying the physiology and pathology of several blinding diseases ⁹ such as diabetic retinopathy and neovascular age-related macular degeneration.Moreover, being the only existing optical-absorption-based ophthalmic imaging modality, PAOM can be integrated with well-established clinical ophthalmic imaging techniques to achieve more comprehensive anatomic and functional evaluations of the eye based on multiple optical contrasts^6,10 . In this work, we integrate PAOM and spectral-domain OCT (SD-OCT) for simultaneously in vivo retinal imaging of rat, where both optical absorption and scattering properties of the retina are revealed. The system configuration, system alignment and imaging acquisition are presented.     

Correlations of Salivary Biomarkers with Clinical Assessments in Patients with Cystic Fibrosis

Rationale

Monitoring clinical disease status in cystic fibrosis frequently requires invasive collection of clinical samples. Due to its noninvasive collection process and direct anatomic relationship with the lower airway, saliva shows great potential as a biological fluid for cystic fibrosis monitoring.

Objectives

To measure the levels of multiple protein markers in human saliva supernatants and investigate the possibility of utilizing them to provide a more quantitative measure of disease state for use in research and monitoring of patients with cystic fibrosis clinically.

Methods

Whole saliva samples were collected and processed from cystic fibrosis patients at two distinct time points (2010 and 2013) and measured by two separate platforms. In this cross sectional study, a convenience sample of 71 participants were recruited with samples measured by multiplexed fluorescence microarray (fiber microarray) and another 117 participant samples were measured by an automated, point-of-care, analyzer (SDReader) using a microsphere-based array via fluorescence sandwich immunoassay. For comparison, saliva from 56 and 50 healthy subjects were collected, respectively. The levels of six target proteins were quantified. Various demographic and clinical data, including spirometry, medical history, and clinicians’ assessments were also collected from patients with cystic fibrosis on the day of saliva collection.

Measurements and Main Results

Similar trends were observed with both platforms and compared with healthy subjects, cystic fibrosis patients had significantly elevated levels of VEGF, IP-10, IL-8, and EGF as well as lower levels of MMP-9 (P ≤ 0.005) using fiber microarray and significantly elevated levels of IP-10, IL-8 with lower levels of MMP-9 and IL-1β (P ≤ 0.02) using the SDReader. The levels of the six proteins correlated with each other significantly, and in some cases, biomarker levels could be used to differentiate between subgroups of patients with different clinical presentations. For example, IP-10 levels significantly correlated with FEV₁ and disease severity (as evaluated by clinicians) with both platforms (P < 0.05).

Conclusions

Significant variations of the levels of six proteins in saliva supernatants, and the correlations of these levels with clinical assessments, demonstrated the potential of saliva for cystic fibrosis research and monitoring.     

光学相干层析分子成像方法初探

介绍了分子对比剂在光学相干层析成像(optical coherence tom ography,OCT)技术中的研究现状,概述了迄今出现的几种不同的光学相干层析分子成像方法(m olecu lar contrast OCT,简称为MCOCT),讨论了MCOCT的几个重要的实际问题:对比剂的选择范围、激发光强的限制、各种方法灵敏度比较以及MCOCT应用于临床与生物学领域需要考虑的因素。     

A Targeted Gain-of-Function Screen Identifies Genes Affecting Salivary Gland Morphogenesis/Tubulogenesis in Drosophila

During development individual cells in tissues undergo complex cell-shape changes to drive the morphogenetic movements required to form tissues. Cell shape is determined by the cytoskeleton and cell-shape changes critically depend on a tight spatial and temporal control of cytoskeletal behavior. We have used the formation of the salivary glands in the Drosophila embryo, a process of tubulogenesis, as an assay for identifying factors that impinge on cell shape and the cytoskeleton. To this end we have performed a gain-of-function screen in the salivary glands, using a collection of fly lines carrying EP-element insertions that allow the overexpression of downstream-located genes using the UAS-Gal4 system. We used a salivary-gland-specific fork head-Gal4 line to restrict expression to the salivary glands, in combination with reporters of cell shape and the cytoskeleton. We identified a number of genes known to affect salivary gland formation, confirming the effectiveness of the screen. In addition, we found many genes not implicated previously in this process, some having known functions in other tissues. We report the initial characterization of a subset of genes, including chickadee, rhomboid1, egalitarian, bitesize, and capricious, through comparison of gain- and loss-of-function phenotypes.     

基于光学相干层析术的斑马鱼颅骨密度定量分析方法

斑马鱼广泛地应用于骨退化相关的机制研究和新药开发过程中.目前临床应用检测骨密度(BMD)的方法主要有单光子吸收、双光子吸收、双能X线吸收、定量CT和超声技术等,上述方法均难用于斑马鱼的研究中.本文旨在寻求一种新式的、适用性强和操作简易的定量分析斑马鱼BMD的方法.对采集到的使用125μmol/L泼尼松龙溶液诱导骨质疏松...     

基于谱域相干的细胞动态检测技术

将谱域光学相干层析技术（Spectral-domain Optical Coherence Tomography,SD-OCT）应用于细胞膜厚的动态检测,引入了光谱干涉测量方法,通过对干涉光谱信号进行离散傅里叶变换得到表示物体深度位置信息的光程差信号。搭建了一套SD-OCT测量系统并设计了专门用于细胞检测的样品平台,检测精度达到μm量级,信噪比达70 db,是一种快速、实时、非接触的细胞分子膜厚动态检测技术。     

Optical Coherence Tomography and Autofluorescence Imaging of Human Tonsil

For the first time, we present co-registered autofluorescence imaging and optical coherence tomography (AF/OCT) of excised human palatine tonsils to evaluate the capabilities of OCT to visualize tonsil tissue components. Despite limited penetration depth, OCT can provide detailed structural information about tonsil tissue with much higher resolution than that of computed tomography, magnetic resonance imaging, and Ultrasound. Different tonsil tissue components such as epithelium, dense connective tissue, lymphoid nodules, and crypts can be visualized by OCT. The co-registered AF imaging can provide matching biochemical information. AF/OCT scans may provide a non-invasive tool for detecting tonsillar cancers and for studying the natural history of their development.     

Optical Coherence Tomography for live imaging of mammalian development

Understanding the nature and mechanism of congenital defects of the different organ systems in humans has heavily relied on the analysis of the corresponding mutant phenotypes in rodent models. Optical Coherence Tomography (OCT) has recently emerged as a powerful tool to study early embryonic development. This non-invasive optical methodology does not require labeling and allows visualization of embryonic tissues with single cell resolution. Here, we will discuss how OCT can be applied for structural imaging of early mouse and rat embryos in static culture, cardiodynamic and blood flow analysis, and in utero embryonic imaging at later stages of gestation, demonstrating how OCT can be used to assess structural and functional birth defects in mammalian models.     

Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease

Background and Aims

Cystic Fibrosis associated liver disease (CFLD) develops in approximately 30% of CF patients. However, routine sensitive diagnostic tools for CFLD are lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CFLD.

Methods

45 CF patients were included in the study and received transient elastography. Differential regulation of 220 different serum proteins was assessed in a subgroup of patients with and without CFLD. Most interesting candidate proteins were further quantified and validated by ELISA in the whole patient cohort. To assess a potential relation of biomarker expression to the degree of hepatic fibrosis, serum biomarkers were further determined in 18 HCV patients where liver histology was available.

Results

43 serum proteins differed at least 2-fold in patients with CFLD compared to those without liver disease as identified in proteome profiling. In ELISA quantifications, TIMP-4 and Endoglin were significantly up-regulated in patients with CFLD as diagnosed by clinical guidelines or increased liver stiffness. Pentraxin-3 was significantly decreased in patients with CFLD. Serum TIMP-4 and Endoglin showed highest values in HCV patients with liver cirrhosis compared to those with fibrosis but without cirrhosis. At a cut-off value of 6.3 kPa, transient elastography compassed a very high diagnostic accuracy and specificity for the detection of CFLD. Among the biomarkers, TIMP-4 and Endoglin exhibited a high diagnostic accuracy for CFLD. Diagnostic sensitivities and negative predictive values were increased when elastography and TIMP-4 and Endoglin were combined for the detection of CFLD.

Conclusions

Serum TIMP-4 and Endoglin are increased in CFLD and their expression correlates with hepatic staging. Determination of TIMP-4 and Endoglin together with transient elastography can increase the sensitivity for the non-invasive diagnosis of CFLD.     

Tissue-Specific Optical Mapping Models of Swine Atria Informed by Optical Coherence Tomography

Computational models and experimental optical mapping of cardiac electrophysiology serve as powerful tools to investigate the underlying mechanisms of arrhythmias. Modeling can also aid the interpretation of optical mapping signals, which may have different characteristics with respect to the underlying electrophysiological signals they represent. However, despite the prevalence of atrial arrhythmias such as atrial fibrillation, models of optical electrical mapping incorporating realistic structure of the atria are lacking. Therefore, we developed image-based models of atrial tissue using structural information extracted from optical coherence tomography (OCT), which can provide volumetric tissue characteristics in high resolution. OCT volumetric data of four swine atrial tissue samples were used to develop models incorporating tissue geometry, tissue-specific myofiber orientation, and ablation lesion regions. We demonstrated the use of these models through electrophysiology and photon scattering simulations. Changes in transmural electrical conduction were observed with the inclusion of OCT-derived, depth-resolved fiber orientation. Additionally, the amplitude of optical mapping signals were not found to correspond with lesion transmurality because of lesion geometry and electrical propagation occurring beyond excitation light penetration. This work established a framework for the development of tissue-specific models of atrial tissue derived from OCT imaging data, which can be useful in future investigations of electrophysiology and optical mapping signals with respect to realistic atrial tissue structure.     

Severe Ectopic Cushing Syndrome Caused by Adenoid Cystic Carcinoma of a Salivary Gland

ObjectiveWe present a rare case of Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS). To our knowledge only two similar cases have been previously reported.MethodsThis is a case report of EAS by a metastatic lingual adenoid cystic carcinoma (ACC).ResultsThe patient was diagnosed of a Cushing syndrome caused by tumoral EAS two years after initial cancer diagnosis. Clinical presentation included asthenia, insomnia, hypertension, acne, and hyperpigmentation developing in a period of two months. Laboratory and imaging testing revealed hypokalemic metabolic alkalosis, hypercortisole- mia, high ACTH, nonsuppresion by 8 mg dexamethasone, and a normal pituitary magnetic resonance imaging (MRI). With a high clinical suspicion of EAS, combined medical treatment was started but was unsuccessful. Bilateral adrenalectomy could not be performed given the patient’s rapid deterioration. Immunostained tissue from the original tumor was positive for synaptophysin.ConclusionThis rare case of EAS illustrates the challenge that this condition may confer regarding diagnosis and management. (Endocr. Pract. 2013;19:e118-e121)     

基于光学相干层析成像技术的小鼠表皮厚度的无损测量及分析

光学相干层析成像技术(optical coherence tomography,OCT)在研究活体皮肤的表皮和真皮上层方面是一种很有潜力的手段.本文以小白鼠为研究对象,脱毛后,采用OCT系统对同一部位的小鼠皮肤在制作切片过程中(活体、离体、固定24 h后)进行成像跟踪,分别获得OCT强度图中第一强度峰到第一个波谷,以及第一、二强度峰之间的距离,比较两种结果和组织学的对应情况,并分析其原因,同时关注切片过程中各种物理、化学因素对皮肤各层厚度的影响,研究了OCT图像的各个反射峰与实际皮肤的结构之间联系.     

Pulmonary Emphysema in Cystic Fibrosis Detected by Densitometry on Chest Multidetector Computed Tomography

Background

Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF.

Methods

Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC).

Results

We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (r_s=-0.66), and directly with RV (r_s=0.69) and RV/TLC (r_s=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (r_s=0.67, P<0.001).

Conclusions

Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF.     

Growth Kinetics of Concave Nanocubes Studied by Optical Coherence Tomography

This work presents the analysis of the growth kinetics of two syntheses of concave gold nanocubes with a mean size of 72 and 108 nm followed by the optical coherence tomography (OCT) technique by acquiring B-scan images each 5 s. In addition, ultra violet-visible (UV-Vis) spectra and mean size from dynamic light scattering (DLS) were acquired during nanoparticle growth to generate kinetic plots in order to corroborate the OCT results. Kinetic plots from OCT images were obtained by plotting contrast enhancement of B-scan images as function of time. Fitting parameters values given by using the classical Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation show that the growth rate parameter k is higher for small cubes than for large ones, and that the Avrami exponent n associated to the growth kinetics of concave nanocubes is close to 2 for both syntheses. The results of UV-Vis spectroscopy and DLS confirm that OCT is a viable technique to provide information about nanoparticle growth kinetics. Moreover, to our knowledge, this is the first time that OCT technique is used to follow nanoparticle growth kinetics.