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Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics最新文献

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Front Matter: Volume 10885 封面:卷10885
Pub Date : 2019-05-22 DOI: 10.1117/12.2523431
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引用次数: 2
Quantificiation of hemoglobin concentrations in whole blood by visible-light spectroscopic optical coherence tomography (Conference Presentation) 用可见光光谱光学相干断层扫描定量测定全血血红蛋白浓度(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2509866
C. Veenstra, S. Kruitwagen, Dafne Groener, Wilma Petersen, W. Steenbergen, Nienke Bosschaart
A decreased hemoglobin concentration (tHb) in blood (anemia) is associated with impaired oxygen delivery to organs, which can result in organ damage and heart failure. Currently, tHb analysis requires invasive methods (e.g. a fingerstick), which are time consuming and cause discomfort to the patient. Using optical spectroscopy, the tHb can be estimated by quantifying light absorption in blood. However, the accuracy of current noninvasive optical techniques for tHb quantification is limited by the background attenuation of skin and the unknown blood volume fraction in the total optical probing volume.Spectroscopic optical coherence tomography (sOCT) allows for quantitative measurements of the optical attenuation in a confined measurement volume, potentially enabling non-invasive estimation of the hemoglobin concentration within individual blood vessels. Although multiple studies have shown that sOCT is capable of quantifying localized oxygen saturation, quantification of the tHb has not yet been reported for physiologically relevant concentrations.With a home-built visible-light sOCT system we quantified optical attenuation in the visible wavelength range (450–600nm). Implementation of both zero-delay acquisition and focus tracking optimized system sensitivity and ensured that the measured attenuation is only affected by the attenuation of the sample itself. We validated our method ex-vivo on human whole blood from healthy volunteers (tHb within 12-18 g/dL). The hematocrit was varied to cover the entire pathophysiological range (tHb within 9-21 g/dL) by either dilution with PBS, or plasma removal. Our system quantified the tHb in whole blood throughout the entire pathophysiological range with an accuracy of 10%.
血液中血红蛋白浓度(tHb)的降低(贫血)与器官供氧受损有关,这可能导致器官损伤和心力衰竭。目前,tHb分析需要侵入性方法(例如手指戳),这既耗时又会给患者带来不适。利用光谱学,可以通过量化血液中的光吸收来估计tHb。然而,目前用于tHb定量的非侵入性光学技术的准确性受到皮肤背景衰减和总光学探测体积中未知的血容量分数的限制。光谱光学相干断层扫描(sOCT)允许在有限的测量体积内对光学衰减进行定量测量,有可能实现对单个血管内血红蛋白浓度的非侵入性估计。尽管多项研究表明,sOCT能够定量局部氧饱和度,但尚未有关于生理相关浓度的tHb定量的报道。利用自制的可见光sOCT系统,我们量化了可见光波长范围(450-600nm)的光衰减。零延迟采集和焦点跟踪的实现优化了系统灵敏度,并确保测量的衰减仅受样品本身衰减的影响。我们在健康志愿者的人全血(tHb在12-18 g/dL)上验证了我们的方法。通过PBS稀释或血浆去除,红细胞压积变化到覆盖整个病理生理范围(tHb在9-21 g/dL)。我们的系统在整个病理生理范围内定量全血中tHb,准确度为10%。
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引用次数: 0
Monitoring therapeutic response of murine tumor allografts of colon carcinoma in response to combined immunotherapy and chemotherapy (Conference Presentation) 小鼠结肠癌同种异体肿瘤移植对免疫化疗联合治疗反应的监测(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2510194
G. Greening, S. Bess, Haley M. James, Ariel I. Mundo, Timothy J. Muldoon
Immunotherapy, an emerging field in cancer therapeutics, in colon cancer aims to reduce pre-surgical tumor burden by regulating host immune checkpoints, and when used in combination with neoadjuvant chemotherapy, may improve tumor therapeutic response. One such immune checkpoint is CCL2 (monocyte chemoattractant protein-1)-mediated recruitment of monocytes, which differentiate into tumor-associated macrophages (TAMs) in the tumor microenvironment that promote angiogenesis and tumorigenesis. Thus, CCL2 blockade may play an anti-tumor role via effects on tumor perfusion. However, there have been no studies investigating CCL2 blockade immunotherapy combined with chemotherapy in an animal model of colon cancer. Furthermore, there is a need to longitudinally assess tumor therapeutic response throughout treatment. In this study, CT26 murine colon carcinoma was injected into the flanks of Balb/c mice (n=80) to form tumor allografts. Mice in the key experimental group received combined chemotherapy (5-flurouracil) and immunotherapy (anti-CCL2), with appropriate controls. Tumor therapeutic response was monitored using diffuse reflectance spectroscopy (DRS) by measuring the tumor perfusion metrics, hemoglobin concentration and oxygenation. End-point immunohistochemical analysis was used to quantify TAM fraction (CD68 and DAPI), TAM polarization (iNOS and CD206), and hypoxia (pimonidazole) to spatially and temporally correlate to DRS results. The central hypothesis was that decreasing TAMs via CCL2 blockade alters tumor perfusion, thereby increasing tumor response to 5-fluorouracil. This study may potentially demonstrate an effective immunotherapy approach (CCL2 blockade) and a viable method to longitudinally and non-invasively assess tumor therapeutic response to such immunotherapy (DRS) in mouse allograft models of colon cancer.
免疫治疗是癌症治疗中的一个新兴领域,其目的是通过调节宿主免疫检查点来减轻结肠癌的术前肿瘤负担,当与新辅助化疗联合使用时,可能会改善肿瘤的治疗反应。其中一个免疫检查点是CCL2(单核细胞趋化蛋白-1)介导的单核细胞募集,单核细胞在肿瘤微环境中分化为肿瘤相关巨噬细胞(tam),促进血管生成和肿瘤发生。因此,CCL2阻断可能通过影响肿瘤灌注发挥抗肿瘤作用。然而,目前还没有关于CCL2阻断免疫疗法联合化疗在结肠癌动物模型中的研究。此外,有必要在整个治疗过程中对肿瘤治疗反应进行纵向评估。本研究将CT26小鼠结肠癌注射到Balb/c小鼠(n=80)的侧翼形成肿瘤同种异体移植物。重点实验组小鼠给予5-氟尿嘧啶联合化疗和抗ccl2免疫治疗,并辅以适当对照。通过漫反射光谱(DRS)测量肿瘤灌注指标、血红蛋白浓度和氧合来监测肿瘤治疗反应。终点免疫组织化学分析用于量化TAM分数(CD68和DAPI), TAM极化(iNOS和CD206)和缺氧(吡莫硝唑),以确定其与DRS结果的时空相关性。中心假设是通过CCL2阻断降低tam改变肿瘤灌注,从而增加肿瘤对5-氟尿嘧啶的反应。这项研究可能潜在地证明了一种有效的免疫治疗方法(CCL2阻断)和一种可行的方法来纵向和无创地评估结肠癌小鼠同种异体移植模型对这种免疫治疗(DRS)的肿瘤治疗反应。
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引用次数: 0
Tissue auto-fluorescence lifetime imaging in porcine burn wound models (Conference Presentation) 组织自荧光寿命成像在猪烧伤模型中的应用(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2510590
Suhaib Hashem, J. Lo
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引用次数: 0
Objective determination of heart failure grade using short wave infrared (SWIR) molecular chemical imaging (Conference Presentation) 利用短波红外(SWIR)分子化学成像客观确定心力衰竭分级(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2509802
Aaron Smith, Shona Stewart, A. Samiei, A. Bangalore, Heather Gomer, C. Post, P. Treado, Jeffrey A. Cohen
Heart failure (HF) occurs when the heart is unable to pump enough blood to meet blood and oxygen requirements and is among the most common causes for hospitalization in the United States. A retrospective analysis determined that 22% of HF patients are readmitted within 30 days of release from the hospital, and the costs for readmission are substantial. Measuring the severity of peripheral edema is one method for monitoring the treatment of a HF patient. Pitting peripheral edema is a subjective measure administered by clinicians who create an indentation mid-tibia and observe depth and time to resolve the indentation. The results are graded 0, 1, 2, 3 or 4, and this information is used in the patient treatment plan. ChemImage is engaged in a clinical study to determine whether Molecular Chemical Imaging (MCI) in the short wave infrared (SWIR) spectral region can provide an objective measure of peripheral edema in HF patients. In this paper, the performance of SWIR MCI for discriminating between healthy volunteers and HF patients with high grade pitting edema will be presented. This technology may provide a non-invasive methodology for quantitative peripheral edema measurement. As the technology matures, it is envisioned patient self-monitoring, with wireless transmission of edema levels while at home, can aid clinicians in monitoring HF patients for necessary treatment changes remotely, to improve patient outcomes, and ultimately, reduce HF hospital readmission rates.
心力衰竭(HF)发生时,心脏不能泵出足够的血液,以满足血液和氧气的需求,是最常见的原因住院在美国。一项回顾性分析表明,22%的心衰患者在出院后30天内再次入院,再次入院的费用很高。测量周围水肿的严重程度是监测心衰患者治疗的一种方法。点状外周水肿是一种主观测量方法,由临床医生在胫骨中部形成压痕,观察压痕愈合的深度和时间。结果分为0、1、2、3或4级,这些信息用于患者的治疗计划。ChemImage正在进行一项临床研究,以确定短波红外(SWIR)光谱区域的分子化学成像(MCI)是否可以客观地衡量HF患者的外周水肿。本文将介绍SWIR MCI在区分健康志愿者和高级别点蚀性水肿的心衰患者中的表现。这项技术可以提供一种非侵入性的外周水肿定量测量方法。随着技术的成熟,设想患者自我监测,在家中通过无线传输水肿水平,可以帮助临床医生远程监测心衰患者必要的治疗变化,以改善患者的预后,并最终降低心衰住院再入院率。
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引用次数: 1
Coke or Diet Coke? (Conference Presentation) 可乐还是健怡可乐?(会议)
Pub Date : 2019-03-13 DOI: 10.1117/12.2510939
V. Yakovlev
Raman spectroscopy is a powerful tool in biomedical imaging and sensing; however, despite all its undisputed advantages, its intrinsic sensitivity is relatively low, and its specificity is rather limited due to overlapping vibrational bands. Fluorescence background often masks the useful signal, and dark rooms are normally required to avoid an unnecessary background.In this report, we will present our recent efforts on improving reliability and simplicity of deep UV Raman spectroscopy, which provides much improved sensitivity and specificity of detection (for example, we can routinely distinguish Coke® from Diet Coke® in a matter of milliseconds).
拉曼光谱是生物医学成像和传感的有力工具;然而,尽管它具有所有无可争议的优点,但其固有灵敏度相对较低,并且由于振动带重叠,其特异性相当有限。荧光背景往往掩盖了有用的信号,暗室通常需要避免不必要的背景。在本报告中,我们将介绍我们最近在提高深紫外拉曼光谱的可靠性和简单性方面所做的努力,这大大提高了检测的灵敏度和特异性(例如,我们通常可以在几毫秒内区分可乐®和健怡可乐®)。
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引用次数: 0
Non-contact biophotonic assessment of changes in central venous pressure using photoplethysmographic imaging (Conference Presentation) 非接触生物光子评估中心静脉压的变化使用光容积脉搏图成像(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2510763
R. Amelard, J. Au, K. Murray, D. Greaves, R. Hughson
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引用次数: 0
Changes of mean arterial pressure affect spinal cord oxygenation as monitored by an implantable near-infrared spectroscopy sensor in an animal model of acute spinal cord injury (Conference Presentation) 急性脊髓损伤动物模型植入式近红外光谱传感器监测平均动脉压变化对脊髓氧合的影响(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2506715
B. Shadgan, Allan Fong, N. Manouchehri, K. So, Katelyn Shortt, F. Streijger, A. Macnab, B. Kwon
Introduction: Current clinical practice guidelines for acute spinal cord injury (SCI) patients suggest that increasing the mean arterial pressure (MAP) to 85-90 mmHg may improve spinal cord (SC) hemodynamics and oxygenation. The purpose of this study was to examine this effect using an implantable Near Infra-Red Spectroscopy (NIRS) sensor. Methods: Nine anesthetized Yorkshire pigs were studied. A multi-wavelength NIRS system with a custom-made miniaturized optical sensor was applied directly onto the SC dura at T9 to measure tissue oxygenation and hemodynamics within the SC non-invasively. To validate the NIRS measures, an invasive Intraparenchymal (IP) combined O2/blood flow sensor was inserted directly into the SC adjacent to the NIRS probe at T11. Using NIRS, the SC tissue oxygenation percentage (TOI%), as well as concentrations of oxygenated, deoxygenated and total hemoglobin, were monitored before, during and after episodes of MAP alterations. Using norepinephrine and nitroprusside, MAP was increased and decreased by 20mmHg for 30 min periods, simulating the types of hemodynamic changes that SCI patients experience post-injury. Results: Changes in SC hemodynamics and oxygenation levels were detected in all subjects as measured by both the invasive IP and the non-invasive NIRS sensors. Changes of TOI% during MAP increase (1.64%, p<0.005) and decrease (-3.97%, p<0.005) were significant. A consistent decrease in TOI (-15.94%, p<0.005) was observed following SCI, indicating SC tissue hypoxia at the injury site. Conclusions: Using a miniaturized SC NIRS sensor we have shown the significant effect of MAP alterations on tissue oxygenation within the injured SC.
目前急性脊髓损伤(SCI)患者的临床实践指南表明,将平均动脉压(MAP)提高到85-90 mmHg可能会改善脊髓(SC)的血流动力学和氧合。本研究的目的是使用植入式近红外光谱(NIRS)传感器来检查这种影响。方法:对9头麻醉的约克郡猪进行研究。在T9时,将多波长NIRS系统与定制的微型光学传感器直接应用于SC硬脑膜上,以无创地测量SC内的组织氧合和血流动力学。为了验证NIRS测量,在T11处将有创性肺实质内(IP)联合O2/血流传感器直接插入靠近NIRS探头的SC。使用近红外光谱(NIRS),在MAP改变发作之前、期间和之后监测SC组织氧合百分比(TOI%),以及氧合、脱氧和总血红蛋白的浓度。使用去甲肾上腺素和硝普赛,MAP在30分钟的时间内增加和减少20mmHg,模拟SCI患者损伤后血流动力学的变化类型。结果:通过侵入性IP和非侵入性NIRS传感器测量,所有受试者均检测到SC血流动力学和氧合水平的变化。MAP升高(1.64%,p<0.005)和降低(-3.97%,p<0.005)期间TOI%的变化具有显著性。脊髓损伤后TOI持续下降(-15.94%,p<0.005),表明损伤部位SC组织缺氧。结论:使用小型SC近红外传感器,我们已经显示了MAP改变对损伤SC内组织氧合的显著影响。
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引用次数: 0
Optical waveguides for on-chip fluorescence measurements (Conference Presentation) 片上荧光测量用光波导(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2508228
P. Lin, G. Coté, Kristen C. Maitland, Tiening Jin, Junchao Zhou, Paul Gordon, Cyril Soliman
Optical waveguides using a visible transparent nitride were developed to perform fluorescence measurement on a chip. Through finite difference time domain (FDTD) design, the exciting green light was guided by the micron-scale ridge waveguide, while its evanescent wave was expanded outside the waveguide surface and capable to efficiently excite the fluorescent molecules that were approaching the waveguide facets. Since the waveguide was centimeters long, it has a longer fluorescence excitation path comparing to traditional samples prepared for microscopy measurements. As result, the waveguide device can excite stronger fluorescent signals. In addition, the nitride waveguide was prepared by the complementary metal–oxide–semiconductor (CMOS) process thus enabling high volume manufacturing and reducing the cost of the device fabrication. The AlN waveguide was then integrated with a microfluidic devices to experimentally demonstrate real-time fluorescence detection. Solution samples with different dye concentrations were sequentially injected into the microfluidic chamber. By recording the emission signals, we showed that the fluorescent signals were consistently amplified as the dye concentrations increased. In addition, real-time fluorescence detection with a response time less than seconds was achieved. The developed waveguide based fluorescence measurement provides a new miniaturized platform for low cost and highly accurate point-of-care application.
利用可见透明氮化物的光波导在芯片上进行荧光测量。通过时域有限差分(FDTD)设计,激发的绿光由微米尺度脊波导引导,其倏逝波扩展到波导表面外,能够有效地激发接近波导表面的荧光分子。由于波导有几厘米长,与用于显微镜测量的传统样品相比,它具有更长的荧光激发路径。因此,波导装置可以激发更强的荧光信号。此外,氮化物波导是通过互补金属氧化物半导体(CMOS)工艺制备的,从而实现了大批量生产并降低了器件制造成本。然后将AlN波导与微流控器件集成,实验证明了实时荧光检测。将不同染料浓度的溶液样品依次注入微流控室。通过记录发射信号,我们发现荧光信号随着染料浓度的增加而不断放大。此外,还实现了响应时间小于秒的实时荧光检测。所开发的基于波导的荧光测量为低成本和高精度的护理点应用提供了一个新的小型化平台。
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引用次数: 0
Leukocyte dynamics in cutaneous acute graft-versus-host disease by noninvasive laser confocal video microscopy: a cross-sectional pilot study (Conference Presentation) 非侵入性激光共聚焦视频显微镜下皮肤急性移植物抗宿主病的白细胞动力学:一项横断面试点研究(会议报告)
Pub Date : 2019-03-13 DOI: 10.1117/12.2510585
I. Saknite, M. Byrne, M. Jagasia, E. Tkaczyk
Inflammatory tissue response is one of the first and most common manifestations of acute graft-versus-host disease (aGVHD), a potentially deadly immune-mediated disease that occurs in 30-60% of patients after stem cell transplantation. A fundamental challenge in developing effective treatment strategies for aGVHD is the lack of tools to study disease biology in real-time in post-transplant patients. The inflammatory tissue response causes increased expression of specialized endothelial proteins on vessel walls making leukocytes to roll, adhere and eventually extravasate into the tissue at a higher rate than in normal conditions. Although the importance of leukocyte-endothelial interactions to detect and track inflammation has been well shown in murine models, there are no published clinical studies in humans. In this study, we explore the feasibility to detect presence of aGVHD in post-transplant patients through the imaging of in vivo leukocyte motion. We used a clinical confocal microscope (Vivascope 1500) to acquire videos of 5 aGVHD patients and 5 controls (no aGVHD) within 50±30 days post-transplant. The microscope is capable of real-time imaging of individual cells in the postcapillary vessels at 9 frames per second. Through video analysis, we extracted five quantitative parameters: number and velocity of rolling leukocytes, number of adherent leukocytes (stationary >30 s), blood flow velocity, and number of vessels. In a limited number of subjects, we show that parameters characteristic of the dynamic motion in skin capillaries can be observed noninvasively in post-transplant patients. Further studies are needed to test the diagnostic potential of these parameters.
炎症组织反应是急性移植物抗宿主病(aGVHD)的首要和最常见的表现之一,aGVHD是一种潜在致命的免疫介导疾病,发生在30-60%的干细胞移植后患者中。开发aGVHD有效治疗策略的一个基本挑战是缺乏实时研究移植后患者疾病生物学的工具。炎症组织反应导致血管壁上特异性内皮蛋白的表达增加,使白细胞滚动、粘附并最终以比正常情况下更高的速率外渗到组织中。尽管白细胞内皮相互作用对检测和跟踪炎症的重要性已经在小鼠模型中得到了很好的证明,但在人类身上还没有发表的临床研究。在本研究中,我们探讨了通过体内白细胞运动成像检测移植后患者aGVHD存在的可行性。我们使用临床共聚焦显微镜(Vivascope 1500)获取移植后50±30天内5例aGVHD患者和5例对照组(无aGVHD)的视频。该显微镜能够以每秒9帧的速度实时成像毛细血管后的单个细胞。通过视频分析,我们提取了5个定量参数:滚动白细胞数量和速度、粘附白细胞数量(静止>30 s)、血流速度、血管数量。在有限数量的受试者中,我们表明可以在移植后患者中无创地观察到皮肤毛细血管动态运动的参数特征。需要进一步的研究来测试这些参数的诊断潜力。
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引用次数: 0
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Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
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