Quantitative Biophotonics for Tissue Characterization and Function

用于组织表征和功能的定量生物光子学

• 批准号: 10688910
• 负责人: Amir H Gandjbakhche
• 金额: $ 73.88万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688910
• 关键词: Abdomen; Acute; Adipose tissue; Algorithms; Anatomy; Anemia; Apple watch; Arteries; Asphyxia; Asphyxia Neonatorum; Biological Phenomena; Biophotonics; Biosensor; Birth; Blood; Blood Vessels; Blood capillaries; Blood flow; Blurred vision; Body Temperature; Body part; Brain; Breathing; COVID-19; COVID-19 outbreak; COVID-19 patient; Cardiac; Cell Death; Cells; Cellular Metabolic Process; Cerebral Palsy; Cervix Uteri; Cessation of life; Child; Chronic; Clinical; Clinical Protocols; Clinical Trials; Collaborations; Communicable Diseases; Computer Simulation; Contralateral; Country; Data; Decidua Basalis; Devices; Diagnostic Procedure; Diagnostic tests; Diffuse; Disease Outbreaks; Early Intervention; Elements; Environment; Esomeprazole; Evaluation; Fetal Death; Fetal Growth Retardation; Fetal Monitoring; Fetal Movement; Fetus; Frequencies; Future; Gaussian model; Genetic; Growth; Headache; Health; Health Professional; Healthcare Systems; Hela Cells; Hemoglobin; Hypercapnia; Hypertension; Hypoxia; Image; Image Analysis; Impaired cognition; Injury; Intervention; Japan; Kaposi Sarcoma; Kidney Failure; Knowledge; Label; Lasers; Lead; Lesion; Lipids; Liver Failure; Location; Logistic Regressions; Malignant - descriptor; Malignant Neoplasms; Malnutrition; Measurement; Measures; Medical center; Metabolic; Metabolism; Metformin; Methodology; Methods; Michigan; Modeling; Monitor; Morbidity - disease rate; Mothers; Motion; Muscle; Near-Infrared Spectroscopy; Normal tissue morphology; Optical Coherence Tomography; Optical Methods; Optics; Organ; Organ failure; Outcome; Oxygen; Participant; Pathology; Patient observation; Patients; Pattern; Performance; Perfusion; Perinatal mortality demographics; Perinatology; Personal Satisfaction; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Physiological; Pituitary-dependent Cushing' s disease; Placenta; Polyhydramnios; Population; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Premature Birth; Prenatal care; Property; Proteins; Protocols documentation; Pulse Oximetry; Research; Research Personnel; Respiratory physiology; Rest; Risk; Sample Size; Scientist; Signal Transduction; Site; Skin; Source; Spectrum Analysis; Stress; Symptoms; System; Techniques; Technology; Temperature Sense; Testing; Thermography; Third Pregnancy Trimester; Time; Tissue imaging; Tissues; Transillumination; Traumeel S; Treatment Protocols; Treatment outcome; United States National Institutes of Health; Urine; Uterus; Variant; Veins; Virus; Virus Diseases; Visit; Walking; Water; Weight; Work; absorption; algorithm development; arm; chromophore; comparative; coronavirus disease; density; design; detector; early pregnancy; experimental study; fetal; fetus nutrition; fitbit; gene therapy; healthy pregnancy; healthy volunteer; human subject; in utero; in vivo; indexing; infancy; instrumentation; machine learning model; monitoring device; motion sensor; multimodality; novel; novel coronavirus; novel diagnostics; obstetric care; photonics; random forest; respiratory; response; sensor; sildenafil; spectrograph; spectroscopic imaging; supervised learning; support vector machine; theories; tissue oxygenation; tomography; tool; volunteer; wearable device; wearable sensor technology

Observing the placenta offers a look into the in utero fetal environment. Variations in the size of the placenta throughout early pregnancy have been associated with placental injury from factors such as maternal malnutrition or anemia. Reduced uteroplacental perfusion is often associated with fetal growth restriction (FGR), a condition where the fetus fails to reach their genetic growth potential, and the associated condition, pre-eclampsia. In cases of pre-eclampsia, pregnant women will often have hypertension, protein in their urine, and symptoms such as blurred vision and headaches, posing significant health risks to the mother. Additionally, pre-eclampsia and fetal growth restriction can increase risk for perinatal death of the fetus and premature delivery. Reduced uteroplacental perfusion can also lead to chronic hypoxia, a condition where the tissue is not oxygenated adequately, and poor fetal nutrition. These factors increase risk for cognitive impairments in the child, including cerebral palsy and lifelong metabolic outcomes. Additionally, reduced perfusion can lead to perinatal asphyxia, a lack of oxygen and blood flow to the fetus before, during, or immediately after birth. More severe cases of asphyxia, where the fetus has low oxygen levels for an extended period, may result in permanent damage to the babys major organs, including the brain, liver, and kidneys, or organ failure and death. Therefore, monitoring placental oxygenation may be useful in distinguishing between a normal fetus and one with FGR and/or associated conditions and might predict pregnancy outcome. Additionally, identification of such complications during pregnancy can allow for earlier interventions, including medications to reduce risk of perinatal mortality (e.g., sildenafil, esomeprazole, and metformin) and maternal gene therapy. While research on these interventions is still in its infancy, identifying pregnancy complications prior to birth may allow mothers and their physicians to take necessary precautions. Near-infrared spectroscopy (NIRS) is an optical method for the non-invasive measurement of blood oxygenated and deoxygenated hemoglobin and tissue oxygenation in deep tissue layers such as the brain, muscle, and placenta. A major challenge in the assessment of placental oxygenation using NIRS arises from the anatomical location of the organ. Taking into account the anatomical location of the maternal placenta (e.g. skin, adipose tissue, uterine wall), a novel wearable depth-resolved NIRS device featuring six source-detector distances ranging from 10-60 mm has been designed to scope different tissue layers. The performance evaluation of the NIRS device was confirmed and validated in two human subjects at multiple parts of the body including both arms, calves, and abdomen with a commercial time-domain NIRS system (TRS-41 system, Hamamatsu photonics, Japan). An averaged error of 2.7% was found between the two device/system. The NIRS device was then used to measure in-vivo placental oxygenation in 12 volunteer subjects at the Center for Advanced Obstetrical Care and Research of the Perinatology Research Branch, located at the Detroit Medical Center (DMC, Detroit, Michigan, USA) (Nguyen et. al, 2021). Among 12 subjects, five of them had maternal pregnancy complications, including short cervix, hypertension and polyhydramnios. After delivery, the placentas of 10 participants were delivered to the pathology department at the DMC to inspect for lesions. Five placentas were found to have chronic or acute lesions, four of which belonged to participants with maternal pregnancy complications. The result showed a significantly higher oxygenation level in the group with an uncomplicated pregnancy compared to those with pregnancy complications. Additionally, significantly lower oxygenation level was observed in those with presence of placental lesions group than those without lesions. Our results suggest the possibility of the relationship between the placental oxygenation level and pregnancy complications and placental pathology. However, the sample size used in this study is small (12 participants) and the placental oxygenation level was only measured in the third trimester. We are now developing a clinical protocol to measure placental oxygenation level in a large population (targeting 1000 pregnant women) of both healthy pregnancy and pregnancy with various underlined complications. Placental oxygenation level will be measured from 20 weeks of pregnancy until delivery in every prenatal care visit. On the other hand, we are upgrading our NIRS device by adding motion sensors to monitor fetal movement. Placental oxygenation level and fetal movement will be used to predict the fetal well-being.In a parallel study with the effect of placental oxygenation on the fetus using the NIRS device, we are developing an algorithm to evaluate the metabolism of placental cells according to oxygen levels using the Dynamic Full-field Optical Coherence Tomography (DFFOCT) system. We verified with HeLa cells similar to Placenta cells that the metabolism of cells can be analyzed by dynamic activity (frequency and magnitude of cells) within a cell and calculate mean frequency which represents the frequencies with high weights. A technology is needed to efficiently distinguish the irregular dynamic activity obtained from numerous cells. As a prior algorithm development, we developed an analysis method for cell death evaluation using four well-known supervised machine learning models on dynamic activity data and an average balanced accuracy of 93.92 0.86% using four well know machine learning models (Logistic Regression, Random Forest, Support vector machine, Gaussian Nave Bayes) (Park et. al, 2022). In the future, we plan to apply this technology to the observation of dynamic activity changes according to oxygen saturation of placenta cells and study the fetus. The worldwide outbreak of novel Coronavirus Disease (COVID-19) has created a massive challenge for researchers and health professionals to increase testing capabilities and alleviate stress on the healthcare system. New tools are needed for diagnostic testing and monitoring under-treatment/observation patients who are infected by the virus. Many commercial wearable devices including the Apple Watch, Fitbit, and Oura ring are all currently being studied for potential use in detecting early signs of viral infection. However, these devices do not assess oxygenation. Low oxygen saturation is an important parameter to consider for respiratory illness. Although pulse oximetry is commonly used to measure arterial tissue oxygenation, NIRS can capture oxygenation from the arteries, veins, capillaries and blood vessels, and is more sensitive to tissue perfusion. We developed a multimodal biosensor device for monitoring parameters associated with physiological changes in respiratory infectious diseases. This device consists of three sensors for Near Infrared Spectroscopy (NIRS), motion and temperature sensing, which can measure tissue oxygenation, body temperature, respiratory functions, and cardiac parameters. The device is being validated over commercial devices in a clinical protocol involving healthy volunteers. The protocol simulates different breathing patterns through a breath holding, a paced breathing, and a hypercapnia task. Preliminary data on fours participant have shown that physiological parameters measured from biosensors devices are consistent with the parameters measured with a commercial device. Change in tissue oxygenation was observed during a stimulated breathing task compared to resting state. However, data needed to be collected on more participants to draw a statistical conclusion. In future work, we are planning to derive a general index that can be used as an indicator of COVID-19 patient well-being.

观察胎盘可展示子宫胎儿环境中的环境。整个妊娠早期胎盘的大小的变化与诸如母体营养不良或贫血等因素的胎盘损伤有关。子宫牙灌注的减少通常与胎儿生长限制（FGR）有关，胎儿未能达到其遗传生长潜力以及相关状况，即先兆子痫。在前露营前的情况下，孕妇通常会患有高血压，尿液中的蛋白质以及视力模糊和头痛等症状，对母亲带来严重的健康风险。另外，前斜率和胎儿生长限制可以增加胎儿围产期死亡和早产的风险。减少子宫腔灌注也可能导致慢性缺氧，这种情况没有充分含氧，胎儿营养不足。这些因素增加了儿童认知障碍的风险，包括脑瘫和终身代谢结果。另外，灌注减少会导致围产期窒息，出生前，期间或立即直接流向胎儿的氧气和血液流动。更严重的窒息病例，胎儿长时间的氧气水平较低，可能会导致对婴儿主要器官（包括大脑，肝脏和肾脏）或器官衰竭和死亡的永久损害。因此，监测胎盘氧合可能有助于区分正常胎儿和患有FGR和/或相关条件的胎儿，并且可能预测妊娠结局。此外，鉴定怀孕期间这种并发症可以允许较早的干预措施，包括降低围产期死亡率的风险（例如西地那非，埃索美拉唑和二甲双胍）和母体基因治疗的药物。尽管对这些干预措施的研究仍处于起步阶段，但在出生前确定妊娠并发症可能会使母亲及其医生采取必要的预防措施。近红外光谱（NIRS）是一种光学方法，用于非侵入性测量血液氧合和脱氧的血红蛋白和深层组织层中的组织氧合，例如大脑，肌肉和胎盘。使用NIR评估胎盘氧合的主要挑战是从器官的解剖位置引起的。考虑到母体胎盘的解剖位置（例如皮肤，脂肪组织，子宫壁），这是一种可穿戴的新型可穿戴深度分辨的NIRS设备，其六个源探测器距离的距离为10-60 mm，旨在探测不同的组织层。通过商业时间域NIRS系统（TRS-41 System，Hamamatsu Photonics，Japan，Japan），在两个人体的两个受试者中进行了确认和验证NIRS设备的性能评估。在两个设备/系统之间发现平均误差为2.7％。然后，使用NIRS装置在底特律医疗中心（DMC，Michigan，Michigan，USA）的植物学研究分支高级产科护理和研究中心的12位志愿者中测量体内胎盘氧合（Nguyen等人，2021年）。在12名受试者中，其中5例患有孕妇妊娠并发症，包括短子宫颈，高血压和多含水症。交付后，将10名参与者的胎盘分娩给DMC病理部门检查病变。发现五个胎盘患有慢性或急性病变，其中四个属于孕妇妊娠并发症的参与者。结果显示，与怀孕并发症的人相比，该组的氧合水平明显更高。另外，在存在胎盘病变组的患者中，观察到的氧合水平明显低于没有病变的人。我们的结果表明，胎盘氧合水平与妊娠并发症与胎盘病理学之间存在关系的可能性。但是，这项研究中使用的样本量很小（12名参与者），胎盘氧合水平仅在三个月中测量。我们现在正在开发一种临床方案，以测量健康怀孕和怀孕的大量人群（针对1000名孕妇）的胎盘氧合水平，并有各种下划线并发症。从怀孕的20周到分娩，每次访问胎盘氧合水平将衡量。另一方面，我们通过添加运动传感器来监视胎儿运动来升级NIRS设备。胎盘氧合水平和胎儿运动将用于预测胎儿的健康。在一项平行研究中，使用NIRS设备对胎盘氧合对胎儿的影响，我们正在开发一种算法，以使用动力学的全面光场光学相干性整体术（Dffoct）（Dfffoct）根据动力学的氧气来评估胎盘细胞的代谢。我们用类似于胎盘细胞的HeLa细胞验证了细胞的代谢，可以通过细胞内的动态活性（细胞的频率和大小）分析，并计算代表高权重频率的平均频率。需要一项技术来有效区分从众多细胞中获得的不规则动态活性。作为先前的算法开发，我们使用四个众所周知的监督机器学习模型在动态活动数据上开发了一种分析方法来评估细胞死亡评估，并使用四个良好的机器学习模型（逻辑回归，随机森林，支持矢量机，高斯nave bayes）的平均平衡精度为93.92 0.86％（Parket。At。2022）。将来，我们计划将该技术应用于胎盘细胞的氧饱和度并研究胎儿的动态活性变化。 全球新型冠状病毒疾病（Covid-19）的爆发为研究人员和卫生专业人员提高测试能力并减轻对医疗保健系统的压力带来了巨大挑战。需要新的工具来诊断和监测受病毒感染的治疗/观察患者。目前正在研究许多商业可穿戴设备，包括Apple Watch，Fitbit和OURA环，用于检测病毒感染的早期迹象。但是，这些设备无法评估氧合。低氧饱和度是考虑呼吸道疾病的重要参数。尽管脉搏血氧饱和度通常用于测量动脉组织氧合，但NIR可以从动脉，静脉，毛细血管和血管中捕获氧合，并且对组织灌注更敏感。我们开发了一种多模式生物传感器设备，用于监测与呼吸道传染病的生理变化相关的参数。该设备由三个用于近红外光谱（NIR），运动和温度传感的传感器组成，它们可以测量组织氧合，体温，呼吸功能和心脏参数。该设备正在通过涉及健康志愿者的临床方案中的商业设备进行验证。该协议通过呼吸，节奏的呼吸和超碳酸盐任务模拟不同的呼吸模式。关于四名参与者的初步数据表明，从生物传感器设备测量的生理参数与用商业设备测量的参数一致。与静止状态相比，在刺激的呼吸任务中观察到组织氧合的变化。但是，需要对更多参与者收集数据才能得出统计结论。在将来的工作中，我们计划得出一个一般指数，该指数可以用作COVID-19患者福祉的指标。