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.

观察胎盘可以了解子宫内胎儿的环境。妊娠早期胎盘大小的变化与母亲营养不良或贫血等因素造成的胎盘损伤有关。子宫胎盘灌注减少通常与胎儿生长受限（FGR）有关，这是一种胎儿未能达到其遗传生长潜力的情况，以及相关的先兆子痫。在先兆子痫的情况下，孕妇通常会有高血压，尿液中含有蛋白质，以及视力模糊和头痛等症状，对母亲构成重大的健康风险。此外，先兆子痫和胎儿生长受限可增加胎儿围产期死亡和早产的风险。子宫胎盘灌注减少也可导致慢性缺氧，即组织充氧不足和胎儿营养不良。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后果。此外，灌注减少可导致围产期窒息，即胎儿在出生前、出生前或出生前立即缺氧和血流量不足。在更严重的窒息情况下，胎儿长时间处于低氧状态，可能会对婴儿的主要器官造成永久性损害，包括大脑、肝脏和肾脏，或器官衰竭和死亡。因此，监测胎盘氧合可能有助于区分正常胎儿和FGR及/或相关疾病胎儿，并可能预测妊娠结局。此外，在怀孕期间识别此类并发症可以进行早期干预，包括降低围产期死亡风险的药物（例如，西地那非、埃索美拉唑和二甲双胍）和母体基因治疗。虽然对这些干预措施的研究仍处于起步阶段，但在出生前识别妊娠并发症可能使母亲及其医生采取必要的预防措施。近红外光谱（NIRS）是一种非侵入性测量血液含氧和脱氧血红蛋白以及深层组织层（如大脑、肌肉和胎盘）组织氧合的光学方法。使用近红外光谱评估胎盘氧合的主要挑战来自于器官的解剖位置。考虑到母体胎盘的解剖位置（如皮肤、脂肪组织、子宫壁），设计了一种新型的可穿戴深度分辨近红外装置，该装置具有6个距离为10-60 mm的源探测器，可探测不同的组织层。使用商用时域NIRS系统（TRS-41系统，Hamamatsu photonics，日本）在两名受试者的身体多个部位（包括双臂、小腿和腹部）确认并验证了NIRS装置的性能评估。两个设备/系统之间的平均误差为2.7%。然后使用NIRS设备测量位于底特律医疗中心（DMC, Detroit, Michigan， USA）围产期研究分院高级产科护理和研究中心的12名志愿者的体内胎盘氧合情况（Nguyen et al ., 2021）。12例受试者中，5例存在宫颈短、高血压、羊水过多等孕产妇妊娠并发症。分娩后，10名参与者的胎盘被送到DMC的病理部门检查病变。5个胎盘被发现有慢性或急性病变，其中4个属于产妇妊娠并发症的参与者。结果显示，与妊娠并发症组相比，无并发症妊娠组的氧合水平明显更高。此外，有胎盘病变组的氧合水平明显低于无胎盘病变组。我们的结果提示胎盘氧合水平与妊娠并发症和胎盘病理之间的可能关系。然而，本研究中使用的样本量很小（12名参与者），并且仅在妊娠晚期测量胎盘氧合水平。我们目前正在制定一项临床方案，以测量大量人群（目标为1000名孕妇）的胎盘氧合水平，包括健康妊娠和各种突出并发症的妊娠。胎盘氧合水平将测量从怀孕20周至分娩在每次产前护理访问。另一方面，我们正在升级我们的近红外光谱仪设备，增加运动传感器来监测胎儿的运动。胎盘氧合水平和胎儿运动将用于预测胎儿的健康状况。在使用近红外光谱（NIRS）设备进行胎盘氧合对胎儿影响的平行研究中，我们正在开发一种算法，利用动态全视野光学相干断层扫描（DFFOCT）系统根据氧水平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动（细胞的频率和大小）来分析，并计算出代表高权重频率的平均频率。需要一种技术来有效地区分从大量细胞中获得的不规则动态活动。作为之前的算法开发，我们开发了一种细胞死亡评估的分析方法，使用四种知名的监督机器学习模型对动态活动数据进行评估，并使用四种知名的机器学习模型（逻辑回归，随机森林，支持向量机，高斯中贝叶斯）的平均平衡精度为93.92 0.86% （Park et. al ., 2022）。在未来，我们计划将该技术应用于观察胎盘细胞根据氧饱和度的动态活性变化，并对胎儿进行研究。