Quantitative Biophotonics for Tissue Characterization and Function

用于组织表征和功能的定量生物光子学

基本信息

批准号：
10913894
负责人：
Amir H Gandjbakhche
金额：
$ 103.43万
依托单位：
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
依托单位国家：
美国
项目类别：
财政年份：
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/10913894
关键词：
Abdomen Accelerometer Acute Address Adult Affect Algorithms Asphyxia Asthma Award Beds Behavior Biological Phenomena Biophotonics Biosensor Blood Vessels Breathing Breathing Exercises British Columbia COVID-19 COVID-19 outbreak Canada Cells Cerebral Palsy Chronic Classification Clinical Clinical Protocols Clinical Research Clinical Trials Collaborations Collection Communicable Diseases Computer Simulation Contralateral Country Data Defect Devices Diagnostic Procedure Diffuse Disease Elements Ensure Evaluation Exposure to Fetal Death Fetal Development Fetal Growth Retardation Fetal Heart Rate Fetal Movement Fetus Frequencies Gases Hela Cells Hemoglobin Home Hospitals Human Hypertension Image Image Analysis Incubators Individual Institutional Review Boards Investigation Japan Kaposi Sarcoma Kidney Failure Knowledge Label Lasers Legal patent Lesion Lipids Machine Learning Malignant - descriptor Malignant Neoplasms Maternal complication Measurement Measures Medical center Metabolic Methodological Studies Methodology Methods Michigan Modeling Monitor Morbidity - disease rate Mothers Movement Near-Infrared Spectroscopy Neonatal Non-Insulin-Dependent Diabetes Mellitus Normal tissue morphology Nutrient Optical Coherence Tomography Optics Oxygen Participant Pathology Patient Monitoring Patients Pattern Performance Perfusion Perinatology Pharmacotherapy Physiologic pulse Physiological Pituitary-dependent Cushing&apos s disease Placenta Placental Infarction Play Population Pre-Eclampsia Pregnancy Pregnancy Complications Pregnancy Outcome Pregnant Women Procedures Prolactinoma Property Protocols documentation Research Research Ethics Research Personnel Respiratory Disease Respiratory physiology Role Scientist Second Pregnancy Trimester Signal Transduction Site Source Spectrum Analysis Supine Position Surface Symptoms System Techniques Technology Temperature Testing Thermography Thermometers Third Pregnancy Trimester Time Tissue imaging Tissues Transillumination Traumeel S Treatment Protocols Treatment outcome United States National Institutes of Health Universities Vasculitis Walking Water Woman absorption chromophore cohort comparative coronavirus pandemic data acquisition density deoxyhemoglobin design detector experimental study fetus hypoxia flexibility healthy pregnancy instrumentation intrapartum multimodality novel diagnostics obstetric care peer photonics pregnancy health random forest respiratory response smart watch spectrograph theories time use tissue oxygenation tomography trait volunteer wearable sensor technology wireless

项目摘要

Placental oxygenation plays a crucial role in a healthy pregnancy, ensuring the fetus receives an adequate supply of oxygen. Defects in the placenta that affects its oxygen saturation level can lead to poor pregnancy outcomes for both the mother and baby, including preeclampsia, intrauterine fetal growth restriction, fetal hypoxia, asphyxia, and cerebral palsy. Additionally, reduced perfusion could cause intrapartum asphyxia and the most severe reduction of perfusion could lead to fetal death. The Section on Translational Biophotonics has developed a wearable optical device to monitor tissue oxygen saturation in the placenta continuously. This placental oxygenation monitor utilizes depth-resolved near-infrared spectroscopy (NIRS) and features six source-detector separations ranging from 10 - 60 mm, which is helpful to target different tissue depths. The NIRS probe is flexible and bendable, which allows the device to fit properly on a curved surface like an abdomen. This device can measure real-time tissue oxygen saturation at a data acquisition rate of 0.5 Hz. Measurements of tissue oxygen saturation were compared with a commercial system (TRS-41 system, Hamamatsu photonics, Japan) to validate performance. The placental oxygenation monitor yields close oxygen saturation levels with the commercial device (R2 = 0.94) with an averaged error of 2.7% 1.8%. Under protocol #090717MP4E, which was approved by the Wayne State University Human Investigations Committee Institutional Review Board (IRB), the placental oxygenation monitor was used to measure tissue oxygen saturation in the placenta of 12 singleton pregnant women in their third trimester 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., Biomed. Optic Exp., 2021). Five of these women had maternal pregnancy complications. Our preliminary results have indicated a significantly lower tissue oxygen saturation level in the placenta of patients with complicated pregnancies (69.4% 6.7%) compared to their peers with normal pregnancies (75.0% 5.8%). After delivery, 10 of the 12 participants placentas 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. We further found that patients with lesion-free placentas presented a significantly higher placental oxygen saturation (74.2% 5.8%) than patients with lesions (68.7% 5.6%). These results suggest a relationship between the placental oxygen saturation and pregnancy complications and placental pathology. Based on the original plancental oxygenation monitor, we have developed a new wireless and wearable multimodal placental device with an embeded accelerometer. The biosensor has a data acquisition rate of 20 Hz, which allows collection of high frequency signals such as maternal and fetal heart rates. The accelerometer was added to detect fetal movement. The wireless placenta-device has recently been deployed to perform a one-time measurement of 24 pregnant women at their second and third trimesters at DMC (Detroit, Michigan, USA). Ten of the women in this cohort had maternal complications including chronic hypertension, asthma, type II diabetes, renal failure with dyalisis, and prolactinoma, and five had preeclampsia with severe features. The experimental procedure was perfomed in the same way as the previous measurement, where the participant lied down on the examination bed in a supine position. After delivery, the placentas of 22 participants were sent to a pathology labratory to examine for lesions. Seventeen placentas had issues including acute and/or chronic inflammartory lesions, acute funisitis and vasculitis, placental infarct, and lesions associated with maternal vascualar malperfusion. In general, all 24 participants had either maternal complications, placental issues, and/or neonatal complications. The average oxygen saturation of the placenta of all participants were 68.9 4.2%, which was similar to the oxygen saturation level found in the group of pregnant women with maternal complications and/or placental lesions in the first measurment. In order to test the multimodal biosensor in a larger population, we are collaborating with Dr. Guoyang Luo at the INOVA Fairfax Hospital to develop a clinical protocol to monitor pregnancy health in more than 1000 pregnant women. This research was recently awarded with the Scientific Director Award for FY 2023 & FY 2024. In addition, a provisional patent application (Title: System and protocol for monitoring pregnancy health, No. E-198-2022-0-US-01) is associated with the multimodal biosensor. An additional provisional patent application (Title: Single source-detector separation approach to calculate tissue oxygen saturation, No. E-037-2023-0-US-01) is associated with the methodology of the study. DFFOCT: In tandem with our research into the impact of placental oxygenation using the NIRS device, we are concurrently developing an algorithm that assesses the metabolic behavior of placental cells based on varying oxygen levels. This is accomplished through the utilization of the DFFOCT (Dynamic Full-field Optical Coherence Tomography) system. Our experimentation involves employing HeLa cells, which are similar to placental cells and the results of the study can be widely applied. The DFFOCT system is a label-free, non-invasive, and non-destructive method that analyzes the dynamic activity based on the movement of the scattering body within the cell. Capitalizing on the strengths of DFFOCT, we have devised a methodology for scrutinizing the dynamic activity traits of cells (Park, et al. 12(10), 6431-6441, Biomedical Optics Express, 2021), alongside an automated viability evaluation technology (Park, et al. 13(6), 3187-3194, Biomedical Optics Express, 2022). In 2023, we successfully constructed a customized incubator for cell cultivation in conjunction with the DFFOCT system. This incubator addresses past limitations associated with maintaining optimal 'temperature', 'gas concentration control', and the 'continuous supply of nutrients' during extended cell observations using the DFFOCT system. Notably, the incubator's systematic control over the supplied O2 concentration enables a more methodical exploration of the impact of placental oxygen levels on fetal development. Our current efforts revolve around the ongoing acquisition of dynamic activity data from HeLa cells exposed to varying O2 concentrations. Multimodal biosensor: The emergence of the global coronavirus pandemic in 2019 (COVID-19 disease) created a need for remote methods to detect and continuously monitor patients with infectious respiratory diseases. Many different devices, including thermometers, pulse oximeters, smartwatches, and rings, were proposed to monitor the symptoms of infected individuals at home. However, these consumer-grade devices are typically not capable of automated monitoring during both day and night. This study aims to develop a method to continuously monitor patients with respiratory infectious disease and classify breathing patterns in real-time using the measured data and Machine Learning.In a collaboration with Dr. Babak Shadgan at the University of British Columbia, Canada, data were collected in 21 healthy adult volunteers during different breathing exercises through a clinical protocol approved by the Clinical Research Ethics Board at the University of British Columbia. Collected data was used to classify breathing patterns using Random Forest algorithm, which results in a classification accuracy of 87% (Mah et al., 2022) and using Pre-ResNet, which results in a classification accuracy of 92.4% (Park et al., 2023).

胎盘氧合在健康妊娠中起着至关重要的作用，从而确保胎儿获得足够的氧气供应。胎盘中影响其氧饱和度水平的缺陷会导致母亲和婴儿的妊娠结局不佳，包括先兆子痫，宫内胎儿胎儿生长限制，胎儿缺氧，窒息和脑瘫。此外，灌注减少可能导致沥青内部窒息，灌注最严重的降低可能导致胎儿死亡。关于翻译生物光子学的部分已经开发了可穿戴的光学设备，可连续监测胎盘中的组织氧饱和度。该胎盘氧合监测器利用深度分辨的近红外光谱（NIR），具有六个源检测器分离范围为10-60 mm，这有助于靶向不同的组织深度。 NIRS探针是柔性且弯曲的，可以使设备像腹部一样正确地贴在弯曲的表面上。该设备可以以0.5 Hz的数据采集速率测量实时组织氧饱和度。将组织氧饱和度的测量与商业系统（TRS-41系统，Hamamatsu光子学，日本）进行了比较，以验证性能。胎盘氧合监测器可通过商业装置（R2 = 0.94）产生接近氧饱和度水平，平均误差为2.7％1.8％。根据协议＃090717MP4E，该协议获得了韦恩州立大学人类调查委员会的机构审查委员会（IRB）的批准，使用胎盘氧合监测仪来测量12个Singleton孕妇在其第三个三生中的胎盘中的胎盘中的组织氧饱和度，该中心是高发中心和perinotrot intro Introit Chartron Classory Chartro Insuit Chartro Indro Intro Insuit Chartro Insery Clanser Inderroit Clysroits instro Insuit unsroit Chansroit Clysroit Clysroit（DMC）（DM）（Nguyen等人，BioMed。MiticExp。，2021）。这些妇女中有五个患有孕妇怀孕并发症。我们的初步结果表明，与正常妊娠（75.0％5.8％）相比，复杂妊娠患者（69.4％6.7％）的胎盘（69.4％6.7％）的组织氧饱和度显着降低。交付后，在12名参与者中，有10个被送到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。我们进一步发现，无病变的胎盘患者的胎盘氧饱和度（74.2％5.8％）明显高于病变患者（68.7％5.6％）。这些结果表明胎盘氧饱和度与妊娠并发症与胎盘病理学之间存在关系。基于原始的平原氧合监视器，我们开发了带有嵌入加速度计的新的无线和可穿戴的多模式设备。生物传感器的数据采集速率为20 Hz，允许收集高频信号，例如母体和胎儿心率。添加加速度计以检测胎儿运动。最近已部署了无线胎盘装备，以对DMC（美国密歇根州底特律）的第二和第三个三个孕妇进行一次性测量。该队列中的十名女性患有母体并发症，包括慢性高血压，哮喘，II型糖尿病，染色体肾衰竭和催乳素瘤，五个患者具有严重特征的先兆子痫。实验程序的完善方式与以前的测量相同，在该测量中，参与者在仰卧位置躺在考试床上。分娩后，将22名参与者组成的胎盘被送到病理缩写症中以检查病变。十七个胎盘存在问题，包括急性和/或慢性炎性病变，急性炎症炎和血管炎，胎盘梗塞以及与母体Vascualar malperfusion相关的病变。通常，所有24名参与者都有产妇并发症，胎盘问题和/或新生儿并发症。所有参与者的胎盘的平均氧饱和度均为68.9 4.2％，这与在第一个测量中患有母体并发症和/或胎盘病变的孕妇中发现的氧饱和度水平相似。为了在较大人群中测试多模式生物传感器，我们正在与Inova Fairfax医院的圭阳Luo博士合作，开发了一项临床方案，以监测1000多名孕妇的妊娠健康。该研究最近获得了2023财年和2024财年科学总监奖。此外，临时专利申请（标题：监测妊娠健康的系统和协议，E-198-2022-0-US-01号）与多模式生物传感器有关。另一种临时专利应用（标题：计算组织氧饱和度的单源检测分离方法，编号E-037-2023-0-US-01）与研究的方法相关。 dffoct：在我们对使用NIRS设备胎盘氧合的影响的研究中，我们同时开发了一种算法，该算法根据不同的氧水平评估胎盘细胞的代谢行为。这是通过使用DFFOCT（动态全场光学连贯断层扫描）系统来实现的。我们的实验涉及使用与胎盘细胞相似的HeLa细胞，并且可以广泛应用研究结果。 DFFOCT系统是一种无标签，非侵入性和非破坏性方法，可根据细胞内散射体的运动来分析动态活性。利用DFFOCT的优势，我们设计了一种方法来审查细胞的动态活性特征（Park等，第12（10），6431-6441，生物医学光学器件，2021年，2021年），以及自动化的生存能力评估技术（Park等人13（6），3187-3187-312194，SEACTICIC，SEARTICED，SERTERICS，SERTEDICS，SERTEDICS，SEACTICAIL，SERVERICS，SEACTICAICS，SYSED222194，SONDICED，SONDICED，SONSED SODICED，SONSEDSICED，SONSEDSICED。在2023年，我们成功构建了一个定制的孵化器，用于与DFFOCT系统结合使用。该孵化器解决了使用DFFOCT系统在扩展细胞观测过程中维持最佳“温度”，“气体浓度控制”和“持续营养供应”相关的过去局限性。值得注意的是，孵化器对所提供的O2浓度的系统控制可以对胎盘氧水平对胎儿发育的影响进行更有条理的探索。我们目前的努力围绕着从暴露于不同O2浓度的HELA细胞中持续获取动态活性数据。多模式生物传感器：2019年全球冠状病毒大流行的出现（Covid-19疾病）提出了远程方法检测并连续监测感染性呼吸道疾病患者的远程方法。提出了许多不同的设备，包括温度计，脉搏血氧仪，智能手表和环，以监测家里感染者的症状。但是，这些消费级设备通常在白天和黑夜都无法自动监控。这项研究旨在开发一种方法，以连续监测呼吸道感染性疾病的患者，并使用测量的数据和机器学习对呼吸模式进行实时分类。收集的数据用于使用随机森林算法对呼吸模式进行分类，该算法的分类准确性为87％（Mah等，2022），并使用Pre-Resnet进行了分类，从而导致92.4％的分类准确性（Park等，2023）。