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: 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
• 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' 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

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，确保胎儿获得充足的氧气供应。影响其氧饱和度水平的胎盘缺陷可能会导致母亲和婴儿的妊娠结局不佳，包括先兆子痫、胎儿宫内生长受限、胎儿缺氧、窒息和脑瘫。此外，灌注减少可能导致产时窒息，最严重的灌注减少可能导致胎儿死亡。转化生物光子学部分开发了一种可穿戴光学设备，可以连续监测胎盘中的组织氧饱和度。该胎盘氧合监测仪采用深度分辨近红外光谱 (NIRS)，具有 10 - 60 毫米范围内的六种源检测器间隔，这有助于瞄准不同的组织深度。 NIRS 探头灵活且可弯曲，这使得该设备能够正确安装在腹部等弯曲表面上。该装置可以以0.5 Hz的数据采集速率测量实时组织氧饱和度。将组织氧饱和度测量值与商业系统（TRS-41 系统，Hamamatsu Photonics，日本）进行比较，以验证性能。胎盘氧合监测仪产生的氧饱和度水平与商业设备接近 (R2 = 0.94)，平均误差为 2.7% ± 1.8%。根据韦恩州立大学人类调查委员会机构审查委员会 (IRB) 批准的方案 #090717MP4E，胎盘氧合监测仪用于测量位于底特律医疗中心（美国密歇根州底特律市 DMC）围产期研究分部高级产科护理和研究中心的 12 名妊娠晚期单胎孕妇的胎盘组织氧饱和度 （Nguyen 等人，Biomed. Optic Exp.，2021）。其中五名妇女患有孕产妇妊娠并发症。我们的初步结果表明，与正常妊娠的同龄人（75.0% 5.8%）相比，复杂妊娠患者的胎盘组织氧饱和度水平（69.4% 6.7%）显着较低。分娩后，12 名参与者中的 10 名胎盘被送到 DMC 的病理科检查是否有病变。五个胎盘被发现有慢性或急性病变，其中四个属于患有孕产妇妊娠并发症的参与者。我们进一步发现胎盘无病变患者的胎盘氧饱和度（74.2% 5.8%）显着高于有病变的患者（68.7% 5.6%）。这些结果表明胎盘氧饱和度与妊娠并发症和胎盘病理之间存在关系。 基于原有的胎盘氧合监测仪，我们开发了一种带有嵌入式加速度计的新型无线可穿戴多模式胎盘设备。该生物传感器的数据采集速率为20 Hz，可以收集高频信号，例如母体和胎儿心率。添加加速度计来检测胎儿运动。最近，DMC（美国密歇根州底特律）部署了无线胎盘设备，对 24 名妊娠中期和晚期的孕妇进行一次性测量。该队列中的 10 名女性患有母体并发症，包括慢性高血压、哮喘、II 型糖尿病、透析肾衰竭和泌乳素瘤，另外 5 名女性患有严重的先兆子痫。实验过程与之前的测量相同，参与者仰卧在检查床上。分娩后，22 名参与者的胎盘被送往病理实验室检查是否有病变。 17 个胎盘存在问题，包括急性和/或慢性炎症病变、急性绳索炎和血管炎、胎盘梗塞以及与母体血管灌注不良相关的病变。总体而言，所有 24 名参与者均患有孕产妇并发症、胎盘问题和/或新生儿并发症。所有参与者的胎盘平均氧饱和度为68.9±4.2%，与第一次测量时出现母体并发症和/或胎盘病变的孕妇组中发现的氧饱和度水平相似。为了在更大的人群中测试多模式生物传感器，我们正在与 INOVA 费尔法克斯医院的郭阳罗博士合作开发临床方案来监测 1000 多名孕妇的妊娠健康。这项研究最近荣获 2023 财年和 2024 财年科学总监奖。此外，一项临时专利申请（标题：监测妊娠健康的系统和协议，编号 E-198-2022-0-US-01）与多模式生物传感器相关。另一项临时专利申请（标题：计算组织氧饱和度的单源探测器分离方法，编号 E-037-2023-0-US-01）与该研究的方法相关。 DFFOCT：在使用 NIRS 设备研究胎盘氧合影响的同时，我们正在开发一种算法，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（动态全场光学相干断层扫描）系统来实现的。我们的实验涉及使用HeLa细胞，它与胎盘细胞相似，研究结果可以广泛应用。 DFFOCT系统是一种无标记、非侵入性、非破坏性的方法，根据细胞内散射体的运动来分析动态活动。利用 DFFOCT 的优势，我们设计了一种检查细胞动态活性特征的方法（Park, et al. 12(10), 6431-6441, Biomedical Optics Express, 2021），以及自动活力评估技术（Park, et al. 13(6), 3187-3194, Biomedical Optics Express, 2022）。 2023年，我们成功构建了结合DFFOCT系统用于细胞培养的定制培养箱。该培养箱解决了过去在使用 DFFOCT 系统进行扩展细胞观察期间维持最佳“温度”、“气体浓度控制”和“持续供应营养物质”相关的限制。值得注意的是，培养箱对供应的氧气浓度进行系统控制，可以更系统地探索胎盘氧气水平对胎儿发育的影响。我们目前的工作围绕持续采集暴露于不同氧气浓度的 HeLa 细胞的动态活动数据。 多模式生物传感器：2019 年全球冠状病毒大流行（COVID-19 疾病）的出现创造了对远程方法来检测和持续监测传染性呼吸道疾病患者的需求。人们提出了许多不同的设备，包括温度计、脉搏血氧计、智能手表和戒指，来监测家里感染者的症状。然而，这些消费级设备通常无法在白天和夜间进行自动监控。本研究旨在开发一种方法，持续监测呼吸道传染病患者，并利用测量数据和机器学习对呼​​吸模式进行实时分类。与加拿大不列颠哥伦比亚大学的 Babak Shadgan 博士合作，通过不列颠哥伦比亚大学临床研究伦理委员会批准的临床方案，收集了 21 名健康成年志愿者在不同呼吸练习中的数据。收集的数据用于使用随机森林算法对呼吸模式进行分类，分类精度为 87%（Mah 等人，2022）；使用 Pre-ResNet 算法，分类精度为 92.4%（Park 等人，2023）。

项目成果

Modification of a Conventional Deep Learning Model to Classify Simulated Breathing Patterns: A Step toward Real-Time Monitoring of Patients with Respiratory Infectious Diseases.

• DOI: 10.3390/s23125592
• 发表时间: 2023-06-15
• 期刊: Sensors (Basel, Switzerland)
• 作者: Park J;Mah AJ;Nguyen T;Park S;Ghazi Zadeh L;Shadgan B;Gandjbakhche AH
• 通讯作者: Gandjbakhche AH

Structured sparse multiset canonical correlation analysis of simultaneous fNIRS and EEG provides new insights into the human action-observation network.

• DOI: 10.1038/s41598-022-10942-1
• 发表时间: 2022-04-27
• 期刊: Scientific reports
• 影响因子: 4.6

Monitoring LITT thermal penetration depth using real-time analysis of backscattered light.

• DOI: 10.1002/jbio.201200082
• 发表时间: 2014-06
• 期刊: Journal of biophotonics
• 影响因子: 2.8
• 作者: Shacham R;Steinberg I;Gandjbakhche AH;Gannot I
• 通讯作者: Gannot I

Using in-vivo fluorescence imaging in personalized cancer diagnostics and therapy, an image and treat paradigm.

• DOI: 10.1177/153303461101000605
• 发表时间: 2011-12
• 期刊: Technology in cancer research & treatment
• 影响因子: 2.8
• 作者: Ardeshirpour Y;Chernomordik V;Capala J;Hassan M;Zielinsky R;Griffiths G;Achilefu S;Smith P;Gandjbakhche A
• 通讯作者: Gandjbakhche A

Cerebral hemodynamic response during a live action-observation and action-execution task: A fNIRS study.

• DOI: 10.1371/journal.pone.0253788
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Miguel HO;Condy EE;Nguyen T;Zeytinoglu S;Blick E;Bress K;Khaksari K;Dashtestani H;Millerhagen J;Shahmohammadi S;Fox NA;Gandjbakhche A
• 通讯作者: Gandjbakhche A