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: 10266457
• 负责人: Amir H Gandjbakhche
• 金额: $ 79.86万
• 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/10266457
• 关键词: Affect; Algorithms; Anisotropy; Anterior; Artificial Intelligence; Asphyxia; Biological; Biological Phenomena; Biophotonics; Biosensing Techniques; Biosensor; Blood; Blood Vessels; Bluetooth; Breathing; COVID-19; COVID-19 pandemic; Cell physiology; Cells; Cerebral Palsy; Cervical Ripening; Cervix Uteri; Cesarean section; Characteristics; Clinical; Clinical Protocols; Clinical Trials; Collaborations; Colposcopes; Communicable Diseases; Computer Simulation; Consumption; Contralateral; Country; Cushing Syndrome; Data; Defect; Dermis; Devices; Diagnosis; Diagnostic Procedure; Diffuse; Disease Outbreaks; Early Diagnosis; Elements; Epidermis; Excision; Extracellular Matrix; Fatty acid glycerol esters; Fetal Development; Fetal Growth Retardation; Florida; Frequencies; Future; Geometry; Glucose; Goals; Hand; Healthcare Systems; Heart Rate; Hela Cells; Hemoglobin; Home environment; Human; Hypercapnia; Image; Image Analysis; Infection; International; Interruption; Kaposi Sarcoma; Knowledge; Label; Lasers; Lead; Lesion; Light; Lipids; Longitudinal Studies; Machine Learning; Malignant - descriptor; Malignant Neoplasms; Manuals; Measurement; Measures; Membrane; Methodology; Methods; Michigan; Mitochondria; Modeling; Monitor; Monte Carlo Method; Morbidity - disease rate; Movement; Names; National Institute of Child Health and Human Development; Near-Infrared Spectroscopy; Normal tissue morphology; Optical Coherence Tomography; Optics; Organ; Outcome; Oxygen; Oxyhemoglobin; Patients; Pattern; Perinatal; Perinatology; Pharmacotherapy; Physiological; Pilot Projects; Pituitary-dependent Cushing' s disease; Placenta; Play; Pneumonia; Point-of-Care Systems; Polymers; Population Control; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Process; Property; Proteins; Reproduction; Research; Research Personnel; Resolution; Respiration; Respiratory physiology; Role; Sampling; Scanning; Schedule; Scientist; Signal Transduction; Site; Skin; Skin Temperature; Source; Spectrum Analysis; Structure; System; Techniques; Technology; Testing; Thermography; Thermometers; Thick; Time; Tissue imaging; Tissues; Transillumination; Treatment Protocols; Treatment outcome; Triton X100; Ultrasonography; United States National Institutes of Health; Universities; Uterus; Walking; Water; absorption; base; cell fixation; cellular targeting; chromophore; comparative; computerized data processing; density; deoxyhemoglobin; design; detector; experience; experimental study; fetus hypoxia; flexibility; graphical user interface; healthy pregnancy; high risk; imaging system; improved; in vivo; inhibitor/antagonist; instrumentation; multimodality; novel; novel diagnostics; paraform; patient screening; pregnant; recruit; respiratory; response; sensor; simulation; sound; spectrograph; spectroscopic imaging; theories; tissue oxygenation; tomography; tool; user-friendly; volunteer; wearable device

Preterm research Placental oxygenation plays a crucial role in a healthy pregnancy and its outcome. Defects in placenta that affects placental oxygenation can cause preeclampsia and intrauterine growth restriction, fetal hypoxia, asphyxia, and cerebral palsy. A fast and non-invasive method that measures placental oxygenation, quantitatively, sounds necessary to detect such abnormalities. Current methods are either not patient-friendly or time consuming. Therefore, we developed a wearable device using near Infrared Spectroscopy (NIRS) that monitors anterior placenta oxygenation non-invasively and dynamically. This device uses two light sources with 760 nm and 840 nm wavelengths because they are sensitive to changes in blood oxyhemoglobin and deoxyhemoglobin. It consists of two photodiodes as detectors and six LED light sources that are placed in six different distances from 10 to 60 mm away from the LEDs. The different source and detector distances help us scan different tissue depths in order to distinguish between placental oxygenation and maternal layers oxygenation. Also, the probe has a flexible geometry that enables us to place it in proper contact with the skin. For the in-vivo study, we have tested this device on subjects in Detroit Michigan in collaboration with Perinatal Research Branch of NICHD(Dr. Roberto Romero) and Wayne State University, and USUHS. Mentioned study focuses on the baseline placental oxygenation for normal term pregnancies scheduled for cesarean section and Ultra-sound imaging gives us the fat and uterus thicknesses we need for the analysis. Thus far, we have measured placental oxygenation of 12 healthy, singleton, pregnant volunteers (33.33.6 weeks pregnant). We are in the process of completing our measurements on the total of 40 subjects to have adequate statistical power (as one can expect the COVID-19 pandemic has temporarily interrupted this study). The placental oxygenation calculated from two source-detector separations (30mm and 40mm) for this group of 12 subjects ranges from 68% to 89%. However, we found that the calculated placental oxygenation is positively correlated with the thickness of the fat layer. A pregnant woman with a thicker fat layer has a higher placental oxygenation. We believe that this correlation was caused by the highly scattering characteristic of the fat. Hence, we are now performing a Monte Carlo simulation on a five-layer model to correct the effect of maternal layers such as fat on placental oxygenation. These simulations are based on thickness and both scattering and absorption coefficient of all maternal layers (dermis, epidermis, fast, uterus) and placenta. In the other hand, placenta as an essential organ for fetal development and successful reproduction, is the least study organ. Thus, we have also measured the scattering coefficients of the human placenta for the range of 659 to 840nm using a well-established frequency domain diffuse optical spectroscopic system (DOSI) and a lab designed diffuse reflectance device (DRS). Measurements were performed in 8 placentas obtained after cesarean deliveries. Absorption and scattering coefficients were then calculated from the measured reflectance using the random walk theory for DRS and frequency domain algorithm for DOSI. Average reduced scattering coefficient was 0.943 0.015 mm-1 at 760 nm and 0.831 0.009 mm-1 at 840 nm and a power function in the form of 1.6619 (wavelengtht/500 nm)**1.426 was derived for the human placental scattering coefficient. These scattering coefficients can be used to improve measurements of placental oxygen saturation. Along with the in-vivo studies, we are studying placental oxygenation in the cellular level using novel biophotonics method named Dynamic Full Field Optical Coherence Tomography (DFFOCT). These experiments use HeLA cells with manually changed oxygenation. The preliminary results established the ability of DFFOCT to detect the changes in intra-cellular activity for different oxygen level. HeLa cell samples were treated with Triton X-100, which causes membrane permeabilization, and paraformaldehyde, which causes cell fixation. Untreated and treated samples were imaged using DFFOCT and analyzed to determine if DFFOCT could detect cellular activity. We were able to isolate cellular signals from environmental and measure changes in cellular activity following various inhibition treatments. This highlights the potential of DFFOCT to uncover new information about dynamic intracellular fluctuations during various cellular processes. Future experiments with targeted cellular treatments can be conducted to further characterize cellular activity. To identify the biological causes of the untreated signal, controlled experiments involving the removal of cellular energetics via mitochondrial inhibitors and glucose decouplers are planned. Cellular energetics are essential for large polymer buildup, disassembly, movement within the cell, and small protein activity. In another study, we aimed to use the PReterm IMaging system based on colposcope to characterize uterine cervix structure in a longitudinal study of low- and high-risk (prior preterm birth (PTB) or a sonographic short cervix) patients. Polarization imaging is an effective tool to measure optical anisotropy in birefringent materials, such as the cervix's extracellular matrix and to predict cervical ripening and potentially to diagnose pre-term birth. We developed a handheld colposcope device for active polarization imaging of the cervix. Through our under-review collaboration with Wayne State University Perinatology Research Branch and Florida International University we will test our system in a control population and those with PTB prevalence. COVID-19 Biosensor: With the pandemic of COVID-19, in collaboration with Biomedical Optics Lab lead by Dr. Bruce Tromberg, we are using our research in oxygenation quantification to develop a multimodal biosensor for early detection, monitoring and screening patients with respiratory infectious diseases including COVID 19 patients. The COVID-19 pandemic has challenged health care system to develop multimodal biosensing devices to identify patients with physiological signs of a COVID-19 infection. Thus, we are in the process of a clinical protocol approval and ultimately testing a wearable multimodal biosensor. This device consists of a near-infrared spectroscopy (NIRS), a photoplethysmogram (PPG) and a thermometer sensor, capable of monitoring skin temperature, tissue oxygenation level, heart rate and respiratory parameters. Data will be collected through a pilot study using this device in 40 healthy subjects who experienced a breathing pattern similar to that seen in pneumonia using hypercapnia, paced breathing and breath holding. Vital parameters extracted from NIRS signal will be identified that could distinguish between normal versus patterned breathing. In the next few months and as soon as the clinical protocol approved, we will start recruiting and will apply our technology to COVID-19 patients, eventually. Our ultimate goal is to use artificial intelligence and machine learning to identify a pattern of NIRS respiration and tissue oxygenation that would be specific to Corona Virus Disease 2019. The end product is going to be a point-of-case home-accessible device with Bluetooth functionality. Cushing syndrome: We are continuing our research on Cushings syndrome (CS ) in collaboration with SEG at NICHD to test a new hand-held multispectral camera to be used a point-of-care system. The device uses a high-resolution CMOS camera with on-chip filters. Images with resolution of 256X256 pixels are acquired simultaneously at eight different near-infrared wavelengths (700-980 nm). We have also developed a user-friendly graphical interface for data processing in Matlab.

早产研究 胎盘氧合在健康妊娠及其结果中起着至关重要的作用。影响胎盘氧合的胎盘缺陷会导致子痫前期和宫内生长限制，胎儿缺氧，窒息和脑瘫。一种定量测量胎盘氧合的快速和非侵入性方法，这听起来是检测到这种异常所必需的。当前的方法要么不友好，要么耗时。因此，我们使用近红外光谱法（NIR）开发了可穿戴设备，该设备可以非侵入性地和动态地监测前胎盘氧合。该设备使用两个光源，具有760 nm和840 nm波长，因为它们对血液氧血红蛋白和脱氧血红蛋白的变化敏感。它由两个光电二极管组成，作为检测器和六个LED光源，它们位于距离LED 10到60毫米的六个不同距离上。不同的来源和检测器距离有助于我们扫描不同的组织深度，以区分胎盘氧合和孕妇层氧合。此外，探针具有灵活的几何形状，使我们能够将其与皮肤正确接触。 在体内研究中，我们与NICHD（Roberto Romero博士）和Wayne State University和USUHS合作，在底特律密歇根州的受试者上测试了该设备。提到的研究重点是针对针对剖宫产的正常妊娠的基线胎盘氧合，超声检查成像为我们提供了分析所需的脂肪和子宫厚度。到目前为止，我们已经测量了12名健康的，单胎，怀孕志愿者的胎盘氧合（怀孕33.33.6周）。我们正在完成有关40名受试者具有足够统计能力的测量值（因为人们可以期望Covid-19的大流行暂时中断了这项研究）。这组12个受试者的胎盘氧合从两个源检测器分离（30mm和40mm）计算出来，范围为68％至89％。但是，我们发现计算出的胎盘氧合与脂肪层的厚度呈正相关。较厚脂肪层的孕妇具有较高的胎盘氧合。我们认为，这种相关性是由脂肪的高度散射特征引起的。 因此，我们现在正在对五层模型进行蒙特卡洛模拟，以纠正母体层（例如脂肪对胎盘氧合的影响）的影响。这些模拟基于所有母体层（真皮，表皮，快速，子宫）和胎盘的厚度以及散射和吸收系数。 另一方面，胎盘是胎儿发育和成功繁殖的必不可少的器官，是研究器官最少。因此，我们还使用良好的频域分散光学光谱系统（DOSI）和实验室设计的扩散反射器（DRS）测量了659至840nm的人胎盘的散射系数。在剖宫产后获得的8个胎盘进行测量。然后使用DOSI的DR和频域算法的随机行走理论从测得的反射率中计算吸收和散射系数。在760 nm处的平均散射系数为0.943 0.015 mm-1，在840 nm处为0.831 0.009 mm-1，以1.6619（WaveLengtht/500 nm）的形式使用功率函数** 1.426用于人胎盘散射系数。这些散射系数可用于改善胎盘氧饱和度的测量。 除了体内研究外，我们还使用名为Dynamic Full Field Optical光学相干断层扫描（DFFOCT）的新型生物素化学方法研究了细胞水平的胎盘氧合。这些实验使用HeLa细胞手动改变氧合。初步结果确定了DFFOCT检测不同氧水平的细胞内活性变化的能力。用Triton X-100处理HeLa细胞样品，该样品会导致膜通透性和多聚甲醛，从而导致细胞固定。使用DFFOCT对未处理和处理过的样品进行成像，并分析以确定DFFOCT是否可以检测细胞活性。在各种抑制作用治疗后，我们能够从环境中分离细胞信号并测量细胞活性的变化。这突出了DFFOCT在各种细胞过程中发现动态细胞内波动的新信息的潜力。可以进行靶向细胞治疗的未来实验，以进一步表征细胞活性。 为了确定未处理信号的生物学原因，计划通过线粒体抑制剂和葡萄糖去耦进行涉及去除细胞能量的受控实验。细胞能量对于大型聚合物积聚，拆卸，细胞内运动以及小蛋白活性至关重要。 在另一项研究中，我们旨在使用基于阴道镜的早产系统来表征子宫子宫颈结构，这是对低风险和高风险（先前的早产（PTB）或超声范围）患者的纵向研究。极化成像是测量双重材料（例如子宫颈外基质基质）并预测子宫颈成熟并有可能诊断前末期出生的有效工具。我们开发了一种手持式阴道镜设备，用于子宫颈的主动极化成像。通过与韦恩州立大学生态学研究部和佛罗里达国际大学的审视不足合作，我们将在对照人群和PTB患病率的人群中测试我们的系统。 COVID-19-Biosensor： 随着Covid-19的大流行，与Bruce Tromberg博士领导的生物医学光学实验室合作，我们正在使用我们的氧合量化研究研究来开发多模式生物传感器，以早期检测，监测和筛查患有包括Covid 19患者在内的呼吸道感染疾病的患者。 COVID-19大流行对医疗保健系统提出了挑战，以开发多模式的生物传感设备，以鉴定患有COVID-19感染的生理迹象的患者。 因此，我们正在进行临床方案批准的过程中，并最终测试可穿戴的多模式生物传感器。该设备由近红外光谱（NIRS），光插图图（PPG）和温度计传感器组成，能够监测皮肤温度，组织氧合水平，心率和呼吸参数。将通过使用该设备在40名健康受试者中使用该设备的试验研究来收集数据，这些受试者经历了类似于使用HyperCapnia，节奏的呼吸和呼吸的呼吸模式。将确定从NIRS信号中提取的重要参数，可以区分正常呼吸与图案化的呼吸。在接下来的几个月中，临床方案批准后，我们​​将开始招募，并最终将我们的技术应用于Covid-19患者。我们的最终目标是使用人工智能和机器学习来识别针对Corona病毒疾病2019的NIR呼吸和组织氧合的模式。最终产品将是具有蓝牙功能的示例式家庭可访问设备。 库欣综合症： 我们将继续与NICHD的SEG合作进行有关库欣综合症（CS）的研究，以测试一种新的手持多光谱摄像头，以用于护理点系统。该设备使用带有芯片过滤器的高分辨率CMOS摄像头。分辨率为256x256像素的图像以八个不同的近红外波长（700-980 nm）同时获取。我们还开发了一个用户友好的图形接口，用于MATLAB中的数据处理。