A Quantitative Optical Sensor to Monitor Pre-Clinical Tumor Vascular Physiology

用于监测临床前肿瘤血管生理学的定量光学传感器

• 批准号: 8652715
• 负责人: Nirmala Ramanujam
• 金额: $ 13.54万
• 依托单位: ZENALUX BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8652715
• 关键词: Affect; Animal Model; Animals; Behavior Therapy; Blood Vessels; Breast Cancer Model; Calibration; Clinical Research; Computer software; Computers; Consumption; Coupling; Custom; Detection; Development; Devices; Diffuse; Electronics; Feedback; Fiber Optics; Fluorescence; Fluorescence Spectroscopy; Gases; Generations; Goals; Hemoglobin; Hypoxia; Lead; Light; Literature; Mammary Neoplasms; Marketing; Measurement; Measures; Metabolism; Metric; Mitochondria; Modality; Modeling; Monitor; Mus; Noise; Optics; Outcome; Oxidation-Reduction; Oxygen; Performance; Pharmaceutical Preparations; Phase; Physiological; Physiology; Positioning Attribute; Pre-Clinical Model; Preclinical Drug Evaluation; Property; Public Health; Resolution; Skin; Small Business Technology Transfer Research; Source; Spectrum Analysis; Surface; System; Techniques; Technology; Testing; Time; Tissues; Treatment Efficacy; Tube; Variant; Work; absorption; angiogenesis; antiangiogenesis therapy; base; cancer therapy; charge coupled device camera; cost; design; design and construction; detector; flexibility; in vivo; instrument; laptop; multimodality; neoplastic cell; novel; optical sensor; photomultiplier; pre-clinical; pressure; programs; research clinical testing; response; sensor; tissue phantom; tumor; voltage

Angiogenesis and hypoxia can significantly influence the efficacy of therapy and the behavior of surviving tumor cells. This important fact is supported by a vast amount of literature on pre-clinical models and clinical studies. There is growing demand for technologies to measure tumor hypoxia and angiogenesis temporally and spatially in vivo to enable advances in drug screening, development and optimization. This is particularly useful in the emerging era of anti-angiogenesis and anti-hypoxia therapies. We propose to develop a portable, low power consumption and low-cost, yet accurate and reliable, multimodality optical spectroscopy system with a novel fiber-optic probe to dynamically characterize tumor hypoxia, angiogenesis, and metabolism as well as tissue drug concentration in small animal models without operator bias. The multimodality optical spectroscopy system will be a laptop or battery powered console with the integration of multiple LEDs, a dual-channel spectrometer, a fiber optic probe, electronics and custom software that can be used to perform both diffuse reflectance and fluorescence spectroscopy in vivo. The fiber-optic probe will include an interferometric pressure sensor that can be used to control the probe-tissue pressure for reliable and reproducible spectroscopic measurement of tissue optical properties. The aims of the proposed work (Phase I) will be to (1) design the core technology using LEDs and an interferometric fiber-optic sensor, (2) characterize its performance metrics and (3) validate its utility in a pre-clinical mammary tumor model. This technology will be extended to include quantitative fluorescence measurements in the Phase II STTR project period along with different probe designs to provide flexibility in implementation of this technology to ectopic (tumors grown on flank) and orthotopic models. The commercial device can be marketed as either a single- modality (diffuse reflectance) or a multi-modality (reflectance and fluorescence) device. The outcome of Phase I will lead to a 1st generation Quantilux device which can be productized while the multi-modality 2nd generation device is being refined.The overall objective in Phase II and beyond will be to develop a marketable version of the device and validate its utility for longitudinal tumor therapy monitoring in mouse tumor models.

血管生成和缺氧可以显着影响治疗效果和存活肿瘤细胞的行为。这一重要事实得到了大量有关临床前模型和临床研究的文献的支持。人们对体内时空测量肿瘤缺氧和血管生成的技术的需求不断增长，以促进药物筛选、开发和优化的进步。这在抗血管生成和抗缺氧疗法的新兴时代特别有用。我们建议开发一种便携式、低功耗、低成本、准确可靠的多模态光谱系统，采用新型光纤探头，动态表征小动物模型中的肿瘤缺氧、血管生成和代谢以及组织药物浓度，而不会产生操作员偏差。多模态光谱系统将是一台笔记本电脑或电池供电的控制台，集成了多个 LED、双通道光谱仪、光纤探头、电子设备和定制软件，可用于在体内执行漫反射和荧光光谱。光纤探头将包括一个干涉压力传感器，可用于控制探头组织压力，以对组织光学特性进行可靠且可重复的光谱测量。拟议工作（第一阶段）的目标是 (1) 使用 LED 和干涉光纤传感器设计核心技术，(2) 表征其性能指标，以及 (3) 验证其在临床前乳腺肿瘤模型中的实用性。该技术将扩展到包括第二阶段 STTR 项目期间的定量荧光测量以及不同的探针设计，以便为异位（侧面生长的肿瘤）和原位模型提供该技术实施的灵活性。商业设备可以作为单模态（漫反射）或多模态（反射和荧光）设备进行销售。第一阶段的成果将产生第一代 Quantilux 设备，该设备可以在多模式第二代设备完善的同时进行产品化。第二阶段及以后的总体目标将是开发该设备的适销版本，并验证其在小鼠肿瘤模型中纵向肿瘤治疗监测的实用性。

项目成果

Simultaneous in vivo optical quantification of key metabolic and vascular endpoints reveals tumor metabolic diversity in murine breast tumor models.

• DOI: 10.1002/jbio.201800372
• 发表时间: 2019-04
• 期刊: Journal of biophotonics
• 影响因子: 2.8
• 作者: Zhu C;Li M;Vincent T;Martin HL;Crouch BT;Martinez AF;Madonna MC;Palmer GM;Dewhirst MW;Ramanujam N
• 通讯作者: Ramanujam N

Neglect in Childhood, Problem Behavior in Adulthood.

• DOI: 10.1177/08862605211067008
• 发表时间: 2022-12
• 期刊: JOURNAL OF INTERPERSONAL VIOLENCE
• 影响因子: 2.5
• 作者: Dubowitz, Howard;Roesch, Scott;Lewis, Terri;Thompson, Richard;English, Diana;Kotch, Jonathan B.
• 通讯作者: Kotch, Jonathan B.

Characteristics of Child Maltreatment and Adolescent Marijuana Use: A Prospective Study.

• DOI: 10.1177/1077559515620853
• 发表时间: 2016-02
• 期刊: Child maltreatment
• 影响因子: 5.1
• 作者: Dubowitz H;Thompson R;Arria AM;English D;Metzger R;Kotch JB
• 通讯作者: Kotch JB