Three-Dimensional Tissue Dynamics Imaging

1263753 Nolte拟议的研究将开发一种多模式成像系统，集成TDI与同步共焦和低相干反向散射成像。共聚焦通道的分子特异性，以及反向散射通道的细胞和核形态学变化，将用于验证TDI并识别与药物反应TDS谱图中观察到的特征相对应的生物学机制。他们将使用多通道系统来研究两类众所周知的化合物：线粒体毒素和Raf激酶抑制剂。TDI然后将被应用于研究细胞凋亡/坏死，有丝分裂/胞质分裂和生化/生物力学振荡。这些过程是药物疗效的重要标志，并呈现强烈的生理反应，使其非常适合动态成像研究。本研究将建立通过组织动态成像检测的细胞内运动的类型、对不同类型药物作用机制的灵敏度和特异性。TDI将能够跟踪组织的生理反应，从而能够发现新的动态过程并增强组织尺度生物动力学的知识。拟议研究的成功完成将为组织动力学成像奠定基础，成为一种独特的成像工具，具有广泛的未来生物医学应用。这些潜在的应用包括发现对消费者具有较低副作用和较低成本的新候选药物，选择专门针对患者的癌症化疗以改善癌症缓解和患者生活质量，以及提高体外受精的成功率，以降低医疗成本和消除多胞胎的医疗并发症。由生物基础设施部（DBI）通过生物研究仪器开发（IDBR）计划和化学，生物工程，环境和运输系统部（CBET）资助。

1263753NolteThe proposed research will develop a multimodal imaging system that integrates TDI with simultaneous confocal and low-coherence backscatter imaging. The molecular specificity of the confocal channel, and the cellular and nuclear morphology changes from the backscatter channel, will serve to validate TDI and identify the biological mechanisms that correspond to the features observed in drug-response TDS spectrograms. They will use the multichannel system to study two well-known classes of compounds: mitochondrial toxins and Raf kinase inhibitors. TDI then will be applied to study apoptosis/necrosis, mitosis/cytokinesis and biochemical/biomechanical oscillations. These processes are important markers for drugefficacy and present strong physiological responses that make them ideally suited to study withdynamic imaging. This research will establish the types of intracellular motion that are detected by tissue dynamic imaging, the sensitivity, and the specificity to different types of mechanism of drug action. TDI will be able to track physiological responses of tissue, enabling discovery of new dynamic processes and enhancing knowledge of tissue-scale biodynamics. The successful completion of the proposed research will lay the foundation for tissue dynamics imaging to become a unique imaging tool with a broad array of future biomedical applications. These potential applications include the discovery of new drug candidates with lower side effects and lower costs to consumers, the selection of cancer chemotherapy specifically tuned to the patient to improve cancer remission and patient quality of life, and improvement in the success rate of in vitro fertilization to reduce health-care costs and remove medical complications of multiple births.This award is co-funded by the Division of Biological Infrastructure (DBI) through the Instrument Development for Biological Research (IDBR) program, and by the Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET).