Doppler Optical Frequency Domain Imaging Instrument

多普勒光频域成像仪

• 批准号: 7793981
• 负责人: Dai Fukumura
• 金额: $ 25.96万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7793981
• 关键词: Address; Anesthesia procedures; Animal Model; Animals; Arts; Biomedical Engineering; Blood; Blood Vessels; Cell Survival; Contrast Media; Dermatology; Disseminated Malignant Neoplasm; Evaluation; Experimental Neoplasms; Frequencies; Functional disorder; Funding; General Hospitals; Grant; Growth; Housing; Image; Imaging Techniques; Imaging technology; Intervention; Investigational Therapies; Laboratories; Lead; Lymphatic vessel; Malignant Neoplasms; Massachusetts; Measurement; Microscopy; Mission; Molecular; Monitor; Morphology; Optics; Pathologic Processes; Pathway interactions; Physiological; Program Research Project Grants; Protocols documentation; Radiation Oncology; Research; Research Personnel; Research Project Grants; Resolution; Scientist; Solid; Solid Neoplasm; Speed; Technology; Tissue Viability; Tracer; Tumor Biology; Tumor Tissue; Tumor Volume; Tumor-Associated Vasculature; United States National Institutes of Health; anti-cancer therapeutic; cancer therapy; combat; cost; fighting; in vivo; instrument; meetings; neoplastic cell; novel; novel therapeutic intervention; novel therapeutics; public health relevance; response; treatment strategy; tumor; tumor progression

DESCRIPTION (provided by applicant): The application of multiphoton microscopy (MPM) to the study of solid tumor biology in vivo has elucidated pathways and mechanisms of cancer progression and has motivated new therapeutic strategies and approaches. Current high-resolution intravital imaging techniques, however, can only be used to visualize tumor microstructure and vascular morphology superficially (300-400 5m depth) and only over volumetric regions that are a fraction of the total tumor volume. Additionally, longitudinal imaging is often limited in frequency due to the accumulation of exogenous contrast agents. Here we propose to purchase a state-of-the- art Doppler Optical Frequency Domain Imaging (OFDI) instrument, which overcomes these limitations of MPM and is a complementary technology. Using Doppler OFDI, we will be able to image a field up to 5.8 mm by 7.8 mm and more than 2 mm deep in 15 minutes, a significant increase both image volume and imaging speed compared to MPM. The imaging technique does not require the use of tracers, allowing for frequent, repeated timepoint measurements. This will accelerate research on our currently funded NIH grants and reduce the cost of our research over the long term. The Doppler OFDI instrument would be dedicated to small animal imaging and housed in the Steele Laboratories at Massachusetts General Hospital, whose mission is to understand the pathophysiology of solid tumors and develop novel, curative therapies for primary and metastatic cancers. The Doppler OFDI instrument will accelerate research on more than ten NIH research grants, including one Program Project Grant, two Bioengineering Research Partnership Grants and 3 R01 grants. Each grant relies upon intravital imaging to probe the growth, invasion and response of tumors to different experimental therapies in animal models. As an example, the Program Project Grant (P01-CA080124) relies upon MPM to monitor vascular normalization in response to different molecular interventions and treatment approaches. Using Doppler OFDI, we will evaluate vascular changes throughout the entire experimental tumor, which would normally require prolonged anesthesia and cumbersome imaging protocols using MPM and would only achieve about 20% of the image depth at best. Furthermore, with Doppler OFDI we will be able to monitor changes in tumor associated lymphatic vessels and changes in tumor tissue viability. Thus Doppler OFDI will facilitate the exploration of physiological and pathological processes and the evaluation of treatment strategies in order to fight the growth and spread of cancer. The facility will be shared by multiple investigators, including scientists from the Departments of Radiation Oncology and Dermatology at MGH, and will be critical for meeting the aims of ongoing NIH-funded projects of these investigators as well as many planned projects. Doppler OFDI will allow critical questions to be addressed that have not been answered due to the lack of this enabling technology and will open new avenues of research that will lead us closer to new therapies for cancer. Public Health Relevance: The ability to monitor and interrogate changes in tumor cell viability, tumor blood vasculature and tumor associated lymphatic vessels is critical to identify successful novel therapeutic approaches to combat the growth and spread of solid cancers. To date, the ability to monitor these parameters with the necessary spatial and temporal resolution has been limited by the current state of the imaging technology. In this application, we propose to purchase a novel state-of-the-art Doppler optical frequency domain imaging instrument, which overcomes many of the limitations of current imaging technologies, for dedicated use in the evaluation of novel anti-cancer therapeutics in small animals.

描述（由申请人提供）：多光子显微镜（MPM）在体内实体瘤生物学研究中的应用阐明了癌症进展的途径和机制，并激发了新的治疗策略和方法。然而，目前的高分辨率活体成像技术只能用于表面（300-400 5 m深度）和仅在占总肿瘤体积的一部分的体积区域上可视化肿瘤微观结构和血管形态。此外，由于外源性造影剂的积累，纵向成像的频率通常受到限制。在这里，我们建议购买最先进的多普勒光学频域成像（OFDI）仪器，它克服了MPM的这些限制，是一种补充技术。使用多普勒对外直接投资，我们将能够在15分钟内对5.8 mm × 7.8 mm的区域进行成像，深度超过2 mm，与MPM相比，成像体积和成像速度都有显着增加。成像技术不需要使用示踪剂，允许频繁重复的时间点测量。这将加速我们目前资助的NIH赠款的研究，并降低我们长期研究的成本。多普勒对外直接投资仪器将专门用于小动物成像，并设在马萨诸塞州总医院的斯蒂尔实验室，其使命是了解实体肿瘤的病理生理学，并开发治疗原发性和转移性癌症的新疗法。多普勒对外直接投资工具将加快对10多项NIH研究赠款的研究，包括一项计划项目赠款、两项生物工程研究伙伴关系赠款和3项R 01赠款。每项资助都依赖于活体成像来探测肿瘤的生长、侵袭和对动物模型中不同实验疗法的反应。例如，计划项目补助金（P01-CA 080124）依赖于MPM来监测血管正常化，以响应不同的分子干预和治疗方法。使用多普勒对外直接投资，我们将评估整个实验肿瘤的血管变化，这通常需要长时间的麻醉和繁琐的成像协议，使用MPM，最多只能达到约20%的图像深度。此外，通过多普勒对外直接投资，我们将能够监测肿瘤相关淋巴管的变化和肿瘤组织活力的变化。因此，多普勒对外直接投资将有助于探索生理和病理过程，评估治疗战略，以防止癌症的生长和扩散。该设施将由多名研究人员共享，包括来自MGH放射肿瘤学和皮肤病学部门的科学家，对于满足这些研究人员正在进行的NIH资助项目以及许多计划中的项目的目标至关重要。多普勒对外直接投资将有助于解决由于缺乏这一技术而尚未得到解决的关键问题，并将开辟新的研究途径，使我们更接近癌症的新疗法。 公共卫生相关性：监测和询问肿瘤细胞活力、肿瘤血管系统和肿瘤相关淋巴管的变化的能力对于确定成功的新型治疗方法以对抗实体癌的生长和扩散至关重要。迄今为止，以必要的空间和时间分辨率监测这些参数的能力受到成像技术的当前状态的限制。在本申请中，我们建议购买一种新型的最先进的多普勒光学频域成像仪器，该仪器克服了当前成像技术的许多局限性，专门用于评估小动物的新型抗癌疗法。