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在表面（300-400 5m 深度）可视化肿瘤微观结构和血管形态，并且只能在占肿瘤总体积一小部分的体积区域上可视化。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频域成像 (OFDI) 仪器，它克服了 MPM 的这些局限性，是一种补充技术。使用多普勒 OFDI，我们将能够在 15 分钟内对最大 5.8 毫米 x 7.8 毫米、深度超过 2 毫米的区域进行成像，与 MPM 相比，图像体积和成像速度均显着增加。该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 拨款的研究，并从长远来看降低我们的研究成本。多普勒 OFDI 仪器将专门用于小动物成像，位于马萨诸塞州综合医院斯蒂尔实验室，其使命是了解实体瘤的病理生理学，并为原发性和转移性癌症开发新颖的治疗方法。多普勒 OFDI 仪器将加速 NIH 十多项研究资助的研究，包括一项计划项目资助、两项生物工程研究合作资助和 3 项 R01 资助。每项资助都依赖于活体成像来探测动物模型中肿瘤的生长、侵袭和对不同实验疗法的反应。例如，计划项目拨款 (P01-CA080124) 依靠 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 OFDI，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使用 MPM 的繁琐的成像方案，并且最多只能实现约 20% 的图像深度。此外，通过多普勒 OFDI，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 OFDI 将促进生理和病理过程的探索以及治疗策略的评估，以对抗癌症的生长和扩散。该设施将由多名研究人员共享，包括麻省总医院放射肿瘤学和皮肤科的科学家，对于实现这些研究人员正在进行的 NIH 资助项目以及许多计划项目的目标至关重要。多普勒 OFDI 将能够解决由于缺乏这种支持技术而尚未得到解答的关键问题，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变化的能力对于确定成功的新型治疗方法来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频域成像仪器，它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。