Doppler Optical Frequency Domain Imaging Instrument

描述（申请人提供）：多光子显微镜（MPM）在体内实体肿瘤生物学研究中的应用已经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肿瘤微观结构和血管形态的表面可视化（300-400 5m深度），并且只能覆盖肿瘤总体积的一小部分体积区域。此外，由于外源性造影剂的积累，纵向成像的频率往往有限。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的这些限制，是一种互补技术。使用多普勒OFDI，我们将能够在15分钟内成像5.8 mm × 7.8 mm，深度超过2mm的区域，与MPM相比，图像体积和成像速度都有显着提高。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，并安置在马萨诸塞州总医院的斯蒂尔实验室，该实验室的任务是了解实体肿瘤的病理生理学，并为原发性和转移性癌症开发新的治疗方法。多普勒OFDI仪器将加速十多项NIH研究补助金的研究，包括一项计划项目补助金，两项生物工程研究伙伴补助金和3项R01补助金。每笔拨款都依赖于活体成像来探测动物模型中肿瘤对不同实验疗法的生长、侵袭和反应。例如，计划项目拨款（P01-CA080124）依靠MPM来监测不同分子干预和治疗方法对血管正常化的反应。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繁琐的MPM成像方案，最多只能达到图像深度的20%左右。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将有助于探索生理病理过程和评估治疗策略，以对抗癌症的生长和扩散。该设施将由多名研究人员共享，包括来自MGH放射肿瘤学和皮肤病学部门的科学家，并且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OFDI将允许解决由于缺乏这种使能技术而无法回答的关键问题，并将开辟新的研究途径，使我们更接近癌症的新疗法。

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.