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阐明了癌症进展的途径和机制，并推动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来显示表面(300-400 5m深)的肿瘤微结构和血管形态，并且只能在占总肿瘤体积的一小部分的体积区域上显示。此外，由于外源性造影剂的积累，纵向成像的频率往往受到限制。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的这些限制，是一种补充技术。使用多普勒OFDI，我们将能够在15分钟内对宽5.8 mm、宽7.8 mm、深度超过2 mm的区域进行成像，与MPM相比，图像体积和成像速度都有显著提高。成像技术不需要使用示踪剂，允许频繁、重复的时间点测量。这将加快对我们目前资助的NIH赠款的研究，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，安装在马萨诸塞州总医院的斯蒂尔实验室，其任务是了解实体肿瘤的病理生理学，并为原发和转移癌症开发新的根治疗法。多普勒对外直接投资仪器将加快对10多项NIH研究资助的研究，包括1项计划项目资助、2项生物工程研究伙伴资助和3项R01资助。每一笔赠款都依赖于活体成像，以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，计划项目赠款(P01-CA080124)依靠MPM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的繁琐成像方案，并且最多只能获得约20%的图像深度。此外，利用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性的变化。因此，多普勒对外直接投资将有助于探索生理和病理过程以及评估治疗策略，以便与癌症的生长和扩散作斗争。该设施将由多名研究人员共享，其中包括麻省理工学院放射肿瘤科和皮肤科的科学家，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中的项目的目标至关重要。多普勒对外直接投资将使由于缺乏这一使能技术而尚未得到回答的关键问题得到解决，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性、肿瘤血管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以对抗实体癌症的生长和扩散至关重要。到目前为止，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现状的限制。在这项应用中，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，它克服了当前成像技术的许多限制，专门用于在小动物身上评估新型抗癌疗法。

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.