Preclinical Time domain Fluorescence Tomography Platform

临床前时域荧光断层扫描平台

• 批准号: 10064024
• 负责人: Anand T.N. Kumar
• 金额: $ 4.67万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10064024
• 关键词: 3-Dimensional; 4T1; Adoption; Algorithms; Animals; BT 474; Basic Science; Benchmarking; Bioluminescence; Cancer Etiology; Cessation of life; Combined Modality Therapy; Computer software; Consumption; Detection; Disease; Disease Progression; Disseminated Malignant Neoplasm; Drug Delivery Systems; Excision; Fluorescence; Goals; Histologic; Histology; Image; Imaging Techniques; Label; Laboratories; Longitudinal Studies; Lung; Malignant Neoplasms; Mammary Neoplasms; Metastatic Neoplasm to the Lung; Metastatic malignant neoplasm to brain; Methodology; Modality; Modeling; Monitor; Mus; Neoplasm Metastasis; Noise; Non-Invasive Cancer Detection; Optical Tomography; Optics; Performance; Photons; Physiological; Proteins; Provider; Radiology Specialty; Reagent; Reporter; Resolution; Signal Transduction; System; Systems Development; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Transillumination; Translating; Trastuzumab; Treatment Protocols; Validation; X-Ray Computed Tomography; anatomic imaging; angiogenesis; anticancer research; base; bioluminescence imaging; cancer cell; cancer imaging; clinically relevant; cohort; cyanine dye 5; design; detection limit; detection sensitivity; drug discovery; fluorescence imaging; fluorophore; imaging capabilities; imaging modality; imaging platform; imaging software; imaging system; improved; in vivo imaging system; industry partner; microCT; molecular imaging; multimodality; novel; novel therapeutics; optical imaging; photon-counting detector; pre-clinical; pre-clinical research; preclinical imaging; prototype; radiological imaging; reconstruction; response; serial imaging; subcutaneous; time use; tomography; treatment strategy; tumor; tumor growth; user-friendly

The lack of an efficient, rapid preclinical imaging modality for non-invasive detection and longitudinal tracking of early stage metastatic cancer in whole animals has been a significant hindrance to drug discovery studies. Current studies of novel drug delivery and metastasis treatment strategies require large cohorts of serially sacrificed animals. Optical molecular imaging offers great promise as a longitudinal imaging technique for preclinical cancer research. The unique advantage of optical imaging over radiological modalities is the capability for lifetime and spectral labelling to track multiple physiological components of disease simultaneously (multiplexing). Fluorescence lifetime contrast using time domain (TD) detection also enables the efficient removal of tissue autofluorescence, a major impediment for whole body optical imaging. We have demonstrated that lifetime contrast with time domain (TD) optical detection provides a more than 20-fold sensitivity increase over traditional continuous wave (CW) fluorescence imaging for detecting iRFP-labeled cancer cells dispersed in the mouse lung. These results demonstrate the high potential of TD imaging for monitoring metastasis in whole mice at earlier stages than currently possible. Motivated by our progress and the potential impact of the technology for preclinical cancer imaging, our goal in this academic industry partnership is to integrate time domain technology into a commercially established preclinical imaging system from PerkinElmer, a leading provider of in vivo imaging systems and reagents. MGH and PerkinElmer will partner to develop a robust prototype time domain preclinical optical tomography platform and validate the system using small animal tumor models. The system will also incorporate micro-CT imaging for anatomical co-registration and to aid the optical tomography algorithms. The system will be designed to meet performance criteria for commercial use. The proposed imaging platform will provide several new benefits to existing commercial imaging platforms from PKI, including 1) more than 20-fold improvement in sensitivity using autofluorescence removal, allowing the detection of metastasis earlier than currently possible; (2) lifetime multiplexing to visualize multiple fluorophores simultaneously in a single animal; (3) improved resolution over CW using early photon detection; (4) accurate and fast 3D fluorescence reconstructions using accelerated Monte Carlo software. These features will add to the existing capability of PerkinElmer's systems for bioluminescence, multispectral fluorescence and CT imaging, to deliver the most versatile preclinical optical imaging platform commercially available. .

缺乏有效、快速的非侵入性检测和临床前成像手段 对整个动物的早期转移性癌症的纵向追踪是一个重要的 阻碍药物发现研究。新型药物传递和转移的研究现状 治疗策略需要大量连续牺牲的动物。光学分子 作为一种纵向成像技术，成像为临床前癌症研究提供了巨大的前景。 光学成像相对于放射成像的独特优势是能够终生使用 和光谱标记，以同时跟踪疾病的多个生理成分 (多路传输)。使用时间域(TD)检测的荧光寿命对比度还使 有效地去除组织的自发荧光，这是全身光学成像的主要障碍。 我们已经证明，与时间域(TD)光学检测的寿命对比提供了 灵敏度比传统的连续波(CW)荧光提高20倍以上 用于检测散布在小鼠肺内的irrfp标记癌细胞的成像。这些结果 早期显示TD成像在监测整个小鼠转移中的高潜力 比目前可能的阶段更多。动机是我们的进步和 临床前癌症成像技术，我们在这个学术行业合作伙伴关系中的目标是 将时域技术集成到商业建立的临床前成像系统中 来自体内成像系统和试剂的领先供应商PerkinElmer。MGH和 PerkinElmer将合作开发一种强大的时域临床前光学原型 层析成像平台，并使用小动物肿瘤模型验证系统。系统将 还结合了用于解剖联合配准的Micro-CT成像，并辅助光学 层析成像算法。该系统的设计将满足以下性能标准 商业用途。拟议的成像平台将为现有的 来自PKI的商业成像平台，包括1)在以下方面提高20倍以上 使用自体荧光去除的敏感性，允许更早地检测到转移 目前可能的；(2)生命周期多路复用，以在一个 单个动物；(3)使用早期光子检测提高了CW的分辨率；(4)准确和 使用加速蒙特卡罗软件进行快速三维荧光重建。这些功能 将增加PerkinElmer系统现有的生物发光、多光谱 荧光和CT成像，提供最多功能的临床前光学成像平台 商业上可以买到的。 。