Preclinical Time domain Fluorescence Tomography Platform

临床前时域荧光断层扫描平台

• 批准号: 10322401
• 负责人: Anand T.N. Kumar
• 金额: $ 40.49万
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10322401
• 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; serial imaging; subcutaneous; time use; tomography; treatment response; 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、快速的临床前成像模式用于非侵入性检测， 在整个动物中对早期转移性癌症的纵向跟踪已经是一个重要的研究。 药物发现研究的障碍。新型药物载体与转移的研究现状 治疗策略需要大量连续处死的动物。光学分子 成像作为临床前癌症研究的纵向成像技术提供了巨大的希望。 光学成像相对于放射学方式的独特优势是能够终身 和光谱标记来同时跟踪疾病的多个生理成分 （多路复用）。使用时域（TD）检测的荧光寿命对比度也使得能够实现荧光寿命的测量。 有效去除组织自体荧光，这是全身光学成像的主要障碍。 我们已经证明，使用时域（TD）光学检测的寿命对比度提供了一个 灵敏度比传统连续波（CW）荧光提高20倍以上 用于检测分散在小鼠肺中的iRFP标记的癌细胞的成像。这些结果 证明了TD成像在早期监测整个小鼠中的转移的高潜力。 比目前可能的。由于我们的进展和 临床前癌症成像技术，我们在这个学术行业合作伙伴关系的目标是， 将时域技术集成到商业上建立临床前成像系统中 来自PerkinElmer，体内成像系统和试剂的领先供应商。MGH和 珀金埃尔默将合作开发一个强大的原型时域临床前光学 该系统可以在断层扫描平台上运行，并使用小动物肿瘤模型验证该系统。系统将 还包括用于解剖配准的微CT成像， 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。所提出的成像平台将为现有的成像系统提供几个新的好处。 来自PKI的商业成像平台，包括1）20倍以上的改进 灵敏度使用自体荧光去除，允许检测转移早于 目前可能的;（2）寿命复用，以同时在一个 单个动物;（3）使用早期光子检测提高CW分辨率;（4）准确和 快速三维荧光重建使用加速蒙特卡罗软件。这些特征 将增加珀金埃尔默系统的现有能力，用于生物发光，多光谱， 荧光和CT成像，提供最通用的临床前光学成像平台 市售。 .

项目成果

Tomographic fluorescence lifetime multiplexing in the spatial frequency domain.

空间频域中的层析荧光寿命复用。

• DOI: 10.1364/optica.5.000624
• 发表时间: 2018
• 期刊: Optica
• 影响因子: 10.4
• 作者: Kumar,AnandTN;Hou,StevenS;Rice,WilliamL
• 通讯作者: Rice,WilliamL

The Resolution Matrix in Tomographic Multiplexing: Optimization of Inter-Parameter Cross-Talk, Relative Quantitation, and Localization.

层析成像多重分析中的分辨率矩阵：参数间串扰、相对定量和定位的优化。

• DOI: 10.1109/tbme.2018.2889043
• 发表时间: 2019
• 期刊: IEEE transactions on bio-medical engineering
• 作者: Hou,StevenS;Bacskai,BrianJ;Kumar,AnandTN
• 通讯作者: Kumar,AnandTN

Tomographic phosphorescence lifetime multiplexing.

• DOI: 10.1364/ol.43.003104
• 发表时间: 2018-07-01
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: Kumar ATN;Hou SS
• 通讯作者: Hou SS

In vivo quantification of programmed death-ligand-1 expression heterogeneity in tumors using fluorescence lifetime imaging.

使用荧光寿命成像对肿瘤中程序性死亡配体 1 表达异质性进行体内定量。

• DOI: 10.21203/rs.3.rs-3222037/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Pal,Rahul;K,Murali;Matsui,Aya;Kang,Homan;Morita,Satoru;Taniguchi,Hajime;Kobayashi,Tatsuya;Morita,Atsuyo;Choi,HakSoo;Duda,DanG;Kumar,AnandTN
• 通讯作者: Kumar,AnandTN

Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice.

• DOI: 10.1038/s41551-023-01003-7
• 发表时间: 2023-03
• 期刊: Nature biomedical engineering
• 影响因子: 28.1
• 作者: Hou SS;Yang J;Lee JH;Kwon Y;Calvo-Rodriguez M;Bao K;Ahn S;Kashiwagi S;Kumar ATN;Bacskai BJ;Choi HS
• 通讯作者: Choi HS