Extended short wave infrared three-dimensional fluorescence and X-ray CT molecular tomography (SWIR FMT)

扩展短波红外三维荧光和 X 射线 CT 分子断层扫描 (SWIR FMT)

• 批准号: 416375901
• 负责人: Professor Dr. Vasilis Ntziachristos
• 金额: --
• 依托单位: Lehrstuhl für Biologische Bildgebung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/416375901?language=en
• 关键词: Extended; short; wave; infrared; three

Near-infrared (NIR) fluorescence imaging has been considered over the past 2 decades for biological and clinical imaging. In contrast to visible light, NIR light can penetrate tissues through several centimeters due to reduced light attenuation. To achieve quantification and three-dimensional fluorescence imaging in-vivo we have developed Fluorescence Molecular Tomography (FMT) and demonstrated readings of biological function in animals and humans using different classes of fluorescent agents. We have further developed hybrid FMT-XCT, achieved by incorporation of an X-ray Computed Tomography (XCT) system onto the same gantry as the FMT system. We showed that the hybrid system not only adds anatomical references to the fluorescence images but also achieves more accurate FMT reconstructions than stand-alone FMT, by feeding XCT information into the FMT inversion code for attenuation correction and improved regularization of the inverse problem. FMT-XCT has been employed in recent years for high resolution three-dimensional imaging of bone remodeling, lung cancer, quantification of asthmatic inflammation or characterization of rheumatoid arthritis in animals and humans. The current application proposes a next grand step into the development of the FMT technology, which is expected to bring a marked improvement in the resolution achieved, by adapting operation of the system to the so called short wave infrared window (SWIR, 1000-1700nm). The advantage of SWIR over NIR-I is that of significant reduced photon scattering, which can lead to significant improvements in the resolution achieved. While fluorescence imaging in the SWIR area has been impeded so far by the lack of sensitive cameras and biocompatible fluorescent probes suitable for this window, the recent development of promising contrast agents and camera technology has rendered SWIR region as very promising for imaging applications. Therefore, the aim of this proposal is to translate our existing FMT-XCT system into the world’s first SWIR FMT system. Two critical adaptations are required. First we must utilize Indium gallium arsenide (InGaAs) cameras, over the limited spectral response NIR-I FMT cameras used today. Second, it is important to modify the forward problem employed in image reconstruction, so that it accurately models photon propagation at reduced scatter. Then, we will validate the new SWIR FMT system by assessing its ability to pinpoint small tumors with high spatial resolution or to visualize small amounts of fluorescence-labelled cells in vivo. We expect that SWIR FMT will define a new standard in fluorescence imaging achieving resolution and accuracy that was never before available to diffuse, three-dimensional fluorescence images of tissues.

近红外（NIR）荧光成像在过去的20年中一直被认为是生物和临床成像。与可见光相比，由于减少的光衰减，NIR光可以穿透组织几厘米。为了实现体内定量和三维荧光成像，我们开发了荧光分子断层扫描（FMT），并使用不同类别的荧光剂在动物和人类中展示了生物功能的读数。我们进一步开发了混合FMT-XCT，通过将X射线计算机断层扫描（XCT）系统与FMT系统合并到同一台架上来实现。我们表明，混合系统不仅为荧光图像添加了解剖参考，而且通过将XCT信息输入到FMT反演代码中进行衰减校正和改进逆问题的正则化，实现了比独立FMT更准确的FMT重建。近年来，FMT-XCT已被用于动物和人类中骨重建、肺癌、哮喘炎症的定量或类风湿性关节炎的表征的高分辨率三维成像。本申请提出了FMT技术发展的下一个重大步骤，通过使系统的操作适应于所谓的短波红外窗口（SWIR，1000 - 1700nm），预计FMT技术将带来所实现的分辨率的显著改善。SWIR相对于NIR-I的优势在于显著减少了光子散射，这可以显著提高所实现的分辨率。虽然荧光成像在SWIR领域一直阻碍到目前为止，缺乏敏感的相机和生物相容性的荧光探针适合这个窗口，最近的发展有前途的造影剂和相机技术呈现SWIR区域作为非常有前途的成像应用。因此，本提案的目的是将我们现有的FMT-XCT系统转化为世界上第一个SWIR FMT系统。需要两个关键的调整。首先，我们必须利用砷化铟镓（InGaAs）相机，超过目前使用的有限光谱响应NIR-I FMT相机。其次，重要的是修改图像重建中采用的前向问题，以便其在减少散射的情况下准确地模拟光子传播。然后，我们将通过评估其以高空间分辨率精确定位小肿瘤或在体内可视化少量荧光标记细胞的能力来验证新的SWIR FMT系统。我们预计，SWIR FMT将定义一个新的标准，在荧光成像实现分辨率和准确性，这是以前从未提供扩散，三维荧光图像的组织。