Turn the heat on: High resolution fluorescence imaging via temperature modulation

打开热量：通过温度调制进行高分辨率荧光成像

• 批准号: 9070752
• 负责人: GULTEKIN GULSEN
• 金额: $ 17.94万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9070752
• 关键词: Adverse effects; Algorithms; Animal Model; Animals; Area; Binding; Blood Circulation; Body Temperature; Caliber; Categories; Clinical; Complement; Contrast Media; Diffuse; Disadvantaged; Evaluation; Event; Exploratory/Developmental Grant; FOLH1 gene; Feasibility Studies; Fluorescence; Fluorescent Dyes; Focused Ultrasound; Goals; Gold; Health; Heating; Hot Spot; Image; Imaging Techniques; Implant; LNCaP; Life; Location; Magnetic Resonance Imaging; Maps; Microbubbles; Modeling; Molecular Probes; Nature; Noise; Nude Rats; Optical Image Reconstruction; Optics; Performance; Photons; Physiologic pulse; Positioning Attribute; Process; Property; Reporting; Resolution; Role; Signal Transduction; Spottings; Surface; System; Techniques; Temperature; Testing; Thick; Three-Dimensional Imaging; Time; Tissues; Transducers; Translating; Tube; Ultrasonography; absorption; base; cancer diagnosis; clinical application; contrast enhanced; cost; fluorescence imaging; fluorophore; high risk; imaging modality; improved; in vivo; in vivo imaging; instrumentation; interest; light intensity; molecular imaging; nanoparticle; novel; optical imaging; photon-counting detector; pre-clinical; prostate cancer cell line; prototype; quantum; reconstruction; residence; response; simulation; success; theranostics; tool; treatment planning; tumor; vibration

 DESCRIPTION (provided by applicant): With the advent of fluorescence probes targeting specific cellular and subcellular events, the role of fluorescent imaging in preclinical and clinicl arena is getting progressively stronger. Fluorescence probes mainly consist of the active component, which interacts with the target, and the reporting component such as the fluorescent dye. Operating in the near-infrared spectrum in which the tissue absorption is minimum, these probes can be detected in vivo even if they are located deep. The advantages of fluorescence imaging are its high sensitivity, low-cost and contrast agents with long shelf-life However, high tissue scattering leads to poor resolution and low quantitative accuracy that hinder the progress of fluorescence imaging towards clinical applications. An intriguing solution to this problem is to use a focused ultrasound beam and tag the diffused fluorescence photons in the focal zone. By detecting and analyzing the tagged (or modulated) fluorescence photons, distribution of the fluorescence probes can be recovered with higher resolution since ultrasound can be focused into a small zone deep in tissue. However, this technique suffers from the low signal to noise ratio due to limited modulation depth in the optical signal generated by the ultrasound modulation. Our main goal in this proposal is to use focused ultrasound to improve fluorescence imaging as well but in a different way: by achieving thermal modulation in the focal zone. Utilizing recently available temperature sensitive fluorescent molecular probes, our approach is thermal outlining using focused ultrasound (TOFU) and uses this as a priori information for fluorescence imaging to attain superior resolution and excellent quantitative accuracy. The advantage of our approach is the high optical modulation depth provided by these contrast agents (up to ten-fold) with only 4K temperature increase. We have already developed a 2D prototype system and in this study we will extend it to a 3D TOFU system. Once optimized with extensive phantom studies, we will evaluate the performance of the proposed technique with small animals bearing PSMA positive orthotopic tumor models together with PSMA targeting temperature sensitive fluorescent molecular probes.

 描述（由申请人提供）：随着靶向特定细胞和亚细胞事件的荧光探针的出现，荧光成像在临床前和临床竞技场中的作用越来越强。荧光探针主要由与靶标相互作用的活性组分和荧光染料等报告组分组成。在组织吸收最小的近红外光谱中工作，这些探针即使位于深处也可以在体内检测到。荧光成像具有灵敏度高、成本低、造影剂保存期长等优点，但组织散射高导致分辨率差、定量准确性低，阻碍了荧光成像向临床应用的发展。这个问题的一个有趣的解决方案是使用聚焦超声波束并标记焦点区域中的扩散荧光光子。通过检测和分析标记的（或调制的）荧光光子，可以以更高的分辨率恢复荧光探针的分布，因为超声可以聚焦到组织深处的小区域中。然而，由于超声调制产生的光信号中的调制深度有限，该技术具有低信噪比的缺点。我们在这个提案中的主要目标是使用聚焦超声来改善荧光成像，但以不同的方式：通过在聚焦区实现热调制。利用最近可用的温度敏感的荧光分子探针，我们的方法是热概述使用聚焦超声（TOFU），并使用此作为先验信息的荧光成像，以达到上级分辨率和出色的定量精度。我们的方法的优点是由这些造影剂提供的高光学调制深度（高达十倍），温度仅增加4K。我们已经开发了一个二维原型系统，在这项研究中，我们将它扩展到一个三维TOFU系统。一旦通过广泛的体模研究进行优化，我们将使用携带PSMA阳性原位肿瘤模型的小动物以及PSMA靶向温度敏感性荧光分子探针来评估所提出的技术的性能。