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(申请人提供)：随着针对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领域的作用越来越强。荧光探针主要由与靶标相互作用的活性成分和荧光染料等报告成分组成。这些探针工作在组织吸收最小的近红外光谱中，即使它们位于深处，也可以在体内检测到。荧光成像具有灵敏度高、成本低、造影剂保质期长等优点，但组织的高散射导致分辨率低、定量精度低，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的超声束，并在焦点区域标记扩散的荧光光子。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，因为超声波可以聚焦到组织深处的小区域。然而，由于超声调制产生的光信号的调制深度有限，该技术存在信噪比低的问题。我们在这项建议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：通过在焦点区域实现热调制。利用最近可用的温度敏感的荧光分子探针，我们的方法是使用聚焦超声(豆腐)进行热轮廓，并将其作为荧光成像的先验信息，以获得卓越的分辨率和出色的定量准确性。我们的方法的优点是这些造影剂提供了高的光学调制深度(高达10倍)，而温度只增加了4K。我们已经开发了一个2D原型系统，在这项研究中，我们将把它扩展到3D豆腐系统。一旦通过广泛的模体研究进行优化，我们将评估建议的技术在携带PSMA阳性原位肿瘤模型的小动物以及PSMA靶向温度敏感荧光分子探针的情况下的性能。