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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

基本信息

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
项目类别：
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

项目摘要

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.