Noninvasive measurement of local temperature using ultrasound-switchable fluorescence

Measuring the local background temperature in diseased and inflamed tissues is highly desirable, especially in a non-invasive way. In this work, ultrasound-switchable fluorescence (USF) technique was utilized to estimate the local background temperature for the first time by analyzing the temperature dependence of fluorescence emission from USF contrast agents induced by a focused ultrasound (FU) beam. First, temperature-sensitive USF agents with distinct temperature switching-on thresholds were synthesized, and their thermal switching characteristics were quantified using an independent spectrometer system. Second, the USF contrast agent suspension was injected into a microtube that was embedded into a phantom and the dynamic USF signal was acquired using a camera-based USF system. The differential profile of the measured dynamic USF signal was computed and compared with the thermal switching characteristics. This allowed for the calculation of the local background temperature of the sample in the FU focal volume based on the estimation of heating speed. An infrared (IR) camera was used to acquire the surface temperature of the sample and further compare it with the USF system. The results showed that the difference between the temperatures acquired from the USF thermometry and the IR thermography was 0.64 ± 0.43 °C when operating at the physiological temperature range from 35.27 to 39.31 °C. These results indicated the potential use of the USF system for measuring the local temperature in diseased tissues non-invasively. The designed USF-based thermometry shows a broad application prospect in high spatial resolution temperature imaging with a tunable measurement range in deep tissue.