Near-infrared time-domain ultrasound-switchable fluorescence imaging

Shuai Yu, Yuan Liu, Jayanth Kandukuri, Tingfeng Yao, Baohong Yuan
2017 Optics in the Life Sciences Congress   unpublished
Fluorescence imaging in centimeter-deep tissues with high resolution is highly desirable for many biomedical applications. Recently, we have developed a new imaging modality, ultrasound-switchable fluorescence (USF) imaging, for achieving this goal. In our previous work, we successfully achieved USF imaging with several types of USF contrast agents and imaging systems. In this study, we introduced a new USF imaging system: an intensified charge-coupled device (ICCD) camera-based, time-domain
more » ... sed, time-domain USF imaging system. We demonstrated the principle of time-domain USF imaging by using two USF contrast agents. With a series of USF imaging experiments, we demonstrated the tradeoffs among different experimental parameters (i.e., data acquisition time, including CCD camera recording time and intensifier gate delay; focused ultrasound (FU) power; and imaging depth) and the image qualities (i.e., signal-to-noise ratio, spatial resolution, and temporal resolution). In this study, we also discussed several imaging strategies for achieving a high-quality USF image via this time-domain system. Fluorescence imaging in deep biological tissue is extremely desirable because it reveals the tissue's structural, functional, and molecular information with high-sensitivity, non-ionizing radiation and good penetration 1-5 . Compared with other imaging modalities such as x-ray, ultrasound, magnetic resonance imaging (MRI), and positron-emission tomography (PET), fluorescence imaging has many unique advantages. One outstanding advantage is its multicolor imaging via multiple fluorophores that thus enables fluorophore-based biomarkers to reveal cellular-level or molecular-level biological interactions 6,7 . Unfortunately, fluorescence imaging suffers from poor spatial resolution (a few millimeters) in opaque biological tissue as a result of high scattering 8 . As a result, fluorescence imaging cannot resolve much interesting microscopic information such as microcirculation, angiogenesis, and cancer metastasis 8-10 in centimeter-deep tissues. Over the past few years, several technologies have been proposed and developed to overcome this limitation. One technology is to focus excitation light in deep tissue by focused ultrasound (FU), so called time-reversed ultrasonically encoded optical focusing 11-16 . Another technology is to confine fluorescence emission by focused ultrasound, so called ultrasound modulated or switchable fluorescence 17-42 . The former applies to any fluorophore excitation but requires a complicated imaging system. The latter requires a relatively simple system but demands unique contrast agents. Among them, we have recently developed a technique that belongs to the latter category: ultrasound switchable fluorescence (USF) imaging 17, 18, [23] [24] [25] [26] [27] [28] [29] 42 . This technique adopts thermal-sensitive fluorescence contrast agents that can be switched on/off via a FU beam 17, 18, [23] [24] [25] [26] . Fluorophores are quenched due to an initial polar microenvironment in the contrast agents so that they remain in the "off " state when no ultrasound is applied. The fluorophores are "switched-on" when the FU beam is applied. This is because that the tissue temperature is slightly raised beyond a temperature threshold (T th ) of the contrast agent, which changes the fluorophores' microenvironment from polar to nonpolar, significantly increasing the fluorophores' emission efficiency. When the excitation light is on, the emitted fluorescence is detected by the USF imaging system. By scanning the FU transducer, the USF image provides the distribution of the contrast agents in deep tissues with a high spatial resolution (down to hundreds of microns, depending on various experimental parameters). USF has a similar spatial resolution to other deep-tissue optical imaging technologies developed in the recent years, such as photoacoustic tomography 43,44 , time-reversed ultrasonically encoded optical focusing 11-16 , and ultrasound-modulated fluorescence 21,32,33 . However, USF has many unique features and here we presented a few
doi:10.1364/omp.2017.omm2d.2 fatcat:pxmvox2hlrecfotg6bgwerkgw4