Ultrasound-mediation of self-illuminating reporters improves imaging resolution in optically scattering media

Abstract

In vivo imaging of self-illuminating bio-and chemiluminescent reporters is used to observe the physiology of small animals. However, strong light scattering by biological tissues results in poor spatial resolution of the optical imaging, which also degrades the quantitative accuracy. To overcome this challenging problem, focused ultrasound is used to modulate the light from the reporter at the ultrasound frequency. This produces an ultrasound switchable light ‘beacon’ that reduces the influence of light scattering in order to improve spatial resolution. The experimental results demonstrate that apart from light modulation at the ultrasound frequency (AC signal at 3.5 MHz), ultrasound also increases the DC intensity of the reporters. This is shown to be due to a temperature rise caused by insonification that was minimized to be within acceptable mammalian tissue safety thresholds by adjusting the duty cycle of the ultrasound. Line scans of bio-and chemiluminescent objects embedded within a scattering medium were obtained using ultrasound modulated (AC) and ultrasound enhanced (DC) signals. Lateral resolution is improved by a factor of 12 and 7 respectively, as compared to conventional CCD imaging. Two chemiluminescent sources separated by ~10 mm at ~20 mm deep inside a 50 mm thick chicken breast have been successfully resolved with an average signal-to-noise ratio of approximately 8-10 dB.

Recent advances in ultrasound-controlled fluorescence technology for deep tissue optical imaging

“…A combined light-pulse-delay and photon counting method can also be applied to obtain the ultrasound-controlled fluorescence images using a N-{2-[(7- N , N -dimethylaminosuflonyl)-2,1, 3-benzoxadiazol-4-yl] (methyl)amino} ethyl- N -methylacrylamide (DBD-AA) labeled poly N -isopropylacrylamide probe [ 13 ]. Meanwhile, scientists have explored the ultrasound-mediation of fluorescence imaging based on the bioluminescence and chemiluminescence mechanisms [ 14 ], and time-reversed ultrasonically encoded optical focusing that transmitting light into any defined location [ 15 ]. Nevertheless, the limited photons in the detected area restrict the acceptable sensitivity of NIR fluorescence imaging.…”

In vivo ultrasound-switchable fluorescence imaging

“…To address these challenges, several technologies have been or are being investigated, such as ultrasound-modulated fluorescence [10][11] or luminescence 12 , ultrasound-induced temperature-controlled fluorescence [13][14][15] or luminescence 16 , and time-reversed ultrasonically encoded optical focusing [17][18][19][20][21] . These technologies have been shown to be able to achieve high acoustic resolution and retain fluorescence (or luminescence) contrast in deep scattering media.…”