Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators

Molecular photoacoustic imaging has shown great potential in medical applications; its sensitivity is normally in pico-to-micro-molar range, dependent on exogenous imaging agents. However, tissue can produce strong background signals, which mask the signals from the imaging agents, resulting in orders of magnitude sensitivity reduction. As such, an elaborate spectral scan is often required to spectrally un-mix the unwanted background signals. Here we show a new single-wavelength photoacoustic dynamic contrast-enhanced imaging technique by employing a stimuli-responsive contrast agent. Our technique can eliminate intrinsic background noises without significant hardware or computational resources. We show that this new contrast agent can generate up to 30 times stronger photoacoustic signals than the concentration-matched inorganic nanoparticle counterparts. By dynamically modulating signals from the contrast agents with an external near-infrared optical stimulus, we can further suppress the background signals leading to an additional increase of more than five-fold in imaging contrast in vivo.