Abstract
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.
Highlights
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
Because of the small size of nanoparticles, thermal energy generated from optical absorption diffuses out rapidly into the surrounding medium, and the intensity of photoacoustic signal is proportional to this outgoing thermal flux[11]
PNIPAM nanogels are advantageous as their volume rapidly reduces as temperature rises above their lower critical solution temperature (LCST), a phenomenon that is caused by phase transition of hydrophobic moieties of the polymer chain[15]
Summary
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. Some types of tissue produce strong endogenous background signals that can generate false positive results in contrastenhanced photoacoustic imaging To rule out these false positives, a spectral scan, that sweeps the illuminating laser light across multiple wavelengths, is often needed. Such fluorophore-based contrast agents are relatively inefficient and less thermodynamically stable than colloidal nanoparticles, leading to a lower (micro-molar) imaging sensitivity Most of these agents require an optical stimulus in a short wavelength (o800 nm) and none can currently operate in the wavelength range within the second near infrared window of tissue (1–1.4 mm), a wavelength range in which tissue generates the weakest background photoacoustic signals. We hypothesize that a nanoparticle cluster, in which the inter-particle separation can be varied in a controlled manner, can be an efficient stimuliresponsive probe for dynamic contrast-enhanced photoacoustic imaging
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