Detection of cancer at its earliest stages requires development of low-background, clinically relevant imaging modalities. We have utilized optically modulatable dyes inside silica nanoparticles as novel modulatable photoacoustic contrast agents to provide truly background-free photoacoustic images in near real-time. Because photoacoustic (PA) imaging uses photogenerated and minimally scattered acoustic waves for image reconstruction, PA imaging enables optical contrast deep within tissue. However, PA imaging is typically plagued by large background signals from endogenous chromophores, thus we utilize a two-pulse PA excitation scheme to directly and selectively recover only our contrast agent signals without any background signals. Contrast agents in several spectral regions have been utilized and are being used in vivo to target sentinel lymph nodes. Contrast agents with high photogenerated dark state yields produce the necessary nonlinearity in signal to produce excellent modulated PA contrast. Initially, correlating fluorescence and PA modulation studies, we have demonstrated excellent sensitivity using Xanthene dyes (Rose Bengal, Eosin Y) embedded in silica nanoparticles. The different dark state lifetimes provide the opportunity for PA lifetime imaging to separate contrast agents that are excited by the same excitation pulse. This additional dimension in PA imaging enables simultaneous discrimination of multiple targeted pathologies, while monitoring biological markers <i>in vivo,</i> in real-time. Compared with spectroscopic PA – the standard for background signal elimination, SAPhIRe (Synchronously Amplified Photoacoustic Image Recovery) offers improved background suppression with far fewer acquisitions, thereby reducing motion artifacts and increasing frame rate.

Background-free modulated photoacoustic imaging

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.