Acoustic loudness factor as an experimental parameter for benchmarking small molecule photoacoustic probes

Photoacoustic imaging (PAI) is an emerging biomedical imaging modality with promise as a point-of-care diagnostic. This imaging modality relies on optical excitation of an absorber followed by production of ultrasound through the photoacoustic effect, resulting in high spatial resolution with imaging depths in the centimeter range. Herein, we disclose the discovery of the first benchmarking parameter for small molecule dye performance in PAI, which we term the acoustic loudness factor (ALF). ALF can predict dye performance in PAI without the need for access to photoacoustic instrumentation and can be used to guide the systematic evaluation of design strategies to enhance photoacoustic signal. Lastly, we demonstrate that enhancements in ALF can be translated to in vivo PAI. Akin to the use of fluorescence brightness in fluorophore design and evaluation for fluorescence imaging, we anticipate that ALF will guide the design and evaluation of improved probes for PAI.