Acoustic Loudness Factor as an Experimental Parameter for Benchmarking Small Molecule Photoacoustic Probes

Authors

• Frederik Brøndsted, University of Virginia
• Julia L. McAfee, University of Virginia
• Jerimiah D. Moore, University of Virginia
• Harry R. Shield, University of Virginia
• Luca Menozzi, Duke University
• Xinqi Zhou, University of Nebraska-Lincoln
• Yuan Fang, University of Virginia
• Ruwen Yin, University of Virginia
• Junjie Yao, Duke University
• Kelsey P. Kubelick, University of Virginia
• Cliff I. Stains, University of Virginia and Virginia Drug Discovery Consortium

ORCID IDs

Menozzi https://orcid.org/0000-0001-7542-1051

Fang https://orcid.org/0000-0003-1987-0885

Yao https://orcid.org/0000-0002-2381-706X

Kubelick https://orcid.org/0000-0002-6342-2994

Stains https://orcid.org/0000-0002-3165-4539

Document Type

Article

Date of this Version

2025

Citation

Nature Communications (2025) 16: 3779

doi: 10.1038/s41467-025-59121-6

Comments

Open access

License: CC BY-NC-ND 4.0

Abstract

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.