Advancing Spectroscopic Photoacoustic Imaging for Biomedical Applications: Opportunities, Challenges, and Pathways to...

Photoacoustic imaging is an emerging imaging modality with unique features that have attracted significant interest for clinical translation. Spectroscopic photoacoustic (sPA) imaging acquires photoacoustic images at multiple wavelengths, enabling the differentiation of chromophores at greater depths than conventional optical imaging while maintaining spatial resolution comparable to ultrasound. It is a straightforward integration with ultrasound imaging that provides a powerful diagnostic platform for structural, functional, and molecular imaging. This capability makes it somewhat analogous to combined X-ray computed tomography (CT) and positron emission tomography (PET), but without ionizing radiation, offering a safer and more accessible alternative for a broader patient population. While spectroscopic photoacoustic imaging, with or without exogenous contrast agents, has shown great potential in various preclinical applications, its clinical translation faces several technical and practical challenges. These include limitations in light penetration, spectral unmixing complexities, and the need for improved image reconstruction techniques. Additionally, standardization and regulatory considerations must be addressed to facilitate widespread clinical adoption. In this review, we introduce spectroscopic photoacoustic imaging, highlighting its significant potential to address critical gaps in biomedical diagnostics. We further discuss the key technical and practical limitations hindering its clinical implementation and explore recent advancements aimed at overcoming these barriers.