Integrating optoacoustic microscopy with existing and emerging imaging modalities: a review

Multimodal imaging integrates complementary contrasts to improve the understanding of physiological processes and disease progression. In this review, we aim to summarize and critically assess the integration of optoacoustic microscopy (OAM) with established ultrasound-based and optical microscopy-based modalities, addressing how these hybrid systems enhance structural, functional, and molecular imaging across biomedical applications. A comprehensive literature review was conducted focusing on OAM-based multimodal microscopy platforms integrated with ultrasound microscopy and optical techniques, including optical coherence tomography, fluorescence microscopy, multiphoton microscopy, light-sheet microscopy, and Raman spectroscopy. Emerging strategies such as integration with quantitative phase imaging and advanced signal processing approaches, including the multiple signal classification algorithm, were also examined. Studies were analysed with respect to system design, image co-registration and fusion strategies, and application domains including oncology, dermatology, ophthalmology, and neuroscience. Multimodal OAM platforms demonstrated enhanced imaging performance by combining high optical contrast with improved penetration depth and functional sensitivity. These systems enabled detailed visualization of oxygenation, tumor angiogenesis, skin microarchitecture, retinal structures, and neuronal activity. Comparative analysis revealed trade-offs and synergies among modalities in terms of spatial resolution, penetration depth, frame rate, and field-of-view, highlighting the advantages of hybrid configurations over single-modality approaches. Hybrid OAM-based multimodal microscopy provides a powerful framework for comprehensive biomedical imaging. By leveraging complementary contrasts and advanced image fusion strategies, these platforms hold strong potential to advance both fundamental research and translational clinical applications.