Abstract

The ability to non-invasively visualize endogenous chromophores and exogenous probes and sensors across the entire rodent brain with the high spatial and temporal resolution has empowered optoacoustic imaging modalities with unprecedented capacities for interrogating the brain under physiological and diseased conditions. This has rapidly transformed optoacoustic microscopy (OAM) and multi-spectral optoacoustic tomography (MSOT) into emerging research tools to study animal models of brain diseases. In this review, we describe the principles of optoacoustic imaging and showcase recent technical advances that enable high-resolution real-time brain observations in preclinical models. In addition, advanced molecular probe designs allow for efficient visualization of pathophysiological processes playing a central role in a variety of neurodegenerative diseases, brain tumors, and stroke. We describe outstanding challenges in optoacoustic imaging methodologies and propose a future outlook.

Highlights

  • Optoacoustic imaging and tomography as a new modality in neuroscience research Advances in imaging technology have led to tremendous breakthroughs in life sciences and biomedicine

  • Cutting-edge neuroimaging tools have greatly aided in the understanding of brain organization while being instrumental in studying and treating brain disorders [1–8]

  • 2 Zurich Neuroscience Center (ZNZ), Zurich, Switzerland 3 Faculty of Medicine and Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland 4 Institute for Regenerative Medicine, Uiversity of Zurich, Zurich, Switzerland understanding the molecular pathophysiology of most brain diseases, we are still far from linking information on molecules, gene regulatory events, and signaling pathways to the changes that occur over time on the tissue and organ level in an integrative way [12]

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Summary

Introduction

Optoacoustic imaging and tomography as a new modality in neuroscience research Advances in imaging technology have led to tremendous breakthroughs in life sciences and biomedicine. OA relies on the photophonic phenomenon first described by Tainter and Bell in 1880 where intermittent light radiation is absorbed by molecules and converted into heat, leading to instantaneous thermoelastic expansion and induction of broadband pressure waves [22] It has yet taken more than a century of technological progress bringing about intense pulsed laser sources, sensitive broadband ultrasound arrays, fast digitization electronics, and efficient image reconstruction algorithms, to enable practical biomedical OA imaging systems [23, 24]. Tunable laser sources in the near-infrared range, where tissue optical absorption is reduced, are commonly employed for in vivo imaging applications, allowing for deep tissue penetration of the excitation photons In this way, distribution of tissue chromophores and photoabsorbing agents can be rendered tomographically via single transducer scanning or parallelized OA signal detection with arrayed probes accompanied by suitable image reconstruction algorithms, e.g., based on backprojection or model-based inversion approaches [25, 26]. OA techniques effectively bridge the gap between microscopic and macroscopic brain imaging realms and are uniquely endowed with high-resolution, fast, multiscale, and multiplex imaging capacities in small-animal organisms in vivo

Endogenous contrast for structural and functional imaging
MSOT probes for molecular imaging
Application in elucidating brain diseases
Endogenous contrast
Bacterial phytochrome
Multimodal imaging
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