Advances in Optoacoustic Neurotomography of Animal Models

Abstract

Unlike traditional optical methods, optoacoustic imaging is less sensitive to scattering of ballistic photons, so it is capable of high-resolution interrogation at a greater depth. By integrating video-rate visualization with multiplexing and sensing a range of endogenous and exogenous chromophores, optoacoustic imaging has matured into a versatile noninvasive investigation modality with rapidly expanding use in biomedical research. We review the principal features of the technology and discuss recent advances it has enabled in structural, functional, and molecular neuroimaging in small-animal models. In extending the boundaries of noninvasive observation beyond the reach of customary photonic methods, the latest developments in optoacoustics have substantially advanced neuroimaging inquiry, with promising implications for basic and translational studies. Surpassing Diffraction Barriers of Optical ImagingElucidating the fundamental relationship between the structure and function of living organisms is one of the principal objectives of contemporary bioscience. Historically, in biological and medical studies, structure was viewed and interrogated independently from function, with attempts at relating them limited to wishful thinking or speculative conjectures [1,2]. Since the times of Leeuwenhoek, light microscopy has been the main workhorse of structural interrogation, facilitating biological observation via steady magnification and meticulous description of organizational details. Two key limitations of light microscopy, however, imposed major obstacles on the relation of structural data to the functions of living systems [3,4]. First, high-resolution imaging of biological specimens typically came with fixation: that is, with a death sentence. Second, no matter how advanced the optical imaging tools are, explicit observations have always been constrained to the surface of the specimen, due to the scattering of ballistic photons in deep tissue, with detrimental effects on image formation. In optical imaging, the depth limit is set by the mean propagation distance for a photon before directionality loss, a feature termed as the transport mean free path (TMFP) (see Glossary), which in biological specimens is 1 mm [3,5]. No existing high-resolution optical imaging modality can penetrate beyond this barrier, where the vast majority of biological processes unfold.Optoacoustic (photoacoustic) imaging is an emerging hybrid interrogation modality. Through the combined effects of the optical contrast mechanism and acoustic resolution, optoacoustic imaging surpasses the diffraction barrier, penetrating deeper into the specimen [6,7]. It capitalizes on the photoacoustic effect induced by the irradiation of an absorber with a short (1-100 ns) laser pulse at 5-50 kHz, which on excitation converts the energy of photons into heat, causing a fast local temperature rise. The pressure fronts induced by the resultant thermoelastic expansion propagate as ultrasound (US) waves, which can be detected by broadband transducers (in the 1...

Monitoring of Stimulus Evoked Murine Somatosensory Cortex Hemodynamic Activity With Volumetric Multi-Spectral Optoacoustic Tomography

“…Multi-spectral optoacoustic tomography (MSOT) has recently emerged as a powerful approach for studying brain activity in rodents (Ovsepian et al, 2019b). The endogenous contrast provided by the optical absorption of blood enables mapping multiple hemodynamic parameters (Hu and Wang, 2010;Li et al, 2010;Gottschalk et al, 2015Gottschalk et al, , 2017Yao et al, 2015), while the penetration depth and resolution are comparable to those achieved with fUS.…”

Optoacoustic brain stimulation at submillimeter spatial precision

“…Using endogenous, as well as exogenous absorbers, optoacoustic tomography, and microscopy have found broad biomedical applications 21,22 . More specifically, optoacoustic tomography has allowed imaging of brain structures, as well as function in a non-invasive manner [23][24][25][26] . Beyond imaging, recent advances in developing optoacoustic materials have enabled highly efficient optoacoustic conversion 27 .…”

Transcranial photoacoustic characterization of neurovascular physiology during early-stage photothrombotic stroke in neonatal piglets in vivo

“…Therefore, the ability to diagnose a focal stroke within a few hours after birth could have a major impact by enabling early enrollment and stratification in clinical trials for early treatments. Hence, noninvasive PA imaging, by differentiating focal stroke from global hypoxia-ischemia, has great potential for advancing clinical trials of neonatal stroke, along with promising technological progresses [47,48].…”