Spatial and Spectral Mapping and Decomposition of Neural Dynamics and Organization of the Mouse Brain with Multispectral Optoacoustic Tomography

Abstract

Summary In traditional optical imaging, limited light penetration constrains high-resolution interrogation to tissue surfaces. Optoacoustic imaging combines the superb contrast of optical imaging with deep penetration of ultrasound, enabling a range of new applications. We used multispectral optoacoustic tomography (MSOT) for functional and structural neuroimaging in mice at resolution, depth, and specificity unattainable by other neuroimaging modalities. Based on multispectral readouts, we computed hemoglobin gradient and oxygen saturation changes related to processing of somatosensory signals in different structures along the entire subcortical-cortical axis. Using temporal correlation analysis and seed-based maps, we reveal the connectivity between cortical, thalamic, and sub-thalamic formations. With the same modality, high-resolution structural tomography of intact mouse brain was achieved based on endogenous contrasts, demonstrating near-perfect matches with anatomical features revealed by histology. These results extend the limits of noninvasive observations beyond the reach of standard high-resolution neuroimaging, verifying the suitability of MSOT for small-animal studies.

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 .…”

Croconaine-based nanoparticles enable efficient optoacoustic imaging of murine brain tumors

“…The multispectral optoacoustic technique MSOT allows simultaneous imaging of multiple endogenous chromophores in the brain for assessment of brain structure and function [ 7 , 51 , 64 ]. Here we extended the brain imaging abilities of MSOT by using an exogenous contrast agent that can target brain tumors and generate a strong optoacoustic signal even deep below the brain surface.…”

“…Several label-free optoacoustic imaging applications have been showcased using endogenous chromophores for contrast generation [ 4 ]. Using hemoglobin for example, optoacoustic imaging was used to visualize angiogenesis, tissue oxygenation, inflammation, and metabolic processes [ [5] , [6] , [7] , [8] , [9] ]. However, to enable significantly richer profiling of biological activities, there is a need for additional low-cost agents that are versatile and easy to synthesize or structurally modify [ 2 ].…”

Advances in Optoacoustic Neurotomography of Animal Models

“…With the added value of multispectral capabilities, it has been applied in a range of structural neuroimaging studies as well as in the comparative analysis of morphological changes associated with brain disease in intact-and open-skull murine preparations [12,13]. The majority of noninvasive structural studies capitalized on hemoglobin absorption [15,23,[32][33][34]. Using external illumination, highresolution brain cross-sections were obtained, revealing organization with exquisite anatomical detail (Figure 2A,B).…”

“…Using external illumination, highresolution brain cross-sections were obtained, revealing organization with exquisite anatomical detail (Figure 2A,B). In mice, numerous structural references in the brain were readily visualized using a transcranial approach [14,15,23,32,34]. In combination with ultrasonography in the same preparation, hybrid images were acquired and correlated with histological data [15].…”