Broadband Model-Based Optoacoustic Mesoscopy Enables Deep-Tissue Imaging beyond the Acoustic Diffraction Limit

Optoacoustic mesoscopy (OAM) retrieves anatomical and functional contrast in vivo at depths not resolvable with optical microscopy. Recent progress on reconstruction algorithms have further advanced its imaging performance to provide high lateral resolution ultimately limited by acoustic diffraction. In this work, a new broadband model-based OAM (MB-OAM) framework efficiently exploiting scanning symmetries for an enhanced performance is presented. By capitalizing on the large detection bandwidth of a spherical polyvinylidene difluoride film while accurately accounting for its spatial impulse response, the new approach significantly outperforms standard OAM implementations in terms of contrast and resolution, as validated by functional in vivo experiments in mice and human volunteers. Furthermore, L1-norm regularization enables resolving structures separated by less than the theoretical diffraction-limited resolution. This unique label-free angiographic performance demonstrates the general applicability of MB-OAM as a super-resolution deep-tissue imaging method capable of breaking through the limits imposed by acoustic diffraction.

Time-domain model for OAM. a) Raster-scan image acquisition protocol. b) Schematic representation of the scanning symmetries. The OA signals generated at all voxels labeled with blue circles for the indicated transducer position are equivalent. Signals are preserved if the transducer and voxels are shifted by the same distance (dashed lines). c) Photograph of the sensing area of transducer (left), and a representation of the OA model based on discretizing transducer surface into sub-elements (right). The OA signals corresponding to a given voxel and all surface elements are superimposed to estimate the collected time-resolved signal for that voxel. d) Cross-sectional view of the amplitude spectral density of the modeled time-resolved signals for three different frequencies along with amplitude of these signals in the time domain. FWHM values are indicated. e) OAM images reconstructed by superimposing the acquired signals (left), with the SAFT method (middle) and with the MB-L2 method (right).

Weiye Li, Urs A. T. Hofmann, Johannes Rebling, Quanyu Zhou, Zhenyue Chen, Ali Ozbek, Yuxiang Gong, Pavel Subochev, Daniel Razansky, Xosé Luís Deán-Ben. Broadband Model-Based Optoacoustic Mesoscopy Enables Deep-Tissue Imaging beyond the Acoustic Diffraction Limit.

Laser Photonics Rev.2022,16, 2100381

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