Dual-wavelength hybrid optoacoustic-ultrasound biomicroscopy for functional imaging of large-scale cerebral vascular networks.

A critical link exists between pathological changes of cerebral vasculature and diseases affecting brain function. Microscopic techniques have played an indispensable role in the study of neurovascular anatomy and functions. Yet, investigations are often hindered by suboptimal trade-offs between the spatiotemporal resolution, field-of-view (FOV) and type of contrast offered by the existing optical microscopy techniques. We present a hybrid dual-wavelength optoacoustic (OA) biomicroscope capable of rapid transcranial visualization of large-scale cerebral vascular networks. The system offers 3-dimensional views of the morphology and oxygenation status of the cerebral vasculature with single capillary resolution and a FOV exceeding 6 × 8 mm2 , thus covering the entire cortical vasculature in mice. The large-scale OA imaging capacity is complemented by simultaneously acquired pulse-echo ultrasound (US) biomicroscopy scans of the mouse skull. The new approach holds great potential to provide better insights into cerebrovascular function and facilitate efficient studies into neurological and vascular abnormalities of the brain.

Virtual craniotomy for high-resolution optoacoustic brain microscopy.

Ultrasound-mediated transcranial images of the brain often suffer from acoustic distortions produced by the skull bone. In high-resolution optoacoustic microscopy, the skull-induced acoustic aberrations are known to impair image resolution and contrast, further skewing the location and intensity of the different absorbing structures. We present a virtual craniotomy deconvolution algorithm based on an ultrasound wave propagation model that corrects for the skull-induced distortions in optically-resolved optoacoustic transcranial microscopy data. The method takes advantage of the geometrical and spectral information of a pulse-echo ultrasound image of the skull simultaneously acquired by our multimodal imaging system. Transcranial mouse brain imaging experiments confirmed the ability to accurately account for the signal amplitude decay, temporal delay and pulse broadening introduced by the rodent's skull. Our study is the first to demonstrate skull-corrected transcranial optoacoustic imaging in vivo.