High-resolution deep functional imaging of the whole mouse brain by photoacoustic computed tomography in vivo

Abstract

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a PACT system equipped with a high frequency linear transducer array for mapping the microvascular network of a whole mouse brain with the skull intact and studying its hemodynamic activities. The linear array was scanned in the coronal plane to collect data from different angles, and full-view images were synthesized from the limited-view images in which vessels were only partially revealed. We investigated spontaneous neural activities in the deep brain by monitoring the concentration of hemoglobin in the blood vessels and observed strong interhemispherical correlations between several chosen functional regions, both in the cortical layer and in the deep regions. We also studied neural activities during an epileptic seizure and observed the epileptic wave spreading around the injection site and the wave propagating in the opposite hemisphere.

Keywords: Photoacoustic computed tomography; deep mouse brain; functional imaging.

Fig. 1

Schematic setup of linear array PACT for mouse brain imaging.

Fig. 2

Coronal plane PACT imaging of a mouse brain through the intact skull (Bregma −1.0 mm). (a-e) Limited-view planar images reconstructed at view angles of –76, –36, 0, 36 and 76 degrees, respectively. Each of these images was averaged over 200 acquisitions. (f) Full-view planar image combined from the 39 limited-view images. The scale bar is 2 mm.

Fig. 3

Functional connectivity in a mouse brain acquired by a linear-array PACT system. (a-d) The correlation maps calculated at four representative functional regions (black circles) are overlaid onto the anatomic image that was synthesized from multiple limited-view images (Bregma −1.0 mm). The scale bar is 2 mm. S1HL, somatosensory 1, hindlimb region; HIP, hippocampal region; TH, thalamus; RHP, retrohippocampal region. (e) Time series of the filtered PA signals of a pair of correlated regions as marked in (a). The red and blue curves are corresponding to the points marked in white and black circles, respectively. Amplitudes are normalized to the maximum.

Fig. 4

Epileptiform activities of a mouse brain during a seizure, as imaged by PACT. The fractional changes in the PA amplitude at different times after the injection of 4-aminopyridine solution are superimposed on the anatomic image (Bregma –1.0 mm). The scale bar is 2 mm, and the arrow indicates the injection site.