NEUROIMAGING/PHOTOACOUSTICS: Photoacoustics enables high-res functional connectivity imaging of the mouse brain

Using optical excitation and acoustic detection, Washington University researchers have developed a functional connectivity photoacoustic tomography (fcPAT) system, which, for the first time, allows noninvasive imaging of resting-state functional connectivity (RSFC) in the mouse brain, with a large field of view and a high spatial resolution.1 Research associate Mohammad Avanaki, Ph.D., describes RSFC as one of the most exciting discoveries in neuroimaging: It aims to identify low-frequency, spontaneous cerebral hemodynamic fluctuations, which are highly correlated with the local neuronal activity.2,3 By analyzing these fluctuations, researchers found that strong correlations exist inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions.4 It was also found that the magnitude of the correlation is a strong indication of the healthiness of the brain.

Functional connectivity maps in a mouse brain acquired noninvasively by fcPAT depict correlation of the eight main functional regions (a), the four subregions of the somatosensory cortex (b), and the three subregions of the visual cortex (c). The white circles indicate seed regions: S1HL, primary somatosensory cortex – hindlimb region; S1FL, primary somatosensory – forelimb region; S1H, primary somatosensory – head region; S1BF, primary somatosensory – barrel field; V1, primary visual cortex; V2M, secondary visual cortex – medial region; and V2L, secondary visual cortex – lateral region
Functional connectivity maps in a mouse brain acquired noninvasively by fcPAT depict correlation of the eight main functional regions (a), the four subregions of the somatosensory cortex (b), and the three subregions of the visual cortex (c). The white circles indicate seed regions: S1HL, primary somatosensory cortex – hindlimb region; S1FL, primary somatosensory – forelimb region; S1H, primary somatosensory – head region; S1BF, primary somatosensory – barrel field; V1, primary visual cortex; V2M, secondary visual cortex – medial region; and V2L, secondary visual cortex – lateral region.

While extensive studies have been performed on human brain, none of the existing RSFC imaging modalities can be used in mouse, a species with the widest variety of neural disease models. For instance, functional connectivity magnetic resonance imaging (fcMRI) lacks sufficient signal-to-noise ratio (SNR) for functional imaging in mice,5 while optical intrinsic signal imaging (fcOIS) has limited spatial resolution and can image only through exposed skull, which increases the complexity of longitudinal imaging.6

The fcPAT approach addresses these challenges. With acoustic detection of optical absorption, fcPAT allows high-resolution imaging of cerebral hemodynamics through intact scalp. As photoacoustic signals originate solely from optical absorbers (hemoglobin), fcPAT is background-free and thus has a high SNR. As described in the Proceedings of the National Academy of Sciences, Avanaki et al. used fcPAT to observe bilateral correlations in eight functional regions, including the olfactory bulb, limbic, parietal, somatosensory, retrosplenial, visual, motor, and temporal regions, as well as in several subregions in the mouse brain.6 Compared with other neural imaging modalities, fcPAT allows simultaneous acquisition of vascular images, which are naturally co-registrated with the RSFC image, allowing precise localization of the functional activities.

1. M. R. N. Avanaki et al., Proc. Nat. Acad. Sci., 111, 1, 21–26 (2014).

2. B. Biswal, F. Z. Yetkin, V. M. Haughton, and J. S. Hyde, Magnet. Reson. Med., 34, 4, 537–541 (1995).

3. B. R. White et al., PLoS One, 6, 1, e16322 (2011).

4. M. D. Fox and M.E. Raichle, Nature Rev. Neurosci., 8, 9, 700–711 (2007).

5. J. Steinbrink et al., Magnet. Reson. Imaging, 24, 4, 495–505 (2006).

6. A. W. Bero et al., J. Neurosci., 32, 13, 4334–4340 (2012).

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