A Platform for Brain-wide Volumetric Functional Ultrasound Imaging and Analysis of Circuit Dynamics in Awake Mice

Brunner, Clément; Grillet, Micheline; Sans-Dublanc, Arnau; Farrow, Karl; Lambert, Théo; Macé, Émilie; Montaldo, Gabriel; Urban, Alan

doi:10.1016/j.neuron.2020.09.020

Cited by 76 publications

(95 citation statements)

References 64 publications

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“…Although recent promising advances in the development of 2D Matrix arrays or Row Columns arrays have been proposed for full 3D functional ultrasound imaging [34,35,36], their sensitivity remains limited which still precludes transcranial imaging in mice. The proposed approach still remains valid for volumetric imaging even if the need for perfectly positioning the probe prior to the acquisition is reduced as there remain more possibilities to register volumes in post-processing.…”

Section: Discussionmentioning

confidence: 99%

Fully-automatic ultrasound-based neuro-navigation : The functional ultrasound brain GPS

Nouhoum

Ferrier²,

Osmanski³

et al. 2021

Preprint

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Recent advances in ultrasound imaging triggered by ultrafast plane waves transmission have rendered functional ultrasound (fUS) imaging a valuable neuroimaging modality capable of mapping cerebral vascular networks, but also to indirectly capture neuronal activity with high sensitivity thanks to the neurovascular coupling. However, the expansion of fUS imaging is still limited by the difficulty to identify cerebral structures during experiments based solely on the Doppler images and the shape of the vessels. In order to tackle this challenge, this study introduces the vascular brain positioning system (BPS), a GPS of the brain. The BPS is a whole-brain neuro-navigation system based on the on-the-fly automatic alignment of ultrafast ultrasensitive transcranial Power Doppler volumic images to common templates such as the Allen mouse brain Common Coordinates Framework. This method relies on the online registration of the complex cerebral vascular fingerprint of the studied animal to a pre-aligned reference vascular atlas, thus allowing rapid matching and identification of brain structures. We quantified the accuracy of the automatic registration using super-resolution vascular images obtained at the microscopic scale using Ultrasound Localization Microscopy and found a positioning error of 44 µm and 96 µm for intra-animal and inter-animals vascular registration, respectively. The proposed BPS approach outperforms the manual vascular landmarks recognition performed by expert neuroscientists (inter-annotator errors of 215 µm and 259 µm). Using the online BPS approach coupled with the Allen Atlas, we demonstrated the capability of the system to position itself automatically over chosen anatomical structures and to obtain corresponding functional activation maps even in complex oblique planes. Finally, we show that the system can be used to acquire and estimate functional connectivity matrices automatically. The proposed functional ultrasound on the fly neuro-navigation approach allows automatic brain navigation and could become a key asset to ensure standardized experiments and protocols for non-expert and expert researchers.

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Section: Discussionmentioning

confidence: 99%

Fully-automatic ultrasound-based neuro-navigation : The functional ultrasound brain GPS

Nouhoum

Ferrier²,

Osmanski³

et al. 2021

Preprint

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“…Rungta and colleagues 30 indicated that blue light from the tip of the optic fiber per se could induce neurovascular responses in naïve mice, at irradiances higher than 2 mW ∼ 18 mW.mm −2 . Another recent study reported hemodynamic responses following blue light illumination of the retrosplenial cortex in Thy-ChR2 mice or the illumination of specific neuronal subpopulations of the superior colliculus in other transgenic lines 26 . The authors explained that they used a lower light power and irradiance (0.3 mW ∼1.5 mW.mm −2 ) to prevent non-specific activation.…”

Section: Discussionmentioning

confidence: 99%

“…Like fMRI, ultrafast functional ultrasound imaging (fUS) can provide brain-sized maps of neurovascular activity changes, with a high spatiotemporal resolution (100 µm x 100 µm, 1Hz) even in deep structures (up to 1.5 cm) 23 . This technique has been used to investigate sensory processing in anesthetized 24 , awake [24][25][26] and asleep 27 rodents, and in behaving primates 28,29 . fUS imaging and electrophysiological recordings can, therefore, be used to describe the dynamics of local neuronal activity accurately whilst scanning neurovascular activity over the entire brain.…”

mentioning

confidence: 99%

Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex

Provansal

Labernede

Joffrois

et al. 2021

Preprint

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Optogenetic stimulation of the primary visual cortex (V1) is a promising therapy for sight restoration, but it remains unclear what total cerebral volume is activated after surface stimulation. In this study, we expressed the red-shifted opsin ChrimsonR in excitatory neurons within V1 in rats, and used the fine spatial resolution provided by functional ultrasound imaging (fUS) over the whole depth of the brain to investigate the brain response to focal surface stimulation. We observed optogenetic activation of a high proportion of the volume of V1. Extracellular recordings confirmed the neuronal origin of this activation. Moreover, neuronal responses were even located in deep layers under conditions of low irradiance, spreading to the LGN and V2, consistent with a normal visual information process. This study paves the way for the use of optogenetics for cortical therapies, and highlights the value of coupling fUS with optogenetics.

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“…One of the main current limitations of fUS is its 2D feature, allowing to record a single coronal plane at the same time. While volumetric 3D fUS using 2D matrix array transducers has already been successfully demonstrated in rats 6 and confirmed in mice 7…”

Section: Functional Ultrasound (Fus) Is a Recently Developedmentioning

confidence: 99%

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

Bertolo

Nouhoum

Cazzanelli

et al. 2021

JoVE

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Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity measure of the cerebral blood volume achieved by ultrafast doppler angiography. As brain perfusion is strongly linked to local neuronal activity, this technique allows the whole-brain 3D mapping of task-induced regional activation as well as resting-state functional connectivity, non-invasively, with unmatched spatiotemporal resolution and operational simplicity. In comparison with fMRI (functional magnetic resonance imaging), a main advantage of fUS imaging consists in enabling a complete compatibility with awake and behaving animal experiments. Moreover, fMRI brain mapping in mice, the most used preclinical model in Neuroscience, remains technically challenging due to the small size of the brain and the difficulty to maintain stable physiological conditions. Here we present a simple, reliable and robust protocol for whole-brain fUS imaging in anesthetized and awake mice using an off-theshelf commercial fUS system with a motorized linear transducer, yielding significant cortical activation following sensory stimulation as well as reproducible 3D functional connectivity pattern for network identification.

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A Platform for Brain-wide Volumetric Functional Ultrasound Imaging and Analysis of Circuit Dynamics in Awake Mice

Cited by 76 publications

References 64 publications

Fully-automatic ultrasound-based neuro-navigation : The functional ultrasound brain GPS

Fully-automatic ultrasound-based neuro-navigation : The functional ultrasound brain GPS

Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

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