Pharmaco-fUS: Quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice

Claire Rabut (1) , Jérémy Ferrier (2) , Adrien Bertolo (3) , Bruno Osmanski (3) , Xavier Mousset (1) , Sophie Pezet (1) , Thomas Deffieux (1) , Zsolt Lenkei (2) , Mickaël Tanter (1)

1 PhysMed Paris - Physique pour la médecine
2 IPNP - U1266 Inserm - Institut de psychiatrie et neurosciences de Paris
3 Iconeus

There is a critical need for reliable quantitative biomarkers to assess functional brain alterations in mouse models of neuropsychiatric diseases, but current imaging methods measuring drug effects through the neurovascular coupling, face issues including poor sensitivity, drug-induced changes in global brain perfusion and the effects of anesthesia. Here we demonstrate the proof-of-concept of a minimally-invasive fUS imaging approach to detect the acute cholinergic modulatory effects of Scopolamine (ScoP) on functional brain connectivity in awake and behaving mice, through the intact skull. A machine-learning algorithm constructed an ad-hoc pharmacological score from the ScoP-induced changes in connectivity patterns of five mice. The discrimination model shows important ScoP-induced increase of the hippocampo-cortical connectivity. The pharmacological score led to robust discrimination of ScoP treatment from baseline in an independent dataset and showed, in another independent group, dose-dependent specific effects of central cholinergic modulation of functional connectivity, independent from global brain perfusion changes. In conclusion, we introduce pharmaco-fUS as a simple, robust, specific and sensitive modality to monitor drug effects on perfusion and functional connectivity in the awake mouse brain.

Mots clés: Awake imaging; Drug effects monitoring; Functional biomarker; Functional ultrasound imaging; Support Vector Machine classifier

Domaines: Sciences du Vivant [q-bio]; Neurosciences [q-bio.NC]

Claire Rabut, Jérémy Ferrier, Adrien Bertolo, Bruno Osmanski, Xavier Mousset, et al.. Pharmaco-fUS: Quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice. NeuroImage, 2020, 222, pp.117231. ⟨10.1016/j.neuroimage.2020.117231⟩. ⟨inserm-02971488⟩