title: Mapping the dynamics of brain perfusion using functional ultrasound in a rat model of transient middle cerebral artery occlusion.
abstract: Following middle cerebral artery occlusion, tissue outcome ranges from normal to infarcted depending on depth and duration of hypoperfusion as well as occurrence and efficiency of reperfusion. However, the precise time course of these changes in relation to tissue and behavioral outcome remains unsettled. To address these issues, a three-dimensional wide field-of-view and real-time quantitative functional imaging technique able to map perfusion in the rodent brain would be desirable. Here, we applied functional ultrasound imaging, a novel approach to map relative cerebral blood volume without contrast agent, in a rat model of brief proximal transient middle cerebral artery occlusion to assess perfusion in penetrating arterioles and venules acutely and over six days thanks to a thinned-skull preparation. Functional ultrasound imaging efficiently mapped the acute changes in relative cerebral blood volume during occlusion and following reperfusion with high spatial resolution (100 µm), notably documenting marked focal decreases during occlusion, and was able to chart the fine dynamics of tissue reperfusion (rate: one frame/5 s) in the individual rat. No behavioral and only mild post-mortem immunofluorescence changes were observed. Our study suggests functional ultrasound is a particularly well-adapted imaging technique to study cerebral perfusion in acute experimental stroke longitudinally from the hyper-acute up to the chronic stage in the same subject.
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.|SANOFI Research and Development, Lead Generation to Candidate Realization, Chilly-Mazarin, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Brunner
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.
authors.forename: Clothilde
authors.initials: C
authors.lastname: Isabel
authors.affiliation: Molecular Imaging Unit, CIC biomaGUNE, San Sebastián, Spain.
authors.forename: Abraham
authors.initials: A
authors.lastname: Martin
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.
authors.forename: Clara
authors.initials: C
authors.lastname: Dussaux
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Savoye
authors.affiliation: Berlin Stroke Centre, Charité, Berlin, Germany.
authors.forename: Julius
authors.initials: J
authors.lastname: Emmrich
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Montaldo
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mas
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France jean-claude.baron@inserm.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
authors.affiliation: Stroke Research Group, Centre de Psychiatrie et Neuroscience, INSERM U894, Hôpital Sainte-Anne, Paris, France.
authors.forename: Alan
authors.initials: A
authors.lastname: Urban
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D000071937:Cerebral Blood Volume; D059907:Functional Neuroimaging / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging*; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging; D008137:Longitudinal Studies; D010477:Perfusion; D051381:Rats; D015424:Reperfusion; D014463:Ultrasonography / Q000379:methods*
keywords: Cerebral blood volume; functional ultrasound imaging; selective neuronal loss; transient ischemic attack; transient middle cerebral artery occlusion