1ère journée scientifiques du DHU-Neurovasc
20 mars 2015 - Paris - Espace Scipion
Real-time imaging of brain activity in freely moving rats using functional ultrasound
Alan Urban1,2,5, Clara Dussaux1,2,5, Guillaume Martel1, Clément Brunner1–3, Emilie Mace4 & Gabriel Montaldo1,2
1UMRS 894 INSERM Centre de Psychiatrie et Neurosciences, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 2Optogenetics and Brain Imaging, Stroke Research Team, Paris, France. 3Sanofi Research and Development, Lead Generation to Candidate Realization, Chilly-Mazarin, France. 4Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. 5These authors contributed equally to this work.
Innovative imaging methods help to investigate the complex relationship between brain activity and behavior in freely moving animals. Functional ultrasound (fUS) is an imaging modality suitable for recording cerebral blood volume (CBV) dynamics in the whole brain but has so far been used only in head-fixed and anesthetized rodents. We designed a fUS device for tethered brain imaging in freely moving rats based on a miniaturized ultrasound probe and a custom-made ultrasound scanner. We monitored CBV changes in rats during various behavioral states such as quiet rest, after whisker or visual stimulations, and in a food-reinforced operant task. We show that fUS imaging in freely moving rats could efficiently decode brain activity in real time.
Functional Ultrasound (fUS) imaging of brain hemodynamics in a rat middle-cerebral artery occlusion (MCAo) model of selective neuronal loss (SNL) mimicking transient ischemic attack (TIA)
Clément BRUNNER1,*, Clothilde ISABEL1,*, Abraham MARTIN2, Clara DUSSAUX1, Anne SAVOYE1, Gabriel MONTALDO1, Jean-Claude BARON1,+ and Alan URBAN1,+
1 Centre de Psychiatrie et Neurosciences, INSERM U894, Hôpital Sainte-Anne, Optogenetics and Brain Imaging, Stroke Research Team, Paris, 75014, France.
2 Molecular Imaging Unit, CICbiomaGUNE, Paseo Miramon 182, San Sebastian, Spain.
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 mm), 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.
Cerebral blood volume, functional