Early brain reorganization of brain circuits after stroke revealed

by functional UltraSound imaging (fUSi)

A collaboration between the team of Dr. Alan URBAN from the Neuro-Electronics Research Flanders institute (NERF empowered by imec, KU Leuven and VIB) and Inserm (Paris) opened way to image reorganization of the brain occurring within minutes after a ischemic stroke. This results were performed using functional UltraSound imaging (fUSi), a breakthrough imaging technology developed at NERF in collaboration with several industrials partners. Ultimately, this work may provide new insights into the clinics to define the most relevant timing for therapy to regain lost functions after stroke.

Each year 6.2 million people worldwide are dying of stroke. Of the ones surviving, over 5 million are permanently disabled and the costs are estimated in 27 billion euros just in Europe and expected to triple by 2030. The most common type of stroke is ischemic (85 %) occurring as a result of an obstruction within a blood vessel supplying blood to the brain. The underlying condition for this type of obstruction is the development of fatty deposits (atherosclerosis) lining the vessel walls. The consequences can vary in severity, but often include permanent paralysis, sensory loss, lack of muscle coordination (ataxia) and partial spatial neglect, among others. To best refine rehabilitation and treatment approaches, we need to understand how the neuronal networks reorganizes after a stroke and when does that start following the initial insult. In this way, it is possible to direct efforts on therapies towards reversibility instead of minimizing progression.

The researchers induced in rats a temporary occlusion of the middle cerebral artery (MCA) that is the main blood vessel that brings oxygen and nutrients to the frontal, parietal and temporal lobes, among other important areas of the brain. Functional ultrasound imaging (fUSi) was then used to followed whisker stimulation-evoked hemodynamic responses during the time the artery was obstructed, as well as after replacing normal circulation by removal of the clip hence mimicking intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) in patients. This study documents a significantly enhanced contralesional hemodynamic responses to unaffected-side whisker pad stimulation, suggesting neuron network reorganization occurring minutes after MCA occlusion in the rat. This enhanced response persisted not only throughout the 1.5-h MCA occlusion period but also during the entire 1.5-h reperfusion recording period, with an apparent trend towards more physiological response as time elapsed.

“This work shed light on ultra-early brain plasticity showing the ability of the brain to reorganize its function in response to stimuli within minutes after a stroke. The next step is to investigate on the underlying cellular and molecular mechanisms. It will be done in collaboration within the Leducq research network unifying teams from 5 different countries (Belgium, USA, Germany, Canada, Israel).” says Clément Brunner, co-first author of the study.

fUSi offers a good spatial and temporal resolution (100 µm, 100ms) and a much better sensitivity than most fMRI scanner that are currently used to diagnose patients. “ Because the fUSi technology is affordable, minimally invasive and easy to use, we believe that fUSi could become a valuable tool for preclinical stroke research as a complement of fMRI or even before electrophysiological recordings. ” confirmed Alan Urban, PI at NERF.

In addition to preclinical studies performed at NERF, the use of fUSi in clinical research will be evaluated in the coming months in patients at UZ Leuven hospital for various applications including neonatal diagnostic imaging and to guide neurosurgeons during tissue resection in glioma and epilepsy.

This project has been funded by a collaborative grant (Network 15CV02 “Protect Stroke”) of the Leducq foundation.

The international grant-making organization comprised of the Fondation Leducq in Paris, the Leducq Foundation for Cardiovascular Research, a US based 501(c)(3) and Leducq Corporation, which is located in Boston, MA and provides administrative services to the grant-making entities. The Fondation Leducq was created with the idea that the battle against cardiovascular and neurovascular disease should be waged at the international level. By forging scientific alliances that transcend national borders and educating young researchers who thrive in an international context, we hope to promote innovation in cardiovascular and neurovascular research, allow researchers to benefit from an efficient use of resources, and develop long term collaborative relationships that will allow us to change the way patients with cardiovascular and neurovascular disease are diagnosed and treated.

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