Project ANR

Brain damages resulting from traumatic brain injury or subarachnoid hemorrhages are a major cause of death and severe disability. The challenge in the patient care is to detect early signs of ischemia to trigger therapeutic measures to prevent further alteration of the brain tissue. The project aims to develop and investigate ultrasensitive Doppler for continuous monitoring of the brain damage in patients. It is coordinated by Dr. Thomas Gaberel in Caen (PHIND lab / CHU Caen), and involves the team of Dr. Thomas Deffieux in our institute. Read more on the ANR website.

This project is coordinated by Serge Picaud at the Vision Institute, and involves the team of Mickael Tanter in our institute Physics for Medicine Paris. The aim is to develop an optogenetic therapy to restore the vision of subjects having lost the eye-to-brain connection as in glaucoma or optic neuropathy. Read more on the ANR website.

Neurodevelopmental disorders result from an impaired brain development, and they affect 1 million newborns in Europe each year. The diagnosis is often performed when the child has reached two or three years old and observable cognitive and behavioral alterations have appeared, because brain functions remain hardly assessed in the early stages of life. The main goal of this project is to deploy functional ultrasound imaging to assess whether functional connectivity could be an early biomarker of perinatal brain diseases. It is coordinated by Charlie Demené, researcher in our institute. Read more on the ANR website.

Neuropathic corneal pain is a dysfunction of the nervous system causing the eye and the face to be oversensitive. This condition remains difficult to treat because its causes are not well known. ConnectPain projects aims to investigate the mechanisms of the pathology, in particular the role of microglia, using a combination of functional ultrasound and connectomics. The project is coordinated by Annabelle Réaux-Le Goazio at the Vision Institute, and involves Sophie Pezet in our institute Physics for Medicine Paris. Read more on the ANR website.

Coronary microcirculation (in vessels smaller than 300µm) plays a key role in the control of cardiac perfusion. Despite an urgent clinical need, there are no techniques available routinely in clinic, to directly visualize the coronary microvasculature and assess the local coronary microvascular system. In CorUS, a novel ultrasound technology will be developed to image the anatomy and the function of coronary vessels at the microscopic scale using a non-invasive and non-ionizing technology. The project is coordinated by Mathieu Pernot, research director in our institute. Read more on the ANR website.

Stiffness is an intrinsic property of soft tissues that reflects the pathological states. Cardiac pathologies, including some types of heart failure, are characterized by a change of myocardial stiffness. Shear wave elastography is an ultrasound-based technique, developed by our researchers, which has allowed for the first time the quantitative assessment of myocardial stiffness in human patients. The objective of this project is to develop a comprehensive mathematical and numerical modeling of 3D Shear-Wave propagation in cardiac realistic physiological models and to demonstrate in vivo that shear velocity can assess important cardiac function and characteristics in experimental pathological models and in patients. The project is coordinated by Sebastien Imperiale of Inria, and involves the team of Mathieu Pernot in our institute Physics for Medicine. Read more on the ANR website.

Recent results demonstrated that gene therapy is an efficient strategy to treat rare or complex diseases of the central nervous system. Delivering therapeutic genes to the CNS mostly relies on Adeno-Associated Viruses (AAVs) vectors that can efficiently, safely and stably transduce neurons following direct intraparenchymal injection. Our goal is to optimize the delivery of AAvs to the central nervous system to make gene therapy safe and accessible to a large number of patients. FAB project aims to demonstrate on animal models the ability of focused ultrasound to open the blood-brain barrier to target specific brain areas with AAVs. The project is coordinated by Jean-François Aubry, research director in our institute. Read more on the ANR website.

Early small-sized blood vessel dysfunctions are increasingly recognized to contribute to the initial stages of many neurodegenerative diseases, such as Alzheimer disease or vascular dementia, before cognitive impairments appear. The development of drugs targeting vascular dysfunctions at its earliest stages could enable the development of novel therapies, but it requires the identification of vascular biomarkers of disease progression for early diagnosis as well as for monitoring drug action. The goal of Peri-fUS project is to probe the alterations of the neurovascular coupling through the assessment of the hemodynamic response function at the earliest possible stage using non-invasive functional ultrasound. The project is coordinated by Thomas Deffieux, researcher in our institute.

Traumatic spinal cord injury can lead to permanent loss of sensation and voluntary motor functions of patients, whose life-long disability is a major public health issue. Fundamental research for spinal cord injury repair have brought important insights into neuro-restoration, but translation to clinical practice is still limited. We propose here a to combine an implantable hydrogel, as a scaffold for tissue remodeling, with a neuroprotective drug, and to use ultrasound neuroimaging to assess the vasculature recovery. The project is coordinated by Fatiha Nothias at Neurosciences Paris-Seine and involves the team of Sophie Pezet in our institute. Read more on the ANR website. 

In synthetic biology, therapeutic bacteria can be designed to target and treat pathologies, such as cancer, directly at the right body location. One limitation of bacterial therapeutic development is the difficulty to observe the growth and behaviors of bacteria in vivo, limiting the possibility to monitor their actions in real time. We propose to address this limitation using ultrasound localization microscopy, a technique developed by our institute which can achieve non-invasive imaging of the vascular system up to microscopic resolution at several centimeter depth. SonoGT project is coordinated by Pascal Hersen at Institut Curie and involves the team of Mickael Tanter in our institute Physics for Medicine. Read more on the ANR website.

Therapeutic approaches of ischemic stroke aim to restore cerebral blood flow. However, in the last decades, while many experimental therapies have been identified in animal stroke models (targeting thrombolysis, neuronal death or inflammation), all have failed when translated to the clinic. This “translational roadblock” is commonly attributed to inherent weaknesses of preclinical studies that include a lack of clinical relevance. The use of preclinical stroke models under anesthesia may explain this failure.The aim of THRONE project is to use functional and molecular imaging methods (ultrasound and MRI) to investigate ischemic stroke in awake animals and to assess the efficacy of therapeutic candidates in models of stroke closed as possible with the clinical situations. The project is coordinated by Denis Vivien at the PhIND lab in Caen, and involves the team of Thomas Deffieux in our institute. Read more on the ANR website.

Assessing our actions and actions of others is essential for behavioral adaptation. In neuroscience, this ability is called performance monitoring. In this project, we use functional ultrasound imaging and ultrasound neurostimulation to investigate the neuronal substrates of performance monitoring in animals, and to dissociate the role of different brain regions. TomFU project is coordinated by Jérôme Sallet at the Stem Cell and Brain Research institute, and involves the team of Jean-François Aubry in our institute Physics for Medicine. Read more on the ANR website.

Neuromodulation is a major tool for treating neurological disorders including pharmaco-resistant depression. Current methods used in clinics rely on electric or magnetic waves, but fail to target deep-seated brain regions non-invasively. In UltraStim project, we propose a neuromodulation technique using a focused ultrasound transducer complemented with an acoustic lens. This technique offers the advantages of being fully non-invasive and low-cost while ensuring a targeting with a millimetric resolution deep in the brain. The project is coordinated by Jean-François Aubry, research director in our institute Physics for Medicine. Read more on the ANR website.