MAGNETIC RESONNANCE IMAGING OF THE GLYMPHATIC SYSTEM IN HUMAN – MrGLY

The proposal is based on the postulate that the dynamic volume change of astrocytes contributes to perivascular cerebral spinal fluid (CSF) flow regulation, recently described as the glymphatic system. We thus postulate that those cell volume changes could be monitored through Water Diffusion Magnetic Resonance Imaging (DW-MRI). Our aims are:
1. To investigate, from rodent to non-human primate models, the dynamics of the glymphatic system / intracerebral CSF flows by using different modalities
2. To establish a non-invasive MR biomarker of glymphatic activity to be used in Humans
3. To show, in Humans, a link between this biomarker and a marker of early amyloidosis
4. To validate the clinical use of this biomarker for the diagnosis of brain diseases.
To succeed in meeting these objectives, we will combine the expertises of leading groups in the fields of diffusion MR imaging (NeuroSpin, CEA-Saclay - Denis Le Bihan), of neurovascular disorders and brain imaging (Inserm UMR-S U1237, GIP Cyceron – Denis Vivien) and in the physiology of the neuro-glio-vascular interface (CNRS UMR 8246, NPS – Bruno Cauli and Dong Li).
The expected results are of different orders. The first result expected in the short term is a better understanding of the importance of the cerebrospinal flows / glymphatic system in brain functions and dysfunctions, not only in rodents but also in non-human primates. Combined with future drug therapies capable of modulating the efficacy of the glymphatic system this will reduce the incidence and thus ultimately improve the prognosis of patients suffering of acute and chronic brain disorders, such as stroke and Alzheimer’s disease, respectively.
At large Expectations: Beyond basic research and possibly translational approaches, functional diffusion weight imaging (DW-MRI) developed in the framework of our project to reveal the glymphatic system in Human without contrast agent, could be translated in clinics in the future. Our innovative techniques could be implemented for conventional radiology. Nevertheless, we are aware that this translational study is only a first stage and that the way to go to clinic applications is a long and difficult process, with unexpected aspects still to solve.