Major Cross-functional project NEIMO

Neuroinflammation is therefore an essential landmark to be monitored for predicting the onset of the neurological disease and assessing how it progresses and responds to treatments. However, procedures to simultaneously map and profile the cellular and molecular states of neuroinflammation are lacking so far. This technological bottleneck is limiting the early diagnosis, the progression assessment, the prognosis of the diseases, and most importantly, early interventional therapies.

This challenge can only be addressed through a collaborative effort between world-leaders in the fields of brain imaging and neuroimmunology. The unique international partnership between Paris Brain Institute and the Yale School of Medicine is ideally suited for this challenge as it combines the strengths of both institutions.

Project

The project will involve eleven principal investigators (PIs), with 5 from Paris Brain Institute and 6 from Yale. Several existing cohorts with large number of patients (>70) with multiple sclerosis, Parkinson’s disease and in prodromal phase of Parkinson's disease will be investigated at Paris Brain Institute and Yale in a coordinated manner through continuous exchange of data. Patients with idiopathic intracranial hypertension will also be investigated. 

The project will: 

1. Monitor early neuroinflammation mechanisms in patients with prodromal Parkinson’s disease and new onset in multiple sclerosis patients;
2. Image brain fluid drainage and neuroinflammation in patients with prodromal Parkinson’s disease, multiple sclerosis patients, and idiopathic intracranial hypertension patients;
3. Build new artificial intelligence tools for the identification of cross-modal (imaging and molecular data) biomarkers;
4. Generate new data-driven disease models integrating neuroinflammation biomarkers.

To maximize the scientific and clinical impact of the project, the developed datasets and approaches will be shared as open science artifacts, for the benefit of a broader scientific community.

This project will help shed light on crucial mechanisms involved in neurodegenerative diseases. It will for the first time ever establish a neuroinflammation monitoring procedure also applicable to other neurodegenerative disorders such as Alzheimer’s disease, brain tumors and brain injuries.  This groundbreaking study will be a world premiere, taking a decisive step towards neuroinflammation control in multiple sclerosis and Parkinson’s disease, leading to earlier and more specific treatments. In addition, this project will help in the identification of the cause of idiopathic intracranial hypertension.

Our collaborative efforts led to several major achievements during the reporting period: 

1. Critical findings from the Yale teams, submitted for publication, on the pathophysiological mechanisms of Parkinson’s disease (Figure1) and multiple sclerosis; 
2. The establishment of the NEIMO magnetic resonance imaging protocol  at PBI and Yale, allowing patient recruitment and NEIMO clinical studies to start at Yale;
3. The high-impact factor publication of a pioneer PBI study on the pathophysiology of idiopathic intracranial hypertension (Figure 2);
4. The generation of novel quantification metrics for multi-tracer studies using TSPO-Positron Emission Tomography (PET) imaging;
5. The automatization of MRI image segmentations for quantitative mapping of meningeal fluid  drainage in humans, a key progress allowing fast processing of MRI scans used in the NEIMO MRI protocol