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Real time in vivo microstructural assessment based on diffusion MRI and diagnostic application in pediatric neurodegenerative pathologies – PediaRT

MRI virtual biopsy with application to neurodegenerative pathologies

The project proposes a real time tool for in vivo analysis of the brain micro-structure using diffusion MRI, and to make the proof of concept with a diagnostic application in neurodegenerative diseases of the child.

Toward biopsy without surgery

Current MRI techniques allow to infer information relating to the brain microstructure (axon diameters, neuron sizes). The objective is to offer an industrial a software and hardware architecture connected to the MRI that can make this measure during the acquisition so that the doctor has the results at the end of the scan. The impact can be important because it will reduce the duration of the examination, and will thus improve patient comfort and optimize imaging centers radiology slots (and thus increase scanner profitability). By applying this technique to neurodegenerative diseases such as focal epilepsy, we hope to correlate changes in the imaging information to real changes in tissue observed after biopsy. Eventually, the biopsy may be replaced by an MRI, which will improve the care pathway while decreasing the cost of care.

To implement the measures related to the brain microstructure we have conducted numerous software development: 1) to both adapt existing MRI sequences and create new specific ones, 2) to make specific computations in a dedicated application. To be compatible with a real-time strategy, we rethink the algorithms to make them incremental and to distribute them on a high performence computation hardware architecture (cluster) that we put in place to reduce the time to analysis. Sequences and applications verification is done in real conditions of use of MRI in healthy volunteers.

We have developed an infrastructure that connects to a clinical MRI to process data during the acquisition. We have applications to characterize brain tissue: diffusion maps, relaxometry maps, and tractography. We also have tools to estimate axonal diameters ; it has to be integrated in the real-time platform. Discussions with other teams have made ??us aware that our system could also be used in interventional imaging, only requiering the development of suitable applications.

The main steps are: the development of MRI sequences, the parallelization of the algorithms, and the clinical validation. We have the first real time applications (relaxometry, tractography). A positioning study shows that target partners would be small or medium business.During this project new prospects have arised related to interventional imaging: the ability to have real-time results allow the surgeon to better guide its intervention that would both save time and reduce costs.

V. Brion & al., MRI, vol. 31, n° 8, 2013 - image noise filtering (PMID 23659768)
A. Lebois & al., Proc. ISMRM-Workshop, 2013 - estimation of axon diameters
A. Lebois & al., Proc. ISMRM, 2014 - model improvement for the diameter measurement
A. Lebois, PhD thesis dissertation, 2014

In the present project we will develop a system for real-time in vivo brain microstructure studies based on high spatial resolution diffusion Magnetic Resonance Imaging (MRI). This system, designed for any MR scanner, will be more specifically used on clinical MR systems (1.5T, 3T) for the diagnosis of many brain pathologies, especially when the anatomical connectivity of the brain and small lesions of the cortex are involved.
To make the proof of concept, this system will be tested and validated in two challenging conditions: 1) challenging population : real time DTI and tractography in a pediatric population i.e. in patients with a metachromatic leukodystrophy (MLD) that is caused by degeneration of the brain white matter, and in patients with focal epilepsies (FE) induced by small cortical lesions. This real time high resolution platform will make it possible to isolate putative diagnostic biomarkers of these pathologies by taking benefit from the last developments in the domain of diffusion imaging, 2) challenging sequences: implementation on a new very high resolution microscopic DTI approach on healthy volunteers. This real-time microscopic imaging technique will require further validation, with direct comparison with histology on surgical resection specimens in humans (epilepsy surgery, brain tumors…).
Processing data in real-time while scanning will have several important impacts, for instance: a huge decrease of the delay to explore cerebral pathologies; an improvement of the patient comfort, the efficiency of pediatric examinations, and the scanner profitability.
The valorization with an industrial of the real-time MRI microscopy system elaborated in the frame of this project will be considered as a license transfer.

Project coordination

Fabrice POUPON (NeuroSpin/I2BM/Direction des Sciences du Vivant/CEA) – fabrice.poupon@free.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CEA NeuroSpin/I2BM/Direction des Sciences du Vivant/CEA
CEAVALO Cellule Valorisation/Direction des sciences du vivant/CEA

Help of the ANR 249,647 euros
Beginning and duration of the scientific project: January 2013 - 24 Months

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