The spinal cord is a common site for the development of several neurodegenerative
neurological disorders (spinal muscular atrophy or SMA, amyotrophic lateral sclerosis or ALS,
X-linked spinal bulbar muscular atrophy or SBMA). In different proportions, these diseases
involve axonal loss in large funiculi of the spinal white matter, their demyelination, and
loss of ventral horn motor neurons or motoneurones of the spinal gray matter. The lack of
specific biomarkers of these macro and microscopic spinal damages, makes it difficult the
differential diagnosis and monitoring of these diseases.
Techniques to explore non-invasively the human central nervous system, such as magnetic
resonance imaging (MRI) and electrophysiology, are potential tools to extract specific
biomarkers of spinal damages. However, imaging techniques are still poorly developed at
spinal level for technical (specific antennas), anatomical (size of the spinal cord,
vertebrae) and physiological reasons (cardio-respiratory movements). However, recent advances
in the field of spinal cord imaging allowed to extract quantitative data on neuron loss,
axonal degeneration and demyelination in different spinal pathologies whether degenerative
(ALS or SMA) or traumatic (SCI). Correlations were found with clinical data, and in ALS
patients, the changes in MRI metrics over time paralleled the functional deterioration. The
electrophysiological techniques are used since a long time, leading to a good knowledge of
the neurophysiology of human spinal cord. In addition, electrophysiology indirectly provides
data at a microscopic scale, providing information on the excitability of spinal neural
networks and giving an estimate of the amount of functional neurons.
By combining these techniques for the investigation of human spinal cord in vivo, the goal is
to extract new biomarkers using as study models, diseases of the spinal cord affecting
differentially the white and the gray matter (SMA, SBMA and ALS).
At first, new methods of diffusion MRI and modelling will be performed in healthy subjects to
assess the axonal density and diameter of the fibers in the white matter. The anatomical
imaging T2 will measure the geometrical parameters of the spinal cord such as its surface
and/or volume at a given vertebral level. Thanks to imaging, we will construct via methods of
segmentation and image processing, an atlas of the spinal cord that will allow to locate
spatially spinal atrophy in patients. After this phase of validation, A study of patients
will be conducted using these new MRI techniques, in addition to those already developed in
the laboratory. The contribution of electrophysiology will be to assess more accurately the
microscopic damage. Quantitative data from imaging and electrophysiology will be correlated
with clinical data in order to extract the most relevant biomarkers.
This project has thus a methodological interest by proposing the development of new methods
to assess the human spinal cord, at both macro and microscopic levels. These methods are
based on the development of the techniques developed at spinal level and which are already
applicable to human pathologies. The original combination of imaging and electrophysiology
will also enable us to further analyze the human spinal cord, both anatomically and
functionally. This project has an important clinical value for the extraction of biomarkers
in diseases where there is an unmet need for diagnosis, monitoring, prognosis and evaluation
of new therapies.