Manuel Taso1,2,3,4, Pierre-Jean Arnoux2,4, Léo Fradet4,5, Arnaud Le Troter1,3, Jean-Philippe Ranjeva1,3,4, Kathia Chaumoître4,6, Pierre-Hugues Roche4,7, and Virginie Callot1,3,4
1CRMBM UMR 7339, Aix-Marseille Université, CNRS, Marseille, France, 2LBA UMR T 24, Aix-Marseille Université, IFSTTAR, Marseille, France, 3CEMEREM, AP-HM, Pôle d'imagerie médicale, Marseille, France, 4iLab-Spine international associate laboratory, Marseille/Montréal, France, 5Mechanical Engineering, Ecole Polytechnique de Montréal, Montréal, QC, Canada, 6Service de Radiologie, Hôpital Nord, AP-HM, Pôle d'imagerie médicale, Marseille, France, 7Service de Neurochirurgie, Hôpital Nord, AP-HM, Trauma Center, Marseille, France
Synopsis
While
diagnosis of cervical spondylotic myelopathy is easily done with MRI, patient
outcome is still difficult to predict. It is nonetheless associated to a strong
mechanical cause as spinal cord’s (SC) compression is the first event leading
to tissue alterations and neurological deficits. This work proposes an original
approach using biomechanical numerical simulation, to apprehend the mechanisms
of SC compression by the disk, and multi-parametric MRI, to probe the
consequent microstructural alterations (axonal loss, demyelination …).
Thanks
to spatial normalization, first results on 3 patients are presented, allowing co-localization
of personalized simulation of mechanical stress and structural MR alterations.Target audience
Scientists and clinicians involved in spinal cord (SC) MRI and compressive
SC diseases.
Introduction
Cervical spondylotic myelopathy (CSM) is a common SC pathology, whose
diagnosis relies on MRI. It may lead to severe neurological impairment
1.
However, accurate quantitative prognosis biomarkers are still lacking. The
relationship between the mechanical cause of the disease (SC compression) and the
tissue alterations leading to clinical deficits are also unknown. In this context,
biomechanical finite element analysis (FEA), through numerical simulation, is a
promising tool to give some insights into the primary cause of SC tissue
damage. In this work, a proof-of-concept of a unique framework, combining
biomechanical FEA and multi-parametric MRI (mp-MRI), as well as automated MR
post-processing, is proposed to provide new insights into the mechanical origin
of the structural damage encountered in CSM.
Material and methods
Three
patients (1M/2F, age 56±20yo) with cervical myelopathy were included. MRI was
performed at 3T using standard coils, with approval of the Local Ethics
Committee.
mp-MRI
consisted in multi-echo GRE T2*-w sequence (0.5x0.5x5mm3,
5 echoes, 8 slices), monopolar single-shot SE-EPI DTI (30 directions, b=0 and
800s/mm2, 0.9x0.9x10mm3), and HASTE-ihMT sequence2,3
(500 saturation pulses, 500μs each every 1ms, Δf=±7kHz, alternation between single
and dual frequency saturation, 0.9x0.9x10mm3). All images were
acquired with ECG-synchronization, axially, with one slice covering the site of
maximal compression (2 cases at C5/C6, 1 at C4/C5). Mp-MRI metrics were
estimated offline (ihMTR, FA, ADC, $$$\lambda_{//}$$$ and $$$\lambda_{\bot}$$$).
FEA:
a finite element model of the cervical spine (SM2S
– Spine Model for Safety and Surgery)4,5 (fig.1) with biofidel
geometry drawn from in vivo CT for
bones and MRI data (AMU atlases6) for the SC, and including mechanical
properties (viscoelastic for soft tissues, elastoplastic for bone) derived from
in vitro data4,5,7 was used. For each patient, an estimated
compression ratio at the most affected level was calculated based on the T2*-w
MRI and using an invariant database8. To replicate the SC
compression observed with MRI (30, 31 and 36% of the antero-posterior cord
diameter, for patient #1, 2 and 3, resp.) a quasi-static imposed displacement
was applied to the intervertebral disk (IVD) of the concerned functional unit (example
for C5/C6 on fig.1). The computed stresses (Von Mises stress, scalar derived from the stress tensor) were
used to investigate potential damage occurrence.
MRI/FEA combination: for
each case, the outputs of the FEA were projected from a 3D-mesh into a 2D-plane
(to match the MR image acquired at maximal compression site), then scaled and
resampled to match the MR resolution. After mp-MRI normalization
9,
the deformed geometry from the FEA was realigned to the subject’s T
2*-w
slice using affine registration (FLIRT,FSL) and applied to the VM-stress map. Co-localized
VM stress and mp-MRI metrics were then quantified in different WM/GM regions of
interests
9,10 (fig.2b-c).
Results and discussion
Mp-MRI and mechanical stresses for the three cases are presented on fig.3.
Although quantitative comparison has not been performed yet, the simulation
led to morphological deformations that were qualitatively similar to those seen on MR images
(e.g. when comparing GM morphology from the MRI (fig.3b) and stress maps
(fig.3c)). Then, for all patients, it can be seen that higher stresses (red to
light-blue pixels, fig. 3c) were encountered in anterior GM and WM regions (motoneurons
and motor pathways) compared to the posterior regions (p<0.0001 HSD Tukey-Kramer)
and maximal (in average 676±43kPa) in the GM anterior horns. On the MR side, widespread
alterations can be seen (10 to 15% in average as compared to reference control
values11), especially on the FA and ihMTR metrics (fig. 3d,e, vs.
fig. f,g), with similarities between site of maximal MR alterations and maximal
VM stresses (yellow arrows).
While
biomechanical analysis provides some information that could be linked to the
primary lesion occurring, mp-MRI provides sensible markers of tissue
alterations related to primary and secondary lesions. Moreover, the numerical
simulation only gives a static image of the tissular stress encountered, not
taking into account yet the temporal degenerative aspect of the pathology.
Therefore,
the mechanical and structural information appear complementary for a better
understanding of the pathophysiology of CSM. Analysis of other mechanical
parameters (directional stress, pressure) could also provide pertinent
information about specific tissue alterations. Finally, mechanical and MR
analysis distal to the compression site could also help in understanding and assessing
the extent of secondary lesions (e.g Wallerian degeneration12).
Conclusion
A proof-of-concept of a unique framework combining biomechanical FEA and
mp-MRI is proposed. This methodology, applied on a wider cohort, and associated
with longitudinal MR follow-up and multivariate analyses, could potentially
help determining prognostic markers of surgical outcome, reference treatment
for CSM.
Acknowledgements
A*MIDEX ANR-11-IDEX-0001-02References
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