MSCA-COFUND-CLEAR-Doc-PhD Position #CD22-26: Spinal Cord Injury patient model – Damaged tissue and modelling

This PhD project aims at providing the improved multidisciplinary diagnosis tools which are required for decision making in Spinal Cord Injury (SCI) patient management, from transportation post-injury to rehabilitation. Between 250 000 and 500 000 injuries worldwide with spinal cord injuries (SCI) occur every year and 33% of such lesions lead to tetraplegia or paraplegia. SCI can occur resulting from traumatisms but also degenerative (e.g. myelopathies) or congenital (e.g. Chiari and syringomyelia) diseases. In addition, the occurrence of SCI degenerative pathologies grows with aging population. Among the various forms that SCI can have, cervical SCI are the most severe as they have major medical, psychosocial and financial consequences. Today, SCI patient diagnosis is limited by the time that can be dedicated to examination. This project will investigate the role of Cerebro Spinal Fluid (CSF) in improvement or alteration of SCI patients’ conditions. It aims at developing biomechanical markers associated with the interaction of CSF and meningeal tissues.

Clinical diagnostic and prognostic include cognitive assessment such as an American Spinal Injury Association Impairment score or International Standards for the Neurological Classification of Spinal Cord Injury (Marino et al., 2003; Waring et al., 2010) and imaging investigation when possible. The imaging investigation and acquisitions of SCI patients are limited to suitable time (capacity of the patient to lay still) on the table. CT scan is reported as the gold standard for SCI assessment. However, MRI, while more expensive and time consuming, enables structural investigation of the white and grey matter using specific sequence. Current diagnostic of SCI patients does not take into account the biomechanical tissue damage in which CSF flow, meningeal tissue and spinal cord structure take part. Current guidelines on traumatic SCI management states that early decompression surgery within the first 24 hours should be considered. Type and timing of the pharmacological treatment are also questioned in the early phase of the traumatic SCI but also in degenerative cervical myelopathy (DCM) and in congenital SCI. Development of an adapted rehabilitation is also part of the clinical experts choices. Thus, specific biomechanical markers for SCI patient assessment could be used by clinical expert in decision related to patient management.

The knowledge on the quasi-static behaviour of the structure to model (meningeal tissues) is necessary to develop FSI models. Material properties of the components of the canal have been described in the literature from white and grey matters (Bilston and Thibault, 1996; Karimi et al., 2017; Sparrey and Keaveny, 2011; Yu, 2019) with more recently association with axonal structure, to meningeal tissue (De Kegel et al., 2018; Jin et al., 2014; Shetye et al., 2014). Others components of the canal need to be characterized to enhance current canal simulation. While the micro-structure of the tissue is mostly described through its composition in collagen fibers and elastin, constitutive models usually use one or two fibers populations described by an orientation angle and a coefficient of dispersion. This is to say that mainly all fibers organization could be described by two populations while, especially on meningeal tissue, the full description of the micro-structure is missing. Thus, literature underlines the lack of integration and knowledge on collagen fibers mechanical behaviour into efficient constitutive models, especially.

Simulations of the canal have been reported even including FSI approaches (Cheng et al., 2014). However, such simulations mostly present a limited number of patient-specific canal fluid dynamics without describing association between morphology and CSF dynamics, and nor in the context of SCI except for Chiari and Syringomelia. No report of the canal simulation including damaged tissue mechanical properties neither specific simulation of the components of the canal. In the meantime, multi-scale simulations are reported using homogenization techniques for simulation of others physio-pathological mechanisms such as arterial tissue (Bianchi et al., 2019). An alternative approach to multi-scale modelling is the phenomenological approaches which consists in finding an adequate constitutive model of a material considering the micro-level behaviour of the structure. Such approach has been develop for the creation of an generic constitutive model (Zhang et al., 2019). Multi-scale modelling is then required for simulation of the micro-structure and mechano-biological phenomenon associated with SCI.

This PhD project will be divided into three parts:

• experimental investigation of damaged tissue

• improvement of the cervical spine simulation.

• Pre and post decompression surgery CSF flow simulation

Figure 1. Diagnostic canal morphology tools developed in Sudres’s PhD (3D morphological description (top left graphs), 3D ratio of compression (right corner figures).

Part 1 of the PhD program is the experimental test of damaged tissue after SCI in order to provide numerical simulations with material model enabling to accurately simulate such altered tissues. This concern the spinal cord and the meningeal tissue as well as ligament and nerves. This is a pre-requisite for the simulation of SCI condition and is based on recent meningeal tissue characterization (Evin et al., 2021; Sudres et al., 2021) and previous work from the laboratory (Fradet et al., 2016).

Part 2 of the PhD program aims at integrating the previously performed test within the actual existing model of cervical spine as well as testing by adapted sensitivity analysis the changes in material properties influence. Indeed, while constitutive models have been identified for meningeal tissue in quasi-static, integration to finite element model is missing.

Figure 2. SM2S simulation of the cervical spine including current state of ligaments and nerves simulation from (Beauséjour et al., 2022)

Part 3 of this PhD program is the simulation of pre and post decompression surgery on SCI patients. This will require adapted simulation of the CSF as well as SCI patient anatomy description (Sudres et al., 2020). As simulating CSF flow within the subarachnoidal canal, different approaches could be tested. Homogenization code could be considered to integrate altered tissues material properties.