09/12/2021
Marie Skłodowska-Curie Actions

MSCA-COFUND-CLEAR-Doc - PhD Position #CD21-29 "CSF based biomechanical markers development for prognostic of Spinal Cord Injury patient"

This job offer has expired


  • ORGANISATION/COMPANY
    Université Gustave Eiffel
  • RESEARCH FIELD
    Medical sciences
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
  • APPLICATION DEADLINE
    21/03/2022 17:00 - Europe/Brussels
  • LOCATION
    France › Marseille
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    35
  • OFFER STARTING DATE
    01/10/2022
  • EU RESEARCH FRAMEWORK PROGRAMME
    H2020 / Marie Skłodowska-Curie Actions COFUND
  • REFERENCE NUMBER
    101034248
  • MARIE CURIE GRANT AGREEMENT NUMBER
    101034248

OFFER DESCRIPTION

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 a framework for prognostic of patients with SCI based on biomechanical markers associated with the interaction of CSF and meningeal tissues. Second objective is thus to prove the hypothesis of CSF role in alteration or recovery of SCI patient.

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 patients 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 physio-pathological mechanisms was found in the literature. 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). Simulations of the physiology have been integrated to such simulation as for blood circulation (Viceconti and Hunter, 2016). 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:

  • sub-arachnoidal canal post-surgical assessment based on simulation of the surgery
  • experimental investigation of the post-surgery mechanisms
  • modelling of such mechanisms.

Part 1 of the PhD program is the numerical planning of the surgery in term of biomechanics. Using the existing refine model of the cervical spine and the diagnosis tool previously developed (Sudres et al., 2020), the results of the decompression surgery will be simulated. Additionally, recent meningeal tissue characterization (Sudres et al., 2021) could also improve the actual cervical spine model.

Part 2 of the PhD program aims at quantify the physical interactions of CSF and meningeal tissue in the sub-arachnoidal space. One experimentation is the measurement of CSF pulsation in embryonic mice as variation of rhythmic activity ubiquitous in immature networks when changing the CSF velocity and second is the measurement in conduction velocity and excitability of motoneurons in in-vitro brainstem- spinal cord-nerve-attached preparation (Pflieger et al., 2002).

Final results will include description of the relationship between changes in pressure/WSS variation in the box/Canal and change in electrical activity.

Part 3 of this PhD program is the simulation of the micro-level mechanisms described in the previous task and integration within physiological simulation. From the previous part, investigated mechanisms will result into a law regulating changes in material properties according with flow. Such regulating law is the association between the relationship between flow and electrical activity and relationship between axonal structure and material properties. Assumption between axonal structure and electrical activity will be needed. As simulating CSF flow, changes in material properties between repetitive simulation could be implemented accordingly. Such methodology has been previously used for modelling of the growth (Driscoll et al., 2009; Shi et al., 2011). Homogenization code will be used to be able to integrate all the simulations of the physio-pathological mechanisms."

More Information

Benefits

  • High-quality doctoral training rewarded by a PhD degree, delivered by Université Gustave Eiffel.
  • Access to cutting-edge infrastructures for research & innovation.
  • Appointment for a period of 36 months based on a salary of 2 700 € (gross salary per month).
  • Job contract under the French labour legislation in force, respecting health and safety, and social security: 35 hours per week contract, 25 days of annual leave per year.
  • International mobility will be mandatory.
  • An international environment supported by the adherence to the European Charter & Code.
  • Access to dedicated CLEAR-Doc trainings with a strong interdisciplinary focus, together with a Career development Plan.

Eligibility criteria

  • At the time of the deadline, applicants must be in possession or finalizing their Master’s degree or equivalent/postgraduate degree. At the time of recruitment, applicants must be in possession of their Master’s degree or equivalent/postgraduate degree which would formally entitle to embark on a doctorate.
  • At the time of the deadline, applicants must be in the first four years (full-time equivalent research experience) of their research career (career breaks excluded) and not yet been awarded a doctoral degree. Career breaks refer to periods of time where the candidate was not active in research, regardless of his/her employment status (sick leave, maternity leave etc). Short stays such as holidays and/or compulsory national service are not taken into account.

  • At the time of the deadline, applicants must not have resided or carried out their main activity (work, studies, etc.) in France for more than 12 months in the 3 years immediately prior to the call deadline.

  • Applicants must be available to start the programme on schedule (around 1st October 2022)

Selection process

Additional comments

  • The First step before applying is contacting the PhD supervisor. You will not be able to apply without an acceptation letter from the PhD supervisor.
  • Please contact the PhD supervisor for any additional detail on job offer.
  • There are no restrictions concerning the age, gender or nationality of the candidates. Applicants with career breaks or variations in the chronological sequence of their career, with mobility experience or with interdisciplinary background or private sector experience are welcome to apply.
  • Support service is available during every step of the application process by email: clear-doc@univ-eiffel.fr

Web site for additional job details

Offer Requirements

  • REQUIRED EDUCATION LEVEL
    Medical sciences: Master Degree or equivalent
  • REQUIRED LANGUAGES
    ENGLISH: Good

Skills/Qualifications

  • At the time of the deadline, applicants must be in possession or finalizing their Master’s degree or equivalent/postgraduate degree.
  • At the time of recruitment, applicants must be in possession of their Master’s degree or equivalent/postgraduate degree which would formally entitle to embark on a doctorate.

Specific Requirements

A 6-month secondment at University of New South Wales, Sydney (Australia).

Work location(s)
1 position(s) available at
Université Gustave Eiffel
France
Marseille
13916
Bd. P. Dramard, Faculté de Médecine secteur-Nord

EURAXESS offer ID: 717622

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