Image-informed BIOmechanical brain tumor forcast MOdelling (IBIOMO): Malignant transformation of Low Grade Astrocytoma (LGA)
Grade 3 and 4 Astrocytomas are high grade gliomas (HGG) that usually result from initially less aggressive low grade gliomas (LGG) through malignant transformation (MT). This process has various definitions in the literature, clinical and histopathological, depending on the scale of the study and researchers' interest. In this work, we study a biological hypothesis that could explain the spatial progression of low grade astrocytoma (LGA) during MT. The former hypothesis will be tested on LGA patients through tumor segmentation and patient specific parameters from Medical Resonance Images (MRI) and a mechanistic growth model.
This work is funded by the Institute of Advanced Study (IAS) of the University of Luxembourg.
Team:
PI: (Prof) Stéphane P. A. Bordas
Post-doctoral researcher: Dr. Stéphane Urcun
PhD candidate: Meryem Abbad Andaloussi
Experimental Insigts into Tissue Injury: Integrative Modeling of Mechanical and Biomechanical Factors
Tissue deterioration and death commonly occur during long-term hospitalisation. However, some patients develop tissue injury within less than a week. The onset of such a phenomenon has been associated with severe tissue loading (either in terms of amplitude or duration). Bedsores, ulcers and oedema are similar to bruises on an apple. Oxygen deprivation is also an important factor for the onset of tissue death. Deprived of oxygen, the tissue structure suffers and the tissue “suffocates to death.”
Generally, mathematical models do not account for the interplay between both of the above two phenomena, whilst they are known to interact with each other. The objective of our work is to understand the most important mechanical (loading) and bio-chemical (oxygen deprivation) factors responsible for loss of tissue integrity and to couple those within a single model.
A unique aspect of our study is to consider tissue death at several spatial and temporal scales. Bio-chemical processes generally occur at the microscopic scale, whereas the mechanical loading is active at the macroscopic scale. As in the case of the bruised apple, the consequences of external loading is visible with the naked eye: interaction of a tissue with an external device (wheel-chair, mattress, prosthesis).
We use the following methods: 1) experimental observation, characterisation (from existing experiments); 2) Modelling and evaluation. Hence, an experimental campaign was conducted on mice, where soft tissue injury was introduced (as in the case of the apple). Experimental results will allow both the identification of parameters of the model to describe properly the tissue, and the evaluation of the model to assess model reliability.
This study will be the basis for future work on animals before moving to organs on chip and humans. It will allow us to make one step toward the next generation patient-specific experimental-mathematical-computational pipeline. This pipeline could become a backbone for a deeper understanding of tissue biophysics and mechanics, enable diagnosis and predictions.
Societally, our work has the potential to decrease the burden of ulcers, bedsores and tissue damage in general on patients (wheelchair, mattresses, prosthesis, etc.). Scientifically, we will deliver open access software, data sets and protocols to accelerate future work in computational biomechanics.
Team:
PI: (Prof) Stéphane P. A. Bordas
Post-doctoral researcher: Dr. Stéphane Urcun
PhD candidate: Thomas Lavigne
S-KELOID Understanding Keloid Disorders: A multi-scale in vitro/in vivo/in silico approach towards digital twins of skin organoids on the chip
Keloid is a fibrotic tissue that is proliferating beyond the primary injured area and persisting over time without natural regression. Despite the variety of treatments available, no effective therapeutic protocols or standardized guidelines have been published yet. S-Keloid project gathers clinicians, biologists, computational scientists and mathematicians to propose the multi-scale modeling -from in-vitro to in-vivo- of the mechano-biological characteristics of keloids.
The SKeloid is funded by ANR (France) and FNR (Luxembourg).
Team:
PI: (Prof) Stéphane P. A. Bordas
Post-doctoral researcher: Dr. Stéphane Urcun
PhD candidate : Yasmine El Mahi (Besançon, FR)