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Comprehensive experimental and computational mechanical characterisation of metastatic vertebrae

Periodic Reporting for period 1 - METASPINE (Comprehensive experimental and computational mechanical characterisation of metastatic vertebrae)

Reporting period: 2019-09-01 to 2021-08-31

Lytic spinal metastases are frequent in cancer patients and can weaken vertebrae, increasing the risk of fracture and leading to spine instability. Qualitative scoring systems are used by oncologists and orthopaedic surgeons to decide if the metastatic vertebrae need to be surgically treated. However, these guidelines are not accurate for all those patients with middle-size lesions. An accurate, quantitative and mechanistic computational model would improve the prediction of the risk of fracture in these patients. However, such models need first to be validated against well-controlled experiments in the laboratory.
The main goal of METASPINE was to develop and validate FE models to study the effect of lytic metastatic lesions on the mechanical properties of spine segments. This goal was achieved by combining the excellent skills in experimental characterization of spine segments by the researcher (Dr Marco Palanca) with the cutting-edge expertise of the host institution (University fo Sheffield, Dr Enrico Dall’Ara) in imaging and computational modelling.
The objectives of the study were:
1. To develop an experimental approach to measure the full-field strain maps under multi-axial loading in spine segments with and without metastatic lesions, combining high- resolution biomedical imaging, mechanical tests, and image processing techniques;
2. To develop a procedure to generate computational models of the spine segments with and without simulated metastatic lesions based on medical images and to validate the outputs of the models using the experimental data obtained in the project;
3. To evaluate the effect of lytic lesions on the structural and local mechanical properties of the spine segments in function of the lesions’ features, such as size and position.
4. To train the researcher in imaging, image processing and computational modelling for biomechanical applications.

The project reached most of the objectives and added activities to maximize the scientific and clinical impact of the research.
This project was divided into an experimental and a computational component, to comprehensively understand the effect of metastatic lesions on the mechanics of the vertebrae.

We have developed a pipeline to perform high resolution scans (micro-computed tomography, microCT) that combines in situ mechanical tests of spine segments within a microCT scanner and displacement and strain measurements inside the vertebral body through a global Digital Volume Correlation approach. We have also developed a procedure to induce mechanical lesions that simulate lytic lesions and used the experimental pipeline to understand the effect of the lesions on the deformation of the bone. METASPINE was the first study where the strain fields were evaluated in the internal trabecular tissue of vertebrae with and without mechanically induced lesions. A differential analysis enabled the identification of complex heterogeneous displacement and strain distributions induced by the lesions, as reported in details in Palanca et al., Plos One, 2020.

From the computational point of view, we have generated, validated, and applied computational models to predict the mechanical behavior of vertebrae with metastases. Two different modelling pipelines have been developed to account for the complex heterogeneous structure of the vertebral bodies, or to estimate the bone mechanical properties from clinical images. We have shown that the models can predict very accurately the deformation of the bone under complex loading, as detailed in Palanca et al., J Mech Behav Biomed Mat, 2021.

Finally, we have evaluated the effect of the parameters of the lesions (size and position) on the mechanical properties of the vertebral bodies by combining biomedical imaging, mechanical testing and image correlation techniques. In particular we have shown that the size and position of the lesion can explain 72% of the variability in the mechanical properties, better than standard available clinical tools. Details can be found in the paper Palanca et al., Bone, 2021.

The results of the project have been published in three papers in peer reviewed international journals and in several national and international conferences.
The project has trained an experienced researcher in spine biomechanics. The researcher gained skills in generating and validating computational models of healthy and metastatic spines and in biomedical imaging. These new skills together with his previous background in experimental spine mechanics formed him as an expert of spine biomechanics. Moreover, the researcher gained expertise in clinical aspects of bone metastases, which allowed him to become an expert of bone metastases biomechanics.

The developed standards in testing specimens and developing computational models will push the research in spine biomechanics and modelling. We have shared in the public domain all experimental and computational datasets so that other research groups can use them to validate the models that they have developed.
The pipelines for generating and validating microFE models are being converted into web-application sharable among the members of The University of Sheffield and external collaborators. The results have been disseminated by the researcher and the scientist in charge to different research communities, including experts in biomechanics, medicine and biology of metastastic bones. The methodologies developed during the project can be widened and shared with other researcher to be used on different anatomical sites.
Finally, there is potential clinical impact, as we have shown for the first time the relationship between the mechanical properties of metastatic vertebrae and the size and position of the lesions. While these findings will have to be confirmed on a larger dataset, they suggest that we need to improve the current clinical scoring systems to evaluate the risk of fracture in patients with vertebral lesions.
Overview of the project deliverables
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