Can micro-imaging based analysis methods quantify structural integrity of rat vertebrae with and without metastatic involvement?

Abstract

This study compares the ability of μCT image-based registration, 2D structural rigidity analyses and multimodal continuum-level finite element (FE) modeling in evaluating the mechanical stability of healthy, osteolytic, and mixed osteolytic/osteoblastic metastatically involved rat vertebrae. μMR and μCT images (loaded and unloaded) were acquired of lumbar spinal motion segments from 15rnu/rnu rats (five per group). Strains were calculated based on image registration of the loaded and unloaded μCT images and via analysis of FE models created from the μCT and μMR data. Predicted yield load was also calculated through 2D structural rigidity analysis of the axial unloaded μCT slices. Measures from the three techniques were compared to experimental yield loads. The ability of these methods to predict experimental yield loads were evaluated and image registration and FE calculated strains were directly compared. Quantitatively for all samples, only limited weak correlations were found between the image-based measures and experimental yield load. In comparison to the experimental yield load, we observed a trend toward a weak negative correlation with median strain calculated using the image-based strain measurement algorithm (r=-0.405, p=0.067), weak significant correlations (p<0.05) with FE based median and 10th percentile strain values (r=-0.454, -0.637, respectively), and a trend toward a weak significant correlation with FE based mean strain (r=-0.366, p=0.09). Individual group analyses, however, yielded more and stronger correlations with experimental results. Considering the image-based strain measurement algorithm we observed moderate significant correlations with experimental yield load (p<0.05) in the osteolytic group for mean and median strain values (r=-0.840, -0.832, respectively), and in the healthy group for median strain values (r=-0.809). Considering the rigidity-based predicted yield load, we observed a strong significant correlation with the experimental yield load in the mixed osteolytic/osteoblastic group (r=0.946) and trend toward a moderate correlation with the experimental yield load in the osteolytic group (r=0.788). Qualitatively, strain patterns in the vertebral bodies generated using image registration and FEA were well matched, yet quantitatively a significant correlation was found only between mean strains in the healthy group (r=0.934). Large structural differences in metastatic vertebrae and the complexity of motion segment loading may have led to varied modes of failure. Improvements in load characterization, material properties assignments and resolution are necessary to yield a more generalized ability for image-based registration, structural rigidity and FE methods to accurately represent stability in healthy and pathologic scenarios.

Micro Finite Element models of the vertebral body: Validation of local displacement predictions

“…Moreover, linear microFE models predictions of structural properties have been only validated for input images with 82μm voxel size, leaving unknown their predictive ability if based on images with higher resolution. In particular, considering the ability of this method to account for bone microarchitecture and its potential to analyze the effect of musculoskeletal pathologies and related interventions [33–35], it is very important to understand if the models can accurately predict the local displacements in the elastic regime and provide reasonable estimations of structural properties.…”

A national portfolio of bone oncology trials—The Canadian experience in 2012

“…The Whyne laboratory (University of Toronto) is focused on understanding of biomechanics of musculoskeletal system using translational bioengineering research with emphasis on structural changes in bone involved in metastatic process [34] . They are also performing preclinical and Phase 1 trials assessing effects of photodynamic therapy in metastatic bone lesions [35] .…”

Patient-Specific Bone Multiscale Modelling, Fracture Simulation and Risk Analysis—A Survey

“…Parallel to the work conducted on modelling human bone, there have been efforts to model bone of several animals. Studies range from small animals such as mice [287,[329][330][331][332][333][334][335][336], rats [288,[337][338][339][340][341][342][343] and zebrafish [344], to medium-sized animals such as dogs [345], as well as large animals such as pigs [346][347][348][349][350][351][352], sheep [353][354][355], bovine [220,[356][357][358][359][360][361][362][363] and horses [273,364].…”

“…Research directives within the field of animal bone modelling and analysis include 12A 1 -12A 3 . 12A 1 : Usage of animal bone experimental data to estimate mechanical properties [220,287,288,330,331,340,342,347,363,369] and conception of animal bone failure models [331,338,349,351,356,358,362] that may be similar to human bone failure models [342,344,370]. This directive includes studies in which pathological changes to the skeleton are purposefully induced in test animals by genetic manipulation [371] or malnutrition [332,338,354] in order to create models to study osteoporosis [338,354].…”