The role of bone metastases on the mechanical competence of human vertebrae.

Spine is the most common site for bone metastases. The evaluation of the mechanical competence and failure location in metastatic vertebrae is a biomechanical and clinical challenge. Little is known about the failure behaviour of vertebrae with metastatic lesions. The aim of this study was to use combined micro-Computed Tomography (microCT) and time-lapsed mechanical testing to reveal the failure location in metastatic vertebrae. Fifteen spine segments, each including a metastatic and a radiologically healthy vertebra, were tested in compression up to failure within a microCT. Volumetric strains were measured using Digital Volume Correlation. The images of undeformed and deformed specimens were overlapped to identify the failure location. Vertebrae with lytic metastases experienced the largest average compressive strains (median ± standard deviation: -8506 ± 4748microstrain), followed by the vertebrae with mixed metastases (-7035 ± 15605microstrain), the radiologically healthy vertebrae (-5743 ± 5697microstrain), and the vertebrae with blastic metastases (-3150 ± 4641microstrain). Strain peaks were localised within and nearby the lytic lesions or around the blastic tissue. Failure between the endplate and the metastasis was identified in vertebrae with lytic metastases, whereas failure localised around the metastasis in vertebrae with blastic lesions. This study showed for the first time the role of metastases on the vertebral internal deformations. While lytic lesions lead to failure of the metastatic vertebra, vertebrae with blastic metastases are more likely to induce failure in the adjacent vertebrae. Nevertheless, every metastatic lesion affects the vertebral deformation differently, making it essential to assess how the lesion affects the bone microstructure. These results suggest that the properties of the lesion (type, size, location within the vertebral body) should be considered when developing clinical tools to predict the risk of fracture in patients with metastatic lesions.

Bone metastases do not affect the measurement uncertainties of a global digital volume correlation algorithm.

Introduction: Measurement uncertainties of Digital Volume Correlation (DVC) are influenced by several factors, like input images quality, correlation algorithm, bone type, etc. However, it is still unknown if highly heterogeneous trabecular microstructures, typical of lytic and blastic metastases, affect the precision of DVC measurements. Methods: Fifteen metastatic and nine healthy vertebral bodies were scanned twice in zero-strain conditions with a micro-computed tomography (isotropic voxel size = 39 µm). The bone microstructural parameters (Bone Volume Fraction, Structure Thickness, Structure Separation, Structure Number) were calculated. Displacements and strains were evaluated through a global DVC approach (BoneDVC). The relationship between the standard deviation of the error (SDER) and the microstructural parameters was investigated in the entire vertebrae. To evaluate to what extent the measurement uncertainty is influenced by the microstructure, similar relationships were assessed within sub-regions of interest. Results: Higher variability in the SDER was found for metastatic vertebrae compared to the healthy ones (range 91-1030 µÎµ versus 222-599 µÎµ). A weak correlation was found between the SDER and the Structure Separation in metastatic vertebrae and in the sub-regions of interest, highlighting that the heterogenous trabecular microstructure only weakly affects the measurement uncertainties of BoneDVC. No correlation was found for the other microstructural parameters. The spatial distribution of the strain measurement uncertainties seemed to be associated with regions with reduced greyscale gradient variation in the microCT images. Discussion: Measurement uncertainties cannot be taken for granted but need to be assessed in each single application of the DVC to consider the minimum unavoidable measurement uncertainty when interpreting the results.

Experimental validation of a subject-specific finite element model of lumbar spine segment using digital image correlation.

Pathologies such as cancer metastasis and osteoporosis strongly affect the mechanical properties of the vertebral bone and increase the risk of fragility fractures. The prediction of the fracture risk with a patient-specific model, directly generated from the diagnostic images of the patient, could help the clinician in the choice of the correct therapy to follow. But before such models can be used to support any clinical decision, their credibility must be demonstrated through verification, validation, and uncertainty quantification. In this study we describe a procedure for the generation of such patient-specific finite element models and present a first validation of the kinematics of the spine segment. Quantitative computed tomography images of a cadaveric lumbar spine segment presenting vertebral metastatic lesions were used to generate the model. The applied boundary conditions replicated a specific experimental test where the spine segment was loaded in compression-flexion. Model predictions in terms of vertebral surface displacements were compared against the full-field experimental displacements measured with Digital Image Correlation. A good agreement was obtained from the local comparison between experimental data and simulation results (R2 > 0.9 and RMSE% <8%). In conclusion, this work demonstrates the possibility to apply the developed modelling pipeline to predict the displacement field of human spine segment under physiological loading conditions, which is a first fundamental step in the credibility assessment of these clinical decision-support technology.

MicroFE models of porcine vertebrae with induced bone focal lesions: Validation of predicted displacements with digital volume correlation.

The evaluation of the local mechanical behavior as a result of metastatic lesions is fundamental for the characterization of the mechanical competence of metastatic vertebrae. Micro finite element (microFE) models have the potential of addressing this challenge through laboratory studies but their predictions of local deformation due to the complexity of the bone structure compromized by the lesion must be validated against experiments. In this study, the displacements predicted by homogeneous, linear and isotropic microFE models of vertebrae were validated against experimental Digital Volume Correlation (DVC) measurements. Porcine spine segments, with and without mechanically induced focal lesions, were tested in compression within a micro computed tomography (microCT) scanner. The displacement within the bone were measured with an optimized global DVC approach (BoneDVC). MicroFE models of the intact and lesioned vertebrae, including or excluding the growth plates, were developed from the microCT images. The microFE and DVC boundary conditions were matched. The displacements measured by the DVC and predicted by the microFE along each Cartesian direction were compared. The results showed an excellent agreement between the measured and predicted displacements, both for intact and metastatic vertebrae, in the middle of the vertebra, in those cases where the structure was not loaded beyond yield (0.69 < R2 < 1.00). Models with growth plates showed the worst correlations (0.02 < R2 < 0.99), while a clear improvement was observed if the growth plates were excluded (0.56 < R2 < 1.00). In conclusion, these simplified models can predict complex displacement fields in the elastic regime with high reliability, more complex non-linear models should be implemented to predict regions with high deformation, when the bone is loaded beyond yield.

A novel approach to evaluate the effects of artificial bone focal lesion on the three-dimensional strain distributions within the vertebral body.

The spine is the first site for incidence of bone metastasis. Thus, the vertebrae have a high potential risk of being weakened by metastatic tissues. The evaluation of strength of the bone affected by the presence of metastases is fundamental to assess the fracture risk. This work proposes a robust method to evaluate the variations of strain distributions due to artificial lesions within the vertebral body, based on in situ mechanical testing and digital volume correlation. Five porcine vertebrae were tested in compression up to 6500N inside a micro computed tomography scanner. For each specimen, images were acquired before and after the application of the load, before and after the introduction of the artificial lesions. Principal strains were computed within the bone by means of digital volume correlation (DVC). All intact specimens showed a consistent strain distribution, with peak minimum principal strain in the range -1.8% to -0.7% in the middle of the vertebra, demonstrating the robustness of the method. Similar distributions of strains were found for the intact vertebrae in the different regions. The artificial lesion generally doubled the strain in the middle portion of the specimen, probably due to stress concentrations close to the defect. In conclusion, a robust method to evaluate the redistribution of the strain due to artificial lesions within the vertebral body was developed and will be used in the future to improve current clinical assessment of fracture risk in metastatic spines.

Type, size, and position of metastatic lesions explain the deformation of the vertebrae under complex loading conditions.

BACKGROUND: Bone metastases may lead to spine instability and increase the risk of fracture. Scoring systems are available to assess critical metastases, but they lack specificity, and provide uncertain indications over a wide range, where most cases fall. The aim of this work was to use a novel biomechanical approach to evaluate the effect of lesion type, size, and location on the deformation of the metastatic vertebra. METHOD: Vertebrae with metastases were identified from 16 human spines from a donation programme. The size and position of the metastases, and the Spine Instability Neoplastic Score (SINS) were evaluated from clinical Quantitative Computed Tomography images. Thirty-five spine segments consisting of metastatic vertebrae and adjacent healthy controls were biomechanically tested in four different loading conditions. The strain distribution over the entire vertebral bodies was measured with Digital Image Correlation. Correlations between the features of the metastasis (type, size, position and SINS) and the deformation of the metastatic vertebrae were statistically explored. RESULTS: The metastatic type (lytic, blastic, mixed) characterizes the vertebral behaviour (Kruskal-Wallis, p = 0.04). In fact, the lytic metastases showed more critical deformation compared to the control vertebrae (average: 2-fold increase, with peaks of 14-fold increase). By contrast, the vertebrae with mixed or blastic metastases did not show a clear trend, with deformations similar or lower than the controls. Once the position of the lytic lesion with respect to the loading direction was taken into account, the size of the lesion was significantly correlated with the perturbation to the strain distribution (r2 = 0.72, p < 0.001). Conversely, the SINS poorly correlated with the mechanical evidence, and only in case of lytic lesions (r2 = 0.25, p < 0.0001). CONCLUSION: These results highlight the relevance of the size and location of the lytic lesion, which are marginally considered in the current clinical scoring systems, in driving the spinal biomechanical instability. The strong correlation with the biomechanical evidence indicates that these parameters are representative of the mechanical competence of the vertebra. The improved explanatory power compared to the SINS suggests including them in future guidelines for the clinical practice.

Load-sharing biomechanics of lumbar fixation and fusion with pedicle subtraction osteotomy.

Pedicle subtraction osteotomy (PSO) is an invasive surgical technique allowing the restoration of a well-balanced sagittal profile, however, the risks of pseudarthrosis and instrumentation breakage are still high. Literature studied primary stability and posterior instrumentation loads, neglecting the load shared by the anterior column, which is fundamental to promote fusion early after surgery. The study aimed at quantifying the load-sharing occurring after PSO procedure across the ventral spinal structures and the posterior instrumentation, as affected by simple bilateral fixation alone, with interbody cages adjacent to PSO level and supplementary accessory rods. Lumbar spine segments were loaded in vitro under flexion-extension, lateral bending, and torsion using an established spine tester. Digital image correlation (DIC) and strain-gauge (SG) analyses measured, respectively, the full-field strain distribution on the ventral surface of the spine and the local strain on posterior primary rods. Ventral strains considerably decreased following PSO and instrumentation, confirming the effectiveness of posterior load-sharing. Supplemental accessory rods considerably reduced the posterior rod strains only with interbody cages, but the ventral strains were unaffected: this indicates that the load transfer across the osteotomy could be promoted, thus explaining the higher fusion rate with decreased rod fracture risk reported in clinical literature.

Testing the impact of discoplasty on the biomechanics of the intervertebral disc with simulated degeneration: An in vitro study.

Percutaneous Cement Discoplasty has recently been developed to relieve pain in highly degenerated intervertebral discs presenting a vacuum phenomenon in patients that cannot undergo major surgery. Little is currently known about the biomechanical effects of discoplasty. This study aimed at investigating the feasibility of modelling empty discs and subsequent discoplasty surgery and measuring their impact over the specimen geometry and mechanical behaviour. Ten porcine lumbar spine segments were tested in flexion, extension, and lateral bending under 5.4 Nm (with a 200 N compressive force and a 27 mm offset). Tests were performed in three conditions for each specimen: with intact disc, after nucleotomy and after discoplasty. A 3D Digital Image Correlation (DIC) system was used to measure the surface displacements and strains. The posterior disc height, range of motion (ROM), and stiffness were measured at the peak load. CT scans were performed to confirm that the cement distribution was acceptable. Discoplasty recovered the height loss caused by nucleotomy (p = 0.04) with respect to the intact condition, but it did not impact significantly either the ROM or the stiffness. The strains over the disc surface increased after nucleotomy, while discoplasty concentrated the strains on the endplates. In conclusion, this preliminary study has shown that discoplasty recovered the intervertebral posterior height, opening the neuroforamen as clinically observed, but it did not influence the spine mobility or stiffness. This study confirms that this in vitro approach can be used to investigate discoplasty.

Assessing the Mechanical Weakness of Vertebrae Affected by Primary Tumors: A Feasibility Study.

Patients spend months between the primary spinal tumor diagnosis and the surgical treatment, due to the need for performing chemotherapy and/or radiotherapy. During this period, they are exposed to an unknown risk of fracture. The aim of this study was to assess if it is possible to measure the mechanical strain in vertebrae affected by primary tumors, so as to open the way to an evidence-based scoring or prediction tool. We performed biomechanical tests on three vertebrae with bone tumor removed from patients. The tests were designed so as not to compromise the standard surgical and diagnostic procedures. Non-destructive mechanical tests in combination with state-of-the-art digital image correlation allowed to measure the distribution of strain on the surface of the vertebra. Our study has shown that the strains in the tumor region is circa 3 times higher than in the healthy bones, with principal strain peaks of 40,000/-20,000 microstrain, indicating a stress concentration potentially triggering vertebral fracture. This study has proven it is possible to analyze the mechanical behavior of primary tumor vertebrae as part of the clinical treatment protocol. This will allow building a tool for quantifying the risk of fracture and improving decision making in spine tumors.

The Size of Simulated Lytic Metastases Affects the Strain Distribution on the Anterior Surface of the Vertebra.

Metastatic lesions of the vertebra are associated with risk of fracture, which can be disabling and life-threatening. In the literature, attempts are found to identify the parameters that reduce the strength of a metastatic vertebra leading to spine instability. However, a number of controversial issues remain. Our aim was to quantify how the strain distribution in the vertebral body is affected by the presence and by the size of a simulated metastatic defect. Five cadaveric thoracic spine segments were subjected to non-destructive presso-flexion while intact, and after simulation of metastases of increasing size. For the largest defect, the specimens were eventually tested to failure. The full-field strain distribution in the elastic range was measured with digital image correlation (DIC) on the anterior surface of the vertebral body. The mean strain in the vertebra remained similar to the intact when the defects were smaller than 30% of the vertebral volume. The mean strains became significantly larger than in the intact for larger defects. The map of strain and its statistical distribution indicated a rather uniform condition in the intact vertebra and with defects smaller than 30%. Conversely, the strain distribution became significantly different from the intact for defects larger than 30%. A strain peak appeared in the region of the simulated metastasis, where fracture initiated during the final destructive test. This is a first step in understanding how the features of metastasis influence the vertebral strain and for the construction of a mechanistic model to predicted fracture.