Lumbar intervertebral disc segmentation for computer modeling and simulation.

BACKGROUND AND OBJECTIVE: The present work had as its main objective the development of a method for localizing and automatically segmenting lumbar intervertebral discs (IVD) in 3D from magnetic resonance imaging (MRI), with the goal of supporting the generation of finite element (FE) models from actual lumbar spine anatomy, by providing accurate and personalized information on the shape of the patient's IVD. The extension of the method to allow performing separate segmentations of the IVD's two main structures - annulus fibrosus (AF) and nucleus pulposus (NP) - as well as automatically detecting degenerated IVD where this distinction is no longer possible was also an objective of the work. METHODS: The method presented here evolves from 2D segmentations in the sagittal profile using Gabor filters towards 3D segmentations. It works by detecting the spine curves and intensity regions corresponding to IVD. As so, the 2D method from Zhu et al. (2013) was partially implemented, modified and adapted to 3D use, and then tested with eight spines from two separated online datasets. The 3D adaptation was achieved by using vertebral body segmentation masks to approximate the shape of the vertebrae and to adjust the spine curves accordingly. RESULTS: The method showed average values of 85%, 83% and 96% for the Dice coefficient, sensitivity and specificity, respectively. The method correctly identified 65 of 68 (96%) IVD as either healthy or degenerated. The method's Dice coefficient is within the range of existing 3D IVD segmentation methods in the literature (81-92%). The method took on average 6-7 s to perform a full 3D segmentation, which is well within the range of the existing methods (2 s - 19 min). CONCLUSIONS: The developed method can be used to generate accurate 3D models of the IVD based on MRI, with AF/NP distinction and detection of marked degeneration by comparing each IVD with the remaining spine levels. Further work shall improve the method towards distinguishing between specific levels of degeneration for clinically oriented FE modeling.

Computational modeling of lumbar disc degeneration before and after spinal fusion.

BACKGROUND: Advancing age and degeneration frequently lead to low back pain, which is the most prevalent musculoskeletal disorder worldwide. Degenerative changes in intervertebral discs and musculo-ligamentous incapacity to compensate sagittal imbalance are typically amongst the sources of instability, with spinal fusion techniques being the main treatment options to relieve pain. The aims of this work were to: (i) assess the link between ligament degeneration and spinal instability by determining the role of each ligament per movement, (ii) evaluate the impact of disc height reduction in degenerative changes, and (iii) unveil the most advantageous type of posterior fixation in Oblique Lumbar Interbody Fusion to prevent adjacent disc degeneration. METHODS: Two L3-L5 finite element models were developed, being the first in healthy condition and the second having reduced L4-L5 height. Different degrees of degeneration were tested, combined with different fixation configurations for Oblique Lumbar Interbody Fusion. FINDINGS: Facet capsular ligament and anterior longitudinal ligament were the most influential ligaments for spinal stability, particularly with increasing degeneration and disc height reduction. Pre-existent degeneration had lower influence than the fusion procedure for the risk of adjacent disc degeneration, being the highest stability and minimal degeneration achieved with bilateral fixation. Right unilateral fixation was more suited to reduce disc stress than left unilateral fixation. INTERPRETATION: Bilateral fixation is the best option to stabilize the spinal segment, but unilateral right fixation may suffice. This has direct implications for clinical practice, and the extension to a population-based study will allow for more efficient fusion surgeries.

Numerical implementation of an osmo-poro-visco-hyperelastic finite element solver: application to the intervertebral disc.

This work deals with the finite element (FE) implementation of a biphasic poroelastic formulation specifically developed to address the intricate behaviour of the Intervertebral Disc (IVD) and other highly hydrated soft tissues. This formulation is implemented in custom FE solver V-Biomech, being the validation performed with a lumbar IVD model, which was compared against the analogous FE model of Williams et al. and the experiments of Tyrrell et al. Good agreement with these benchmarks was achieved, meaning that V-Biomech and its novel poroelastic formulation are a viable alternative for simulation of biphasic soft tissues.

Reply to Comment "Assessing Porous Media Permeability in Non-Darcy Flow: A Re-Evaluation Based on the Forchheimer Equation".

In the name of the authors of the paper "Permeability versus Design in TPMS Scaffolds", published in Materials in 2019 and already counting six citations in Google Scholar to date, I would like to formally respond to the comment manuscript now entitled "Assessing Porous Media Permeability in Non-Darcy Flow: A Re-Evaluation Based on the Forchheimer Equation" [...].

Finite element modelling of the developing infant femur using paired CT and MRI scans.

Bone finite element (FE) studies based on infant post-mortem computed tomography (CT) examinations are being developed to provide quantitative information to assist the differentiation between accidental and inflicted injury, and unsuspected underlying disease. As the growing skeleton contains non-ossified cartilaginous regions at the epiphyses, which are not well characterised on CT examinations, it is difficult to evaluate the mechanical behaviour of the developing whole bone. This study made use of paired paediatric post mortem femoral CT and magnetic resonance imaging (MRI) examinations at two different stages of development (4 and 7 months) to provide anatomical and constitutive information for both hard and soft tissues. The work aimed to evaluate the effect of epiphyseal ossification on the propensity to shaft fractures in infants. The outcomes suggest that the failure load of the femoral diaphysis in the models incorporating the non-ossified epiphysis is within the range of bone-only FE models. There may however be an effect on the metaphysis. Confirmation of these findings is required in a larger cohort of children.

Permeability versus Design in TPMS Scaffolds.

Scaffolds for bone tissue engineering are porous structures that serve as support for cellular growth and, therefore, new tissue formation. The present work assessed the influence of the porous architecture of triply periodic minimal surface (TPMS) scaffolds on their macroscopic permeability behavior, combining numerical and experimental methods. The TPMS scaffolds considered were Schwartz D, Schwartz P, and Gyroid, which have been previously studied for bone tissue engineering, with 70% porosity. On the experimental side, these scaffolds were produced by MultiJet 3D printing and tested for fluid passage to calculate their permeability through Darcy's Law. On the numerical side, finite element (FE) models of the scaffolds were simulated on ABAQUS® for fluid passage under compression to assess potential fluid concentration spots. The outcomes revealed that the design of the unit cell had a noticeable effect on both calculated permeability and FE computed fluid flow velocity, regardless of the identical porosity, with the Gyroid scaffold having higher permeability and the Schwartz P a lower probability of fluid trapping. Schwartz D had the worst outcomes in both testing modalities, so these scaffolds would most likely be the last choice for promoting cell differentiation onto bone cells. Gyroid and Schwartz P would be up for selection depending on the application and targeted bone tissue.

Numerical and experimental evaluation of TPMS Gyroid scaffolds for bone tissue engineering.

The combination of computational methods with 3D printing allows for the control of scaffolds microstructure. Lately, triply periodic minimal surfaces (TPMS) have been used to design porosity-controlled scaffolds for bone tissue engineering (TE). The goal of this work was to assess the mechanical properties of TPMS Gyroid structures with two porosity levels (50 and 70%). The scaffold stiffness function of porosity was determined by the asymptotic homogenisation method and confirmed by mechanical testing. Additionally, microCT analysis confirmed the quality of the printed parts. Thus, the potential of both design and manufacturing processes for bone TE applications is here demonstrated.

Micromechanical study of the load transfer in a polycaprolactone-collagen hybrid scaffold when subjected to unconfined and confined compression.

Scaffolds are used in diverse tissue engineering applications as hosts for cell proliferation and extracellular matrix formation. One of the most used tissue engineering materials is collagen, which is well known to be a natural biomaterial, also frequently used as cell substrate, given its natural abundance and intrinsic biocompatibility. This study aims to evaluate how the macroscopic biomechanical stimuli applied on a construct made of polycaprolactone scaffold embedded in a collagen substrate translate into microscopic stimuli at the cell level. Eight poro-hyperelastic finite element models of 3D printed hybrid scaffolds from the same batch were created, along with an equivalent model of the idealized geometry of that scaffold. When applying an 8% confined compression at the macroscopic level, local fluid flow of up to 20 [Formula: see text]m/s and octahedral strain levels mostly under 20% were calculated in the collagen substrate. Conversely unconfined compression induced fluid flow of up to 10 [Formula: see text]m/s and octahedral strain from 10 to 35%. No relevant differences were found amongst the scaffold-specific models. Following the mechanoregulation theory based on Prendergast et al. (J Biomech 30:539-548, 1997. https://doi.org/10.1016/S0021-9290(96)00140-6 ), those results suggest that mainly cartilage or fibrous tissue formation would be expected to occur under unconfined or confined compression, respectively. This in silico study helps to quantify the microscopic stimuli that are present within the collagen substrate and that will affect cell response under in vitro bioreactor mechanical stimulation or even after implantation.

Evaluation of spinal posture using Microsoft Kinect™: A preliminary case-study with 98 volunteers.

This work proposes a novel approach to assess spinal curvature, by using Microsoft's Kinect™ to obtain 3D reconstructed models of subject's dorsal skin surface in different postures. This method is non-invasive, radiation-free and low-cost. The trial tests here presented intended to evaluate the reliability of this approach, by assessing the tendency of 98 volunteers to present scoliosis. The shoulder height difference was calculated for each subject's scan, by quantifying the angular slope of a line crossing both scapulae. The volunteers' average age was 24.7 years. Results showed that 68.37% of the volunteers revealed differences higher than 1° between the shoulders, having that their record in what concerns to loads and lesions proved to increase the angular slope. This initial approach shall establish the grounds for assessing spinal posture in pre-clinical or industrial ergonomics scans. Further studies shall include comparison versus traditional imaging methods and experienced clinical evaluation.

Combined numerical and experimental biomechanical characterization of soft collagen hydrogel substrate.

This work presents a combined experimental-numerical framework for the biomechanical characterization of highly hydrated collagen hydrogels, namely with 0.20, 0.30 and 0.40% (by weight) of collagen concentration. Collagen is the most abundant protein in the extracellular matrix of animals and humans. Its intrinsic biocompatibility makes collagen a promising substrate for embedding cells within a highly hydrated environment mimicking natural soft tissues. Cell behaviour is greatly influenced by the mechanical properties of the surrounding matrix, but the biomechanical characterization of collagen hydrogels has been challenging up to now, since they present non-linear poro-viscoelastic properties. Combining the stiffness outcomes from rheological experiments with relevant literature data on collagen permeability, poroelastic finite element (FE) models were developed. Comparison between experimental confined compression tests available in the literature and analogous FE stress relaxation curves showed a close agreement throughout the tests. This framework allowed establishing that the dynamic shear modulus of the collagen hydrogels is between 0.0097 ± 0.018 kPa for the 0.20% concentration and 0.0601 ± 0.044 kPa for the 0.40% concentration. The Poisson's ratio values for such conditions lie within the range of 0.495-0.485 for 0.20% and 0.480-0.470 for 0.40%, respectively, showing that rheology is sensitive enough to detect these small changes in collagen concentration and thus allowing to link rheology results with the confined compression tests. In conclusion, this integrated approach allows for accurate constitutive modelling of collagen hydrogels. This framework sets the grounds for the characterization of related hydrogels and to the use of this collagen parameterization in more complex multiscale models.

Biomechanical behaviour of cancellous bone on patellofemoral arthroplasty with Journey prosthesis: a finite element study.

Isolated patellofemoral (PF) arthritis of the knee is a common cause of anterior knee pain and disability. Patellofemoral arthroplasty (PFA) is a bone conserving solution for patients with PF degeneration. Failure mechanisms of PFA include growing tibiofemoral arthritis and loosening of components. The implant loosening can be associated with bone resorption or fatigue-failure of bone by overload. This research work aims at determining the structural effects of the implantation of PF prosthesis Journey PFJ (Smith & Nephew, Inc., Memphis, TN, USA) on femoral cancellous bone. For this purpose, the finite element method is considered to perform computational simulations for different conditions, such as well-fixed and loosening scenarios. From the global results obtained, in the well-fixed scenario, a decrease in strain on cancellous bone was noticed, which can be related to bone resorption. In the loosening scenario, when the cement layer becomes inefficient, a significant increase in cancellous bone strain was observed, which can be associated with bone fatigue-failure.These strain changes suggest a weakness of the femur after PFA.

Long-Term Creep Behavior of the Intervertebral Disk: Comparison between Bioreactor Data and Numerical Results.

The loaded disk culture system is an intervertebral disk (IVD)-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands), which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, eight goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Paul et al., 2012, 2013; Detiger et al., 2013), four of these IVDs were kept in physiological condition (control) and the other four were previously injected with chondroitinase ABC (CABC), in order to promote degenerative disk disease (DDD). The loading profile intercalated 16 h of activity loading with 8 h of loading recovery to express the standard circadian variations. The displacement behavior of these eight IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced finite element (FE) model. The simulations were run on a custom FE solver (Castro et al., 2014). The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in two of the four IVDs. The four control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected). However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles, and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery periods.

Intervertebral disc creep behavior assessment through an open source finite element solver.

Degenerative Disc Disease (DDD) is one of the largest health problems faced worldwide, based on lost working time and associated costs. By means of this motivation, this work aims to evaluate a biomimetic Finite Element (FE) model of the Intervertebral Disc (IVD). Recent studies have emphasized the importance of an accurate biomechanical modeling of the IVD, as it is a highly complex multiphasic medium. Poroelastic models of the disc are mostly implemented in commercial finite element packages with limited access to the algorithms. Therefore, a novel poroelastic formulation implemented on a home-developed open source FE solver is briefly addressed throughout this paper. The combination of this formulation with biphasic osmotic swelling behavior is also taken into account. Numerical simulations were devoted to the analysis of the non-degenerated human lumbar IVD time-dependent behavior. The results of the tests performed for creep assessment were inside the scope of the experimental data, with a remarkable improvement of the numerical accuracy when compared with previously published results obtained with ABAQUS(®). In brief, this in-development open-source FE solver was validated with literature experimental data and aims to be a valuable tool to study the IVD biomechanics and DDD mechanisms.

Systemic lupus erythematosus: association with KIR and SLC11A1 polymorphisms, ethnic predisposition and influence in clinical manifestations at onset revealed by ancestry genetic markers in an urban Brazilian population.

Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belém, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3'UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations.