Utilization of Finite Element Analysis Techniques for Adolescent Idiopathic Scoliosis Surgical Planning

Adolescent Idiopathic Scoliosis, a three-dimensional deformity of the thoracolumbar spine, affects approximately 1-3% of patients ages 10-18. Surgical correction and treatment of the spinal column is a costly and high-risk task that is consistently complicated by factors such as patient-specific spinal deformities, curve flexibility, and surgeon experience. The following dissertation utilizes finite element analysis to develop a cost-effective, building-block approach by which surgical procedures and kinematic evaluations may be investigated. All studies conducted are based off a volumetric, thoracolumbar finite element (FE) model developed from computer-aided design (CAD) anatomy whose components are kinematically validated with in-vitro data. Spinal ligament stiffness properties derived from the literature are compared for kinematic assessment of a thoracic functional spinal unit (FSU) and benchmarked with available in-vitro kinematic data. Once ligament stiffness properties were selected, load sharing among soft tissues (e.g., ligaments and intervertebral disc) within the same FSU is then assessed during individual steps of a posterior correction procedure commonly used on scoliosis patients. Finally, the entire thoracolumbar spine is utilized to mechanically induce a mild scoliosis profile through an iterative preload and growth procedure described by the Hueter-Volkmann law. The mild scoliosis model is then kinematically compared with an asymptomatic counterpart. The thoracic deformation exhibited in the mild scoliosis model compared well with available CT datasets. Key findings of the studies confirm the importance of appropriately assigning spinal ligament properties with traditional toe and linear stiffness regimes to properly characterize thoracic spine FE models. Stiffness properties assigned within spinal FE models may also alter how intact ligaments and intervertebral discs respond to external loads during posterior correction procedures involving serial ligament removal, and thus can affect any desired post-surgical outcomes. Lastly, the thoracolumbar spine containing mild scoliosis experiences up to a 37% reduction in global range of motion compared to an asymptomatic spine, while also exhibiting larger decreases in segmental axial rotations at apical deformity levels. Future studies will address kinematic behavior of a severe scoliosis deformity and set the stage for column-based osseoligamentous load sharing assessments during surgical procedures

Reliability and validity of subjective assessment of lumbar lordosis in conventional radiography

Background: Reliability and validity studies of different lumbar curvature analysis and measurement techniques have been documented however there is limited literature on the reliability and validity of subjective visual analysis. Radiological assessment of lumbar lordotic curve aids in early diagnosis of conditions even before neurologic changes set in.Objective: To ascertain the level of reliability and validity of subjective assessment of lumbar lordosis in conventional radiography.Design: A blinded, repeated-measures diagnostic test was carried out on lumbar spine x-ray radiographs.Setting: Radiology Department at Joint Clinical Research Centre (JCRC), Mengo- Kampala-Uganda.Subjects: Seventy (70) lateral lumbar x-ray films were used for this study and were obtained from the archive of JCRC radiology department at Butikiro house, Mengo- Kampala.Results: Poor observer agreement, both inter- and intra-observer, with kappa values of 0.16 was found. Inter-observer agreement was poorer than intra-observer agreement. Kappa values significantly rose when the lumbar lordosis was clustered into four categories without grading each abnormalityConclusion: The results confirm that subjective assessment of lumbar lordosis has low reliability and validity. Film quality has limited influence on the observer reliability. This study further shows that fewer scale categories of lordosis abnormalities produce better observer reliability

3-D visualization and prediction of spine fractures under axial loading

Thesis (Ph.D.)--Boston UniversityVertebral fractures are the hallmark of osteoporosis, yet the failure mechanisms involved in these fractures are not well understood. Current approaches to predicting fracture risk rely on average measures of bone mineral density in the vertebra, which are imperfect predictors of vertebral strength and poor predictors of fracture risk. Prior research has established that substantial regional variations in density exist throughout the vertebra and has suggested several biomechanical consequences of these variations. The overall goal of this dissertation was to characterize failure mechanisms in human vertebrae, with specific emphasis on the role of intra-vertebral heterogeneity in density and microstructure and on identifying clinically feasible techniques for predicting fracture risk. Using images obtained from micro-computed tomography (μCT) and quantitative computed tomography (QCT), the intra-vertebral heterogeneity in bone density was quantified in cadaveric specimens. Quantitative measures of this heterogeneity improved predictions of vertebral strength as compared to predictions based only on mean density. Subsequently, the intra-vertebral heterogeneity in density was measured via QCT in a cohort of post-menopausal women and was found to be lower in those who had sustained a vertebral fracture vs. in age-matched individuals without fracture. The next set of studies focused on assessing the accuracy of finite element (FE) models for predicting vertebral failure. Digital volume correlation (DVC) was used to measure the deformations sustained throughout the vertebra during compression tests. These results were compared against deformation patterns predicted using FE models created from QCT images of the vertebrae. Good agreement was found between predicted and measured deformations when the boundary conditions were accurately defined, despite simplifications made in representing material properties. The outcomes from this dissertation demonstrate that the intra-vertebral heterogeneity in density contributes to bone strength and has promise as a clinically feasible indicator of fracture risk. OCT-based FE models, which by definition account for this heterogeneity, are another promising technique, yet will likely require non-invasive techniques for estimating vertebral loading to provide the requisite accuracy in failure predictions. These two engineering approaches that account for the spatial heterogeneity in density within the vertebra may lead to more sensitive and specific indicators of fracture risk

Machine learning in orthopedics: a literature review

In this paper we present the findings of a systematic literature review covering the articles published in the last two decades in which the authors described the application of a machine learning technique and method to an orthopedic problem or purpose. By searching both in the Scopus and Medline databases, we retrieved, screened and analyzed the content of 70 journal articles, and coded these resources following an iterative method within a Grounded Theory approach. We report the survey findings by outlining the articles\u2019 content in terms of the main machine learning techniques mentioned therein, the orthopedic application domains, the source data and the quality of their predictive performance

Evaluation of Load-To-Strength Ratios in Metastatic Vertebrae and Comparison With Age- and Sex-Matched Healthy Individuals.

Vertebrae containing osteolytic and osteosclerotic bone metastases undergo pathologic vertebral fracture (PVF) when the lesioned vertebrae fail to carry daily loads. We hypothesize that task-specific spinal loading patterns amplify the risk of PVF, with a higher degree of risk in osteolytic than in osteosclerotic vertebrae. To test this hypothesis, we obtained clinical CT images of 11 cadaveric spines with bone metastases, estimated the individual vertebral strength from the CT data, and created spine-specific musculoskeletal models from the CT data. We established a musculoskeletal model for each spine to compute vertebral loading for natural standing, natural standing + weights, forward flexion + weights, and lateral bending + weights and derived the individual vertebral load-to-strength ratio (LSR). For each activity, we compared the metastatic spines' predicted LSRs with the normative LSRs generated from a population-based sample of 250 men and women of comparable ages. Bone metastases classification significantly affected the CT-estimated vertebral strength (Kruskal-Wallis, p < 0.0001). Post-test analysis showed that the estimated vertebral strength of osteosclerotic and mixed metastases vertebrae was significantly higher than that of osteolytic vertebrae (p = 0.0016 and p = 0.0003) or vertebrae without radiographic evidence of bone metastasis (p = 0.0010 and p = 0.0003). Compared with the median (50%) LSRs of the normative dataset, osteolytic vertebrae had higher median (50%) LSRs under natural standing (p = 0.0375), natural standing + weights (p = 0.0118), and lateral bending + weights (p = 0.0111). Surprisingly, vertebrae showing minimal radiographic evidence of bone metastasis presented significantly higher median (50%) LSRs under natural standing (p < 0.0001) and lateral bending + weights (p = 0.0009) than the normative dataset. Osteosclerotic vertebrae had lower median (50%) LSRs under natural standing (p < 0.0001), natural standing + weights (p = 0.0005), forward flexion + weights (p < 0.0001), and lateral bending + weights (p = 0.0002), a trend shared by vertebrae with mixed lesions. This study is the first to apply musculoskeletal modeling to estimate individual vertebral loading in pathologic spines and highlights the role of task-specific loading in augmenting PVF risk associated with specific bone metastatic types. Our finding of high LSRs in vertebrae without radiologically observed bone metastasis highlights that patients with metastatic spine disease could be at an increased risk of vertebral fractures even at levels where lesions have not been identified radiologically

Mechanotransduction impairment in adolescent idiopathic scoliosis

La scoliose idiopathique de l'adolescent (SIA) est une courbure rachidienne tridimensionnelle de plus de 10° qui affecte 4% de la population pédiatrique. L’hétérogénéité de ce désordre musculo-squelettique complexe explique notre incompréhension des causes de la SIA. Néanmoins, plusieurs facteurs biologiques ont été associées à son étiologie. Les réponses osseuses aux stimulations mécaniques normalement appliquées sont nécessaire au fonctionnement optimal du système squelettique. Cependant, la mécanotransduction des tissus musculo-squelettiques dans la SIA est méconnu. L'objectif principal de cette thèse était d'étudier l'apport de la mécanotransduction dans l'étiologie de la SIA au niveau cellulaire et moléculaire. Nous avons étudié les ostéoblastes des patients atteints de SIA et des sujets témoins. L'induction mécanique a été réalisée à l'aide d'une application d'écoulement de fluide oscillatoire. L’immunofluorescence (IF) et la microscopie confocale ont été utilisées pour évaluer les cils, l'actine et les tests fonctionnels. Les modifications moléculaires ont été étudiés par qPCR ou ELISA. Un séquençage d'exome entier sur une cohorte de 73 SIA et 70 sujets témoins appariés a été fait, pour vérifier l'hypothèse que l'accumulation de variants rares dans des gènes impliqués dans la mécanotranduction cellulaire contribueraient à l'étiologie de la SIA. Nous avons découvert une élongation anormale des cils des ostéoblastes SIA, qui étaient significativement plus longs que ceux des sujets témoins dans des conditions de ciliogenèse. Les cellules SIA soumises à une application d'écoulement de fluide, n'ont pas été capable d'ajuster la longueur de leurs cils proportionnellement à la force appliquée. La réponse de l'ajustement de la longueur des cils était significativement différente de celle des ostéoblastes témoins, par des stimulations à court et à long terme.. L'expression des facteurs ostéogéniques était significativement réduite dans les ostéoblastes SIA, suggérant une diminution de la mécanosensibilité. De plus, l'analyse transcriptomique en réponse aux forces appliquées a révélé une altération de l'expression des gènes impliqués dans la voie canonique de Wnt. L'augmentation de la sécrétion du facteur VEGF-A en réponse aux forces appliquées dans les ostéoblastes témoins n'a pas été détectée dans les ostéoblastes SIA. Notre analyse SKAT-O des données du séquençage d’exomes entiers a confirmé l’accumulation de variants rares dans la SIA au niveau de gènes associés à la mécanotransduction cellulaire. Les conséquences de ces anomalies de mécanotransduction ont été étudié par des études cellulaires fonctionnelles, démontrant que les ostéoblastes SIA n’ont pas réussi à se positionner ni à s’allonger proportionnellement au flux bidirectionnel appliqué. Le réarrangement des filaments d'actine induit par l’application d’un flux a été compromis dans la SIA. . Enfin, il a été démontré que le flux de fluide avait un effet inhibiteur sur leur migration. Nos données suggèrent une mécanotransduction altérée dans les ostéoblastes SIA affectant les cils, les voies moléculaires de signalisation, le cytosquelette et le comportement de la cellule en réponse à l'écoulement appliqué. La réponse cellulaire à ces stimulations joue un rôle dans la structure, la force, la forme et le fonctionnement du système squelettique. Etudier le profil de réponse altérée des cellules osseuses scoliotiques peut mener à la conception des approches thérapeutiques plus efficacesAdolescent idiopathic scoliosis (AIS) is a three-dimensional spinal curvature that affects up to 4% of children. As a complex disorder, the cause of AIS is still poorly understood. However, multiple categories of biological factors have been found to be associated with its etiology. The role of biomechanics has been acknowledged by clinicians both in the description of deformity and in relation to bracing treatments. Bone responses to routinely applied forces are an important part in a tightly regulated network that is necessary for the optimal function of the skeletal system. However, little is known about the mechanotransduction of musculoskeletal tissues in AIS. The main goal of this dissertation was to investigate the contribution of mechanotransduction in the etiology of AIS from a cellular-molecular aspect. We studied primary osteoblasts obtained intraoperatively from AIS patients and compared them to samples from trauma cases as controls. Fluid flow application was used for mechanical induction. Immunofluorescence staining, and confocal microscopy was used to assess cilia, actin and cellular tests. Molecular changes were followed using RT-PCR or ELISA. We also performed whole exome sequencing (WES) to test the hypothesis that rare variants accumulation in genes involved in cellular mechanotransduction could contribute to AIS etiology. We found an abnormal cilia elongation among AIS osteoblasts, which grew significantly longer than controls. AIS cells after fluid flow application failed to adjust their cilia length in proportion to the applied force. Under both short- and long-term flow applications, their cilia length adjustment was significantly different from controls. Notably, the elevation in the expression of osteogenic factors, that was normally observed with control osteoblasts, was significantly reduced in AIS osteoblasts, suggesting a decrease in their mechanosensitivity. Moreover, transcriptomic analysis following the applied forces revealed an altered expression of genes involved in the Wnt canonical pathway. Strain induced increase in secreted VEGF-A in control osteoblasts was not detected in AIS flow-conditioned media. At the genomic level, our SKAT-O analysis of the WES data also supported the involvement of heterogenous defects in genes pertaining to the cellular mechanotransduction machinery. We tested the consequence of these mechanotransduction abnormalities in a series of functional cellular studies. As expected and unlike controls, AIS osteoblasts failed to position or elongate themselves in proportion to the bidirectional applied flow. The strain-induced rearrangement of actin filaments was compromised in AIS osteoblasts. Finally, fluid flow showed to have an inhibitory effect on their migration contrasting with control cells that migrated significantly faster under flow. In summary, our data strongly suggest an impaired mechanotransduction in AIS osteoblasts that affect cilia, downstream signaling molecular pathways, cytoskeleton and finally the behaviour of the whole cell in response to flow. Fluid flow is one of the main mechanical forces applied physiologically to the bone cells. Cellular responses to these stimulations play a critical role in the structure, strength, shape and optimal performance of the skeletal system. Mapping the impaired profile response of scoliotic bone cells can help in designing more efficient therapeutic approaches or explaining the mechanisms behind less than optimal bracing outcomes

Idiopathic scoliosis: aetiology, natural history and treatment

EPIDEMIOLOGY: 1 | School Screening for Scoliosis: cohort study of clinical course. 2 | Assessment of Scoliosis is Children - low dose radiographic technique. 3 | Scoliosis in the Community. 4 | School Screening and Pelvic Tilt Scoliois. 5 | Screening for Scoliosis. 6 | Stature and Idiopathic Scoliosis. A Prospective Study. 7 | Scoliosis in the Community. 8 | Screening for Scoliosis: the problem of arm length. 9 | Idiopathic Scoliosis: The Leeds Epidemiology Survey. 10 | The First Year's Follow-up of the MRC Scoliosis Screening Programme.PATHOGENESIS: 11 | The Pathogenesis of Idiopathic Scoliosis - bi-planar spinal asymmetry. 12 | The Pathogenesis of Idiopathic Scoliosis. 13 | Idiopathic Scoliosis in Three Dimensions. 14 | Combined Idiopathic Kyphosis and Scoliosis. An Analysis of the Lateral Spinal Curvatures Associated with Scheuermann's disease. 15 | Aetiology of Idiopathic Spinal Deformities. 16 | The Pathogenesis of Idiopathic Scoliosis. 17 | Scoliosis: How Big Are You? 18 | The Anatomy of Spinal Deformity: A biomechanical Analysis. 19 | Vertebral Shape in the Median Sagittal Plane in Idiopathic Thoracic Scoliosis. A study of true lateral radiographs on 150 patients. 20 | Spinal Growth. 21 | The Aetiology of Spinal Deformities.EXPERIMENTAL SCOLIOSIS: 22 | The Experimental Basis of Idiopathic Scoliosis. 23 | Experimental Structural Scoliosis.CLINICAL APPLICATION: 24 | Conservative Treatment for Idiopathic Scoliosis. 25 | The Surgical Management of Idiopathic Thoracic Scoliosis. 26 | Spinal Deformities in Children. 27 | Operative Surgery for Spinal Deformity. 28 | Idiopathic Scoliosis: Foundation for Physiological Treatment. 29 | Surgical Treatment of Late-onset Idiopathic Thoracic Scoliosis - The Leeds Procedure.MISCELLANEOUS: 30 | The Kyphotic Spine in Myelomeningocele. 31 | Vertebral Body Resection for Spinal Deformity. 32 | Congenital Lumbar Kyphosis in Myelomeningocele - vertebral body resection and posterior fusion. 33 | Cotrel Traction, Exercises, Casting in the Treatment of Idiopathic Scoliosis - a Prospective Controlled Clinical Trial. 34 | Two-Stage Corrective Surgery for Congenital 35 | Deformities of the Spine. Management of Spinal Deformities