Computer aided method for 3D assessment of the lower limb alignment for orthopedic surgery planning

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2017Os membros inferiores são responsáveis por fornecer suporte à totalidade do corpo humano e são essenciais nas mais variadas tarefas como estar de pé, andar e correr. Por vezes, e devido a diversos motivos, podem existir defeitos ou deformações nos membros inferiores que têm um impacto direto na qualidade de vida de uma pessoa, quer por se ver afetado o lado estético pessoal ou por condicionar significativamente a mobilidade. Uma característica da estrutura do membro inferior que é diretamente afetada por estas deformações é o seu alinhamento, isto é, a posição relativa dos ossos e articulações que compõem o membro. Graças à evolução da medicina moderna, corrigir estas deformações é agora uma prática bastante comum no campo da cirurgia ortopédica. No entanto, antes de qualquer cirurgia corretiva e até de qualquer planeamento que esta exija, a deformação tem de ser corretamente analisada, o que é feito através da chamada avaliação do alinhamento do membro inferior. Atualmente, num contexto clínico, esta avaliação é feita manualmente num espaço de trabalho bi-dimensional, normalmente utilizando apenas imagens de raios-X da perna inteira no plano anatómico frontal. Uma revisão ao estado da arte no que toca a métodos de planeamento cirúrgico dedicados ao membro inferior permite concluir que de facto existe software capaz de realizar este planeamento, mas que, no entanto, para além de terem custos elevadíssimos associados, nenhum utilizada modelos 3D como fonte de informação, o que traria imensos benefícios, especialmente ao nível da informação acerca da rotação e da inclinação dos ossos. Existem no entanto algum software a um nível mais experimental que utiliza modelos 3D para realizar a avaliação do alinhamento do membro inferior, sendo que nenhum deles passou ainda a estar disponível comercialmente. Numa perspetiva de implementar um método automático baseado em computador para realizar o planeamento pré-cirurgico da cirurgia de correção para ser utilizado em contexto clínico, foi proposto um projeto para o desenvolvimento de um novo software capaz de efetuar a avaliação do alinhamento do membro inferior em modelos 3D dos doentes. O projeto foi dividido em quatro etapas distintas que se desenrolaram ao longo de um estágio de sete meses. Na primeira etapa, o objetivo consistiu em gerar diversos modelos 3D dos membros inferiores de diferentes pacientes. Para tal, recorreu-se ao software de segmentação de imagens médicas Mimics 14.0 e utilizaram-se imagens de tomografia computorizada dos pacientes. Após o processo de segmentação, obtiveram-se os modelos 3D cuja qualidade teve de ser assegurada através de um processo de remeshing e cuja correta orientação espacial teve de ser também assegurada, já que a avaliação do alinhamento é sensível à orientação da perna. Para tal, utilizou-se o software de renderização 3D Geomagic Studio 14. Optou-se ainda por separar os modelos dos ossos nas suas porções proximal e distal, de modo a reduzir futuramente os tempos de computação. Findo todo este processo, assegurou-se que diferentes utilizadores poderiam gerar estes modelos sem grande variabilidade ou erro no resultado final através da comparação dos modelos obtidos de um mesmo paciente por três utilizadores distintos, sendo que os modelos obtidos apresentavam volumes com diferenças inferiores a 1% relativamente ao valor médio e com um baixo desvio padrão. Numa segunda etapa, os ângulos e medidas consideradas necessárias para uma avaliação adequada foram definidos, apresentando os valores esperados para estas medidas de acordo com a literatura. Assim, foi possível definir também os pontos anatómicos que são necessários para a definição destes mesmos ângulos e medidas e que portanto têm de ser encontrados pelo software. Na terceira etapa, fez-se então o desenvolvimento propriamente dito do software. Encontravam-se já disponíveis alguns métodos automáticos desenvolvidos no contexto projeto, contudo, estes métodos exigiam que o utilizador conhecesse as ferramentas do Geomagic de modo a obter algumas informações, e que depois fosse capaz de utilizar estas informações para editar os scripts de modo a que estes funcionassem para cada paciente em específico. Para além disso, apenas pontos muito específicos podiam ser encontrados. Nesse sentido, isto é, de modo a que todo o processo de encontrar os pontos anatómicos relevantes pudesse ser feito diretamente pelo utilizador, no programa, e sem exigir quaisquer conhecimentos de programação, um conjunto de técnicas foi implementado, dando ao programa uma grande componente gráfica. Para os diferentes pontos, foi necessário recorrer a diferentes metodologias, algumas desenvolvidas propositadamente para o efeito e implementadas em linguagem de programação Python "pura", e algumas adaptadas de outras já existentes e disponíveis no próprio Geomagic. Foi ainda assegurado que existiam métodos alternativos caso os métodos padrão não fossem os mais adequados devido a uma estrutura diferente da esperada dos próprios modelos 3D. De todo este processo resultou um programa que usa os modelos 3D gerados e, da maneira mais automática possível e com uma interface do utilizador fácil de usar, fornece todos os ângulos e medidas, efetuando assim a dita avaliação do alinhamento do membro inferior em 3D. Uma análise ponderada aos resultados obtidos permitiu identificar quais os pontos anatómicos que estarão a ser obtidos de maneira menos ideal e por isso a levar a alguns resultados não tão bons como o esperado. A dependência criada da seleção e limitação de certas áreas nas quais ocorre uma iteração que permite encontrar certos pontos é possivelmente a maior falha do programa desenvolvido que se torna assim demasiado sensível ao input do utilizador. Note-se, contudo, que os próprios testes apresentam algumas falhas que podem influenciar os resultados obtidos, tal como não ter sido definido um roteiro de teste que obrigasse a uma utilização uniforme por parte de todos os utilizadores, e também os diferentes níveis de experiência com o programa por parte dos utilizadores de teste. No entanto, a maioria das medidas obtidas apresenta valores constantes ao longo de diversas utilizações, igualando os valores que seriam obtidos manualmente, mas com o potencial de os obter em metade do tempo. Pode concluir-se então que, no momento, a avaliação do alinhamento 3D é possível utilizando o software desenvolvido. É possível ainda apontar algumas limitações e fazer algumas sugestões de modo a que estas sejas ultrapassadas. Algumas limitações partiram do facto da experiência a programar em Python ser bastante limitada, e outras partiram do software utilizado para fazer o desenvolvimento. Por exemplo, o método que teria sido o mais indicado para encontrar um certo número de pontos na Tibia não foi possível de implementar devido a um bug interno do software. Existe ainda muita coisa que pode ser feita no que toca ao software desenvolvido e ao objectivo final de desenvolver um método de planeamento pré-operativo: em primeiro lugar, é necessário realizar mais testes, de modo a aumentar o tamanho da amostra e o intervalo de confiança dos testes; em segundo lugar, eliminar a dependência do Geomagic para utilizar o programa seria o ideal; finalmente, de modo a completar o plano inicial, deve ser implementada a possibilidade de visualizar o resultado da cirurgia nos modelos 3D.The lower limbs are responsible for supporting the body and are essential for several tasks such as standing, walking and running. Sometimes, and due to various reasons, defects or deformities can be found on the lower limbs and this has an impact on a person’s quality-of-life. One characteristic of the structure of the lower limb that is affected by these deformities is its alignment, i.e. the relative positions of the bones and joints that it includes. Thanks to the evolution of modern medicine, fixing these deformities is now a common practice in the orthopedics' surgical field. Before any corrective surgery and its respective planning, the deformity needs to be properly analyzed, which is accomplished by the assessment of the alignment of the whole lower limb. Currently, in clinical setting, this assessment is carried out manually in the two-dimensional space, normally using wholeleg X-ray images of the anatomical frontal plane, but complex deformities can not be assessed properly in a 2D image. In a desire to create an automatic computer-based method for the preoperative planning of deformity correction and knee surgery, a project consisting of developing a new software for assessing the lower limb alignment based on 3D models was proposed. The project was comprised of four stages: In the first stage, 3D models of different patients’ lower limbs were generated using both segmentation and 3D rendering software, and it was ensured that these models could be generated by any user without significant variability/error in the final outcome; In the second stage, the exact angles and measures needed for a proper assessment were defined, as well as the anatomic landmarks required to calculate them that should then be found by the software; During the third stage, the software development took place, from which resulted a program that uses the generated 3D models and, in the most automatic way possible and with an easy-to-use interface, returns all the needed angles and measures; The final stage of the project was to ensure that the program is reliable and consistent in its results in both intraobserver and interobserver domain, and that it composes an improvement when compared with the manual procedure, while also ensuring that the results obtained by using the program match those obtained manually. A lot can still be done and improved regarding the developed software and the ultimate goal of fully developing a preoperative planning method, but, so far, the 3D alignment assessment that results from the program has been considered to perform its task properly and in an improved way when compared to the traditional technique, even though some limitations can be observed

Introduction of a bone-centered three-dimensional coordinate system enables computed tomographic canine femoral angle measurements independent of positioning

Introduction: Measurement of torsional deformities and varus alignment in the canine femur is clinically and surgically important but difficult. Computed tomography (CT) generates true three-dimensional (3D) information and is used to overcome the limitations of radiography. The 3D CT images can be rotated freely, but the final view for angle measurements remains a subjective variable decision, especially in severe and complex angular and torsional deformities. The aim of this study was the development of a technique to measure femoral angles in a truly three-dimensional way, independent of femoral positioning. Methods: To be able to set reference points in any image and at arbitrary positions of the CT series, the 3D coordinates of the reference points were used for mathematical calculation of the angle measurements using the 3D medical imaging Software VoXim®. Anatomical reference points were described in multiplanar reconstructions and volume rendering CT. A 3D bone-centered coordinate system was introduced and aligned with the anatomical planes of the femur. For torsion angle measurements, the transverse projection plane was mathematically defined by orthogonality to the longitudinal diaphyseal axis. For varus angle measurements, the dorsal plane was defined by a femoral retrocondylar axis. Independence positioning was tested by comparison of angle measurement results in repeated scans of 13 femur bones in different parallel and two double oblique (15/45°) positions in the gantry. Femoralvarus (or valgus), neck version (torsion), and inclination angles were measured, each in two variations. Results: Resulting mean differences ranged between –0.9° and 1.3° for all six determined types of angles and in a difference of <1° for 17 out of 18 comparisons by subtraction of the mean angles between different positions, with one outlier of 1.3°. Intra- and inter-observer agreements determined by repeated measurements resulted in coefficients of variation for repeated measurements between 0.2 and 13.5%. Discussion: The introduction of a bone-centered 3D coordinate system and mathematical definition of projection planes enabled 3D CT measurements of canine femoral varus and neck version and inclination angles. Agreement between angular measurements results of bones scanned in different positions on the CT table demonstrated that the technique is independent of femoral positioning

Nanofibrous Disc-Like Angle Ply Structure for Total Disc Replacement in a Small Animal Model

Low back pain affects 85% of the population and carries a socioeconomic price tag of $100 billion USD per year. Lumbar intervertebral disc disease is strongly implicated as a causative factor in back pain, as degeneration, which is ubiquitous in the population, leads to loss of normal spine function. For these reasons, our lab has developed disc-like angle ply structures (DAPS) for total disc replacement. These cell-seeded replacements are designed to match the natural hierarchical structure and function of the native disc and correct spinal kinematics after end-stage disc disease. In this dissertation, I describe the development of a rat caudal spine (tail) model of total disc replacement as a platform to evaluate DAPS in vivo; an external fixation system that immobilized caudal vertebrae at the site of implantation was required for DAPS retention and a radiopaque scaffold was developed to confirm intervertebral DAPS positioning. A detailed analysis of the DAPS in vitro growth trajectory was performed to select the optimum pre-culture duration before implantation. Cell-seeded DAPS were subsequently implanted in the rat tail and evaluated by histological, mechanical, and MRI analyses. DAPS successfully restored the mechanical properties of the native motion segment in compression, providing the first evidence of the efficacy of engineered disc replacements. Adaptations of the implant to the in vivo environment were identified; there was a reduction in glycosaminoglycan after implantation, structural modifications to the NP material, and no evidence of vertebral integration. In tackling the first of these issues, a pre-culture strategy that primed DAPS for the in vivo environment was developed; using a rat subcutaneous model, implant phenotype was best conserved post-implantation using a pre-culture strategy with a transient high dose of TGF-b3. Future work will address maintenance of NP structure, vertebral integration and scaling up to human sizes. In my work, the most promising finding was that DAPS replicated compressive motion segment mechanical properties after implantation supporting the idea that engineered biological disc replacement is a possibility for clinical treatment of advanced disc disease

The relationship of femoral torsion and lower limb injury

Research about femoral torsion has existed since the late 1980’s with the focus on developing a method to measure femoral torsion. Identifying the degree of femoral torsion has become important because excessive antetorsion of the femur has been associated with hip pathology. In addition, it is important to identify the degree of femoral torsion prior to placement of a hip prosthesis and prior to derotational osteotomy for children with congenital excessive femoral antetorsion, which is seen in cerebral palsy, hip dysplasia and Blount’s disease. The gold standard for measuring femoral torsion is a CT scan, which is invasive therefore limiting its usage especially in children. While research on femoral torsion has been narrowed to hip pathology and correcting deformity, excessive femoral antetorsion is thought to impact structures distal to the hip therefore increasing the risk of developing lower limb injury. Since the relationship between femoral torsion and lower limb injury is unknown, a systematic review is presented in Chapter 2 that looked at the relationship between femoral torsion and other hip characteristics as a risk factor for lower limb injury. Excessive range of external rotation and increased strength may increase the risk of lower limb stress fracture and patellofemoral pain. Weaker hip external rotators and stronger hip abductors were found to significantly increase the risk of developing patellofemoral pain. Greater range of hip external rotation was also found to be a factor in increasing the risk of lower limb stress fracture however the figure is too small to be considered a clinically worthwhile effect. Although hip strength and hip range of motion were found to be risk factors for lower limb injury, no prospective study investigating the relationship between femoral torsion and lower limb injury was found. Therefore, one of the aims of this thesis was to provide preliminary data to uncover this relationship. Another aim of the work presented in this thesis was to develop a new ultrasound imaging protocol to assess femoral shaft torsion utilising a new landmark on the greater trochanter, ‘the ridge’. The protocol showed excellent intra-rater reliability (ICC2,1 = 0.98; 95% CI 0.97 to 0.99), and inter-rater reliability (ICC2,1 = 0.97; 95% CI 0.95 to 0.98). Fifty per cent of the measurements were within 1o both within and between raters and within 2.7o for 80% of the measurements. The largest difference between raters was 9.3o. Standard error of measurement (SEM) was 0.5 degrees and 0.6 degrees respectively for intra-rater and inter-rater reliability measurements. The excellent reliability supports its usage in the clinical setting. This work is presented in chapter 3. Consequently, using the newly developed reliable method, the relationship between femoral torsion and hip proprioception was examined in healthy adults (n=40). Hip proprioceptive acuity was measured using an active reproduction of movement in three different angles; 10% of neutral, 50% or mid-range and 90% of maximum external rotation. Greater range of medial shaft torsion was found to be associated with better hip proprioceptive acuity only at the angle near the end of maximum external rotation (r=-0.325, p=0.04) not at 10% (r=0.019, p=0.909) and 50% (r=0.116, p=0.478). The detail of this study is described in chapter 4 of this thesis. A cross-sectional study investigated the relationship between femoral shaft torsion and lower limb injury in dancers (n=80). No difference was found in the magnitude of femoral shaft torsion between injured and non-injured dancers (p = 0.94). The relationship between femoral shaft torsion and eight other hip measures was also investigated. Femoral shaft torsion was found to have a very weak, negative correlation with range of hip external rotation (r = -0.034, p=0.384) and turnout (r = -0.066, p=0.558). The association between femoral shaft torsion with all other variables was also found to be very weak. This study is described in detail in Chapter 5. Overall the results of the studies documented in this thesis: describe the development of a novel femoral torsion measurement tool, identify femoral shaft torsion as a measurable component of femoral torsion, and provide preliminary data and inferences regarding the relationship between femoral torsion, distal lower limb injury and lower limb proprioceptive acuity in a high risk population of dancers. It is proposed that future research will determine the extent to which femoral torsion poses a lower limb injury risk, which will inform the modification of screening protocols. The findings of this thesis will also assist clinicians to direct their prophylactic management to joints and soft tissues at risk. If a time-frame for development of FT can be identified, modified training loads may be investigated to enhance optimal FT and determine whether this minimises injury risk. This new information therefore will also provide a basis for future research that would likely be in longitudinal studies establishing relationships, hence providing useful information for coaches and clinicians regarding designing alternative methods of training in preventing lower limb injuries. The body of knowledge provided by this thesis will also inform researchers in determining the measures of the hip to be used in future research which might be worthwhile investigating in relation to lower limb injury

Structural failure and fracture of immature bone

Radiological features alone do not allow the discrimination between accidental paediatric long bone fractures or those caused by child abuse. Therefore, for those cases where the child is unable to communicate coherently, there is a clinical need to elucidate the mechanisms behind each fracture to provide a forensic biomechanical tool for clinical implementation. 5 months old ovine femurs and tibiae were used as surrogates for paediatric specimens and were subjected to micro-CT scans to obtain their geometrical and material properties. A novel methodology to align long bones so that they would be loaded in a state of pure bending and torsion was developed and compared against the use of a standard anatomical coordinate system. The second moment of area and its coefficient of variation (COV) for each alignment method were calculated to ascertain the reference axes that minimised the effect of eccentric loading. Wilcoxon-signed rank test showed a significant reduction in COV of the second moment of area using this new method, indicating that the bone has a more regular cross-section when this methodology is implemented. The algorithm generated the locations of subject-specific landmarks that can be used as a reference to align the bones in experimental testing. A low-cost platform that synchronized the data acquisition from the tensile testing machine and the strain gauges was built and used with a high speed camera to capture the fracture pattern in four-point bending at three strain rates and in torsion at two different strain rates, following commonly reported case histories. Finite element (FE) models of ovine tibiae in their optimised alignment were generated to replicate the fracture patterns that were obtained. Fracture initiation and propagation was simulated through the use of element deletion with a maximum principal strain criterion. The experiments produced transverse, oblique, and spiral fractures consistently, which were correlated with the finite element analysis, demonstrating the ability of this pipeline to now be adapted for use in forensic analysis.Open Acces

Interlandmark measurements from lodox statscan images with application to femoral neck anteversion assessment

Includes abstract.Includes bibliographical references.Clinicians often take measurements between anatomical landmarks on X-ray radiographs for diagnosis and treatment planning, for example in orthopaedics and orthodontics. X-ray images, however, overlap three-dimensional internal structures onto a two-dimensional plane during image formation. Depth information is therefore lost and measurements do not truly reflect spatial relationships. The main aim of this study was to develop an inter-landmark measurement tool for the Lodox Statscan digital radiography system. X-ray stereophotogrammetry was applied to Statscan images to enable three-dimensional point localization for inter-landmark measurement using two-dimensional radiographs. This technique requires images of the anatomical region of interest to be acquired from different perspectives as well as a suitable calibration tool to map image coordinates to real world coordinates. The Statscan is suited to the technique because it is capable of axial rotations for multiview imaging. Three-dimensional coordinate reconstruction and inter-landmark measurements were taken using a planar object and a dry pelvis specimen in order to assess the intra-observer measurement accuracy, reliability and precision. The system yielded average (X, Y, Z) coordinate reconstruction accuracy of (0.08 0.12 0.34) mm and resultant coordinate reconstruction accuracy within 0.4mm (range 0.3mm – 0.6mm). Inter-landmark measurements within 2mm for lengths and 1.80 for angles were obtained, with average accuracies of 0.4mm (range 0.0mm – 2.0 mm) and 0.30 (range 0.0 – 1.8)0 respectively. The results also showed excellent overall precision of (0.5mm, 0.10) and were highly reliable when all landmarks were completely visible in both images. Femoral neck anteversion measurement on Statscan images was also explored using 30 dry right adult femurs. This was done in order to assess the feasibility of the algorithm for a clinical application. For this investigation, four methods were tested to determine the optimal landmarks for measurement and the measurement process involved calculation of virtual landmarks. The method that yielded the best results produced all measurements within 10 of reference values and the measurements were highly reliable with very good precision within 0.10. The average accuracy was within 0.40 (range 0.10 –0.80).In conclusion, X-ray stereophotogrammetry enables accurate, reliable and precise inter-landmark measurements for the Lodox Statscan X-ray imaging system. The machine may therefore be used as an inter-landmark measurement tool for routine clinical applications

Impact of Ear Occlusion on In-Ear Sounds Generated by Intra-oral Behaviors

We conducted a case study with one volunteer and a recording setup to detect sounds induced by the actions: jaw clenching, tooth grinding, reading, eating, and drinking. The setup consisted of two in-ear microphones, where the left ear was semi-occluded with a commercially available earpiece and the right ear was occluded with a mouldable silicon ear piece. Investigations in the time and frequency domains demonstrated that for behaviors such as eating, tooth grinding, and reading, sounds could be recorded with both sensors. For jaw clenching, however, occluding the ear with a mouldable piece was necessary to enable its detection. This can be attributed to the fact that the mouldable ear piece sealed the ear canal and isolated it from the environment, resulting in a detectable change in pressure. In conclusion, our work suggests that detecting behaviors such as eating, grinding, reading with a semi-occluded ear is possible, whereas, behaviors such as clenching require the complete occlusion of the ear if the activity should be easily detectable. Nevertheless, the latter approach may limit real-world applicability because it hinders the hearing capabilities.</p

Medical robots for MRI guided diagnosis and therapy

Magnetic Resonance Imaging (MRI) provides the capability of imaging tissue with fine resolution and superior soft tissue contrast, when compared with conventional ultrasound and CT imaging, which makes it an important tool for clinicians to perform more accurate diagnosis and image guided therapy. Medical robotic devices combining the high resolution anatomical images with real-time navigation, are ideal for precise and repeatable interventions. Despite these advantages, the MR environment imposes constraints on mechatronic devices operating within it. This thesis presents a study on the design and development of robotic systems for particular MR interventions, in which the issue of testing the MR compatibility of mechatronic components, actuation control, kinematics and workspace analysis, and mechanical and electrical design of the robot have been investigated. Two types of robotic systems have therefore been developed and evaluated along the above aspects. (i) A device for MR guided transrectal prostate biopsy: The system was designed from components which are proven to be MR compatible, actuated by pneumatic motors and ultrasonic motors, and tracked by optical position sensors and ducial markers. Clinical trials have been performed with the device on three patients, and the results reported have demonstrated its capability to perform needle positioning under MR guidance, with a procedure time of around 40mins and with no compromised image quality, which achieved our system speci cations. (ii) Limb positioning devices to facilitate the magic angle effect for diagnosis of tendinous injuries: Two systems were designed particularly for lower and upper limb positioning, which are actuated and tracked by the similar methods as the first device. A group of volunteers were recruited to conduct tests to verify the functionality of the systems. The results demonstrate the clear enhancement of the image quality with an increase in signal intensity up to 24 times in the tendon tissue caused by the magic angle effect, showing the feasibility of the proposed devices to be applied in clinical diagnosis

Characterisation of disuse-related osteoporosis in an animal model of spinal cord injury

Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected.Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected