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Overloading of the back can cause instability such that buttressing the instability is a primary objective of many of the leading edge therapeutic approaches. However, a challenge lies in determining the location of the instability or the least stable vertebral joint. A mathematical analysis, based on a commonly used approach in engineering for determining structural stability, has been developed for the lumbar spine. The purpose of this investigation was to determine the feasibility of a method for mathematically locating potential areas of instability within a computer-based model of the lumbar spine. To validate this method, the eigenvector from the stability analysis was compared to the output from a geometric equation that approximated individual vertebral joint rotational stiffness with the idea that the entry in the eigenvector with the largest absolute value would correspond to the vertebral joint and axis with the lowest stiffness. Validation of the eigenvector was not possible due to computational similarities between the stability analysis and the geometric rotational stiffness method. However, it has been previously demonstrated that the eigenvector can be useful for locating instability, and thus warrants future study. Determining the least stable vertebral joint and axis can be used to guide proper motor pattern training as a clinical intervention. It was also shown in this investigation that an even distribution of fascicle force and stiffness generated stability. This supports the idea that well-coordinated efforts of muscle activation are beneficial for improving stability of the lumbar spine.

Low back pain is highly prevalent in the developed world, with 80% of the population being affected at some point in their lives. Herniation, a common injury to the intervertebral disc, is characterized as the posterior migration of the nucleus pulposus through the layers of the annulus fibrosus. Various risk factors have been associated with the development of disc herniation, but the mechanisms are largely not understood. For example, exposure to vibration has been linked to the occurrence of herniation, yet our understanding of this association is not clear. It is hypothesized that vibration cyclically loads the tissues of the intervertebral disc until failure occurs as a result of fatigue. Tissues at risk of fatigue failure may include the intra-lamellar matrix, the connective tissue found between collagen fibres within a single lamella, and the inter-lamellar matrix, the connective tissue found between adjacent lamellae. In order to determine the mechanistic link between vibration and herniation, a firm understanding of the properties of the intervertebral disc as well as the intra and inter-lamellar matrices are of utmost importance. Further, it is important to determine these properties under physiological loading scenarios. This thesis consists of five studies, which have each provided a unique piece to the intervertebral disc herniation puzzle in order to better understand this mechanistic link. First, it was discovered that annular tissue is subject to significantly higher stresses and is stiffer under biaxial strain as compared to uniaxial strain. Biaxial strain is more representative of the in vivo loading scenario and provides more accurate information regarding scenarios that the annulus can tolerate and those that can result in injury. It was also revealed that, when strained at physiological strain rates (up to 4%/sec), these mechanical properties do not change such that they are independent of strain rate. Therefore, when strained at varying rates akin to voluntary movement, the annulus is not subject to higher stresses or altered stiffness. Second, the effect of vibration, an acknowledged risk factor for herniation, was examined on the mechanical properties of the intra and inter-lamellar matrices. It was discovered that vibration altered these matrices such that they were more extensible and strained to greater magnitudes, yet did not reach higher stresses before failing. It was hypothesized that this increased extensibility was due to damage to elastin, as elastin assists in minimizing tissue deformation and helps tissues recover from tensile strain. The final study assessed the effect of exposure to vibration on the development of disc herniation. The initiation of herniation was observed in a significantly greater number of intervertebral discs exposed to vibration as compared to a control condition. Although epidemiological studies had documented a correlation between exposure to vibration and herniation, this was the first study to conclude that exposure to vibration is in fact a mechanical risk factor for the development of herniation and increases the incidence of herniation. Further, based on the findings of the mechanical properties of the intra and inter-lamellar matrices, and in particular the observed 15-20 times greater failure strength of the intra as compared to inter-lamellar matrix, it would appear that the inter-lamellar matrix, and thus delamination, may be the weakest link in the herniation pathway. This thesis has uncovered new information regarding physiological mechanical properties of the annulus. Further, new information regarding the intra and inter-lamellar matrices was obtained, improving our understanding of the healthy disc. Last, by subjecting the disc to a known risk factor for herniation, hypotheses were generated regarding the initiation and progression of disc herniation, specifically related to the roles of the intra and inter-lamellar matrices.

General body discomfort increases over time during prolonged sitting and it is typically accepted that no single posture can be comfortably maintained for long periods. Despite this knowledge, workplace exposure to prolonged sitting is very common. Sedentary occupations that expose workers to prolonged sitting are associated with an increased risk of developing low back pain (LBP), disc degeneration and lumbar disc herniation. Given the prevalence of occupations with a large amount of seated work and the propensity for a dose-response relationship between sitting and LBP, refining our understanding of the biomechanics of the lumbar spine during sitting is important. Sitting imposes a flexed posture that, when held for a prolonged period of time, may cause detrimental effects on the tissues of the spine. While sitting is typically viewed as a sedentary and constrained task, several researchers have identified the importance of investigating movement during prolonged sitting. The studies in this thesis were designed to address the following two global questions: (1) How do the lumbar spine and pelvis move during sitting? (2) Can lumbar spine movement and postures explain LBP and injury associated with prolonged sitting? The first study (Study 1) examined static X-ray images of the lower lumbo-sacral spine in a range of standing and seated postures to measure the intervertebral joint angles that contribute to spine flexion. The main finding was that the lower lumbo-sacral joints approach their total range of motion in seated postures. This suggests that there could be increased loading of the passive tissues surrounding the lower lumbo-sacral intervertebral joints, contributing to low back pain and/or injury from prolonged sitting. Study 2 compared external spine angles measured using accelerometers from L3 to the sacrum with corresponding angles measured from X-ray images. While the external and internal angles did not match, the accelerometers were sensitive to changes in seated lumbar posture and were consistent with measurements made using similar technology in other studies. This study also provided an in-depth analysis of the current methods for data treatment and how these methods affect the outcomes. A further study (Study 3) employed videofluoroscopy to investigate the dynamic rotational kinematics of the intervertebral joints of the lumbo-sacral spine in a seated slouching motion in order to determine a sequence of vertebral motion. The pelvis did not initiate the slouching motion and a disordered sequence of vertebral rotation was observed at the initiation of the movement. Individuals performed the slouching movement using a number of different motion strategies that influenced the IVJ angles attained during the slouching motion. From the results of Study 1, it would appear as though the lowest lumbar intervertebral joint (L5/S1) contribute the most to lumbo-sacral flexion in upright sitting, as it is at approximately 60% of its end range in this posture. However, the results from Study 3 suggest that there is no consistent sequence of intervertebral joint rotation when flexing the spine from upright to slouched sitting. When moving from standing to sitting, lumbar spine flexion primarily occurs at the lowest joint (i.e. L5/S1); however, a disordered sequence of vertebral motion the different motion patterns observed may indicate that different joints approach their end range before the completion of the slouching movement. In order to understand the biomechanical factors associated with sitting induced low back pain, Study 4 examined the postural responses and pain scores of low back pain sufferers compared with asymptomatic individuals during prolonged seated work. The distinguishing factor between these two groups was their respective time-varying seated lumbar spine movement patterns. Low back pain sufferers moved more than asymptomatic individuals did during 90 minutes of seated work and they reported increased low back pain over time. Frequent shifts in lumbar spine posture could be a mechanism for redistributing the load to different tissues of the spine, particularly if some tissues are more vulnerable than others. However, increased movement did not completely eliminate pain in individuals with pre-existing LBP. The LBP sufferers’ seated spine movements increased in frequency and amplitude as time passed. It is likely that these movements became more difficult to properly control because LBP patients may lack proper lumbar spine postural control. The results of this study highlight the fact that short duration investigations of seated postures do not accurately represent the biological responses to prolonged exposure. Individuals with sitting-induced low back pain and those without pain differ in how they move during seated work and this will have different impacts on the tissues of the lumbar spine. A tissue-based rational for the detrimental effects on the spinal joint of prolonged sitting was examined in Study 5 using an in vitro spine model and simulated spine motion patterns documented in vivo from Study 4. The static protocol simulated 2 hours of sitting in one posture. The shift protocol simulated infrequent but large changes in posture, similar to the seated movements observed in a group of LBP sufferers. The fidget protocol replicated small, frequent movements about one posture, demonstrated by a group of asymptomatic individuals. Regardless of the amount of spine movement around one posture, all specimens lost a substantial amount of disc height. Furthermore, the passive range of motion of a joint changed substantially after 2 hours of simulated sitting. Specifically, there were step-like regions of reduced stiffness throughout the passive range of motion particularly around the adopted “seated flexion” angle. However, small movements around a posture (i.e. fidgeting) may mitigate the changes in the passive stiffness in around the seated flexion angle. The load transferred through the joint during the 2-hour test was varied either by changing postures (i.e. shifting) or by a potential creep mechanism (i.e. maintaining one static posture). Fidgeting appeared to reduce the variation of load carriage through the joint and may lead to a more uniform increase in stiffness across the entire passive range of motion. These changes in passive joint mechanics could have greater consequences for a low back pain population who may be more susceptible to abnormal muscular control and clinical instability. Nevertheless, the observed disc height loss and changes in joint mechanics may help explain the increased risk of developing disc herniation and degeneration if exposure to sitting is cumulative over many days, months and years. In summary, this work has highlighted that seated postures place the joints of the lumbar spine towards their end range of motion, which is considered to be risky for pain/injury in a number of tissue sources. In-depth analyses of both internal and external measurements of spine postures identified different seated motion patterns and self-selected seated postures that may increase the risk for developing LBP. The model of seated LBP/discomfort development used in this thesis provided evidence that large lumbar spine movements do not reduce pain in individuals with pre-existing LBP. Tissue-based evidence demonstrated that 2 hours of sitting substantially affects IVJ mechanics and may help explain the increased risk of developing disc herniation and degeneration if exposure to sitting is cumulative over many days, months and years. The information obtained from this thesis will help develop and refine interventions in the workplace to help reduce low back pain during seated work.

The purpose of this study is to quantify the dynamic mechanical properties of human cervical ligaments following whiplash. Cervical ligaments function to provide spinal stability, propioception, and protection during traumatic events to the spine. The function of cervical ligaments is largely dependant on their dynamic biomechanical properties, which include force and energy resistance, elongation capability, and stiffness. Whiplash has been shown to injure human cervical spine ligaments, and ligamental injury has been shown to alter their dynamic properties, with potential clinical consequences such as joint degeneration and pain. In this study we quantified the dynamic properties of human lower cervical ligaments following whiplash and compared their properties to those of intact ligaments. Whiplash simulation was performed using biofidelic whole cervical spine with muscle force replication (WCS-MFR) models. Next, ligaments were elongated to failure at a fast elongation rate and peak force, peak elongation, peak energy, and stiffness values were calculated from non-linear force-elongation curves. Peak force was highest in the ligamentum flavum (LF) and lowest in the intraspinous and supraspinous ligaments (ISL+SSL). Elongation was smallest in middle-third disc (MTD) and greatest in ISL+SSL. Highest peak energy was found in capsular ligament (CL) and lowest in MTD. LF was the stiffest ligament and ISL+SSL least stiff. These findings were similar to those found in intact ligaments. When directly comparing ligaments following whiplash to intact ligaments in a prior study it was found that the anterior longitudinal ligament (ALL) and CL had altered dynamic properties that were statistically significant, suggesting that whiplash may alter the dynamic properties of cervical ligaments. These findings may contribute to the understanding of whiplash injuries and the development of mathematical models simulating spinal injury.

Despite the importance of proper synaptogenesis in the CNS, the molecular mechanisms that regulate the formation and development of synapses remain poorly understood. Indeed, the mechanisms through which initial synaptic contacts are established and modified during synaptogenesis have not been fully determined and a precise understanding of these mechanisms may shed light on synaptic development, plasticity and many CNS developmental diseases. The development and formation of spiny synapses has been thought to occur via filopodia shortening followed by the recruitment of proper postsynaptic proteins, however the precise function of filopodia remains controversial. Thus the goal of this study was to investigate the dynamics of dendritic filopodia and determine their role in the development of synaptic contacts. We initially define and characterize short lipidated motifs that are sufficient to induce process outgrowth. Indeed, the palmitoylated protein motifs of GAP-43 and paralemmin are sufficient to induce filopodial extensions in heterologous cells and to increase the number of filopodia and dendritic branches in neurons. We showed that the morphological changes induced by these FIMs (filopodia inducing motifs) require on-going protein palmitoylation and are modulated by a specific GTPase, Cdc42, that regulates actin dynamics. We also show that their function is palmitoylation dependent and is dynamically regulated by reversible protein palmitoylation. Significantly, our work suggests a general role for those palmitoylated motifs in the development of structures important for synapse formation and maturation. We combined several approaches to monitor the formation and development of filopodia. We show that filopodia continuously explore the environment and probe for appropriate contacts with presynaptic partners. We find that shortly after establishing a contact with axons, filopodia induce the recruitment of presynaptic elements. Remarkably, we find that expression of acylated motifs or the constitutively active form of cdc-42 enhances filopodia number and motility, but reduces the recruitment of synaptophysin positive presynaptic elements and the probability of forming stable axo-dendritic contacts. We provide evidence for the rapid transformation of filopodia to spines within hours of imaging live neurons and reveal potential molecules that accelerate this process.

Multi-echo T2 relaxation measurements of the human spinal cord (SC) reveal a short T2 pool of water believed to arise from water trapped between myelin bilayers, where the proportion of this water to the total water signal is called the myelin water fraction (MWF). In the present study, MWF were measured in the healthy human cervical spine at the C4-C6 vertebral levels in vivo using a 3D modified 32 echo CPMG sequence to acquire axial slices perpendicular to the cord. Volunteers were recruited in two age ranges, under 30 years old and over 50 years old, and a subset of both groups were scanned twice to test reproducibility. Mean MWF in the dorsal and lateral column WM of the group under 30 years of age was 0.29 (0.01) (mean(SE)), which agrees with previously reported MWF values in the cervical spine. The mean absolute difference between two scans was 0.06 or 26%. A negative correlation between WM MWF and age was hinted at in these findings, however more subjects are required to improve statistical power. This study paves the way for the use of 3D myelin water imaging in the cervical spine at 3.0T for the assessment of SC WM pathology.

Spinal injections for back-pain management are frequently carried out in hospitals and radiological clinics. Currently, these procedures are performed under fluoroscopy or CT guidance in specialized interventional radiology facilities, and thus incur a major financial burden on the healthcare system. Additionally, the current practice exposes patients and surgeons to X-ray radiation. The use of US for image guided navigation of the spine would greatly reduce the exposure of both the patient and the physician to ionizing radiation and allow the procedure to be performed outside of a specialized facility. However, US as the sole guidance modality has its own challenges. In particular, due to the significant level of occlusion in spinal US images, it can be difficult to accurately identify the appropriate injection site. Here, a groupwise US to CT registration algorithm for guiding percutaneous spinal interventions is presented. In our registration methodology, each vertebra in CT is treated as a sub-volume and transformed individually. A biomechanical model is used to constrain the displacement of the vertebrae relative to one another. The sub-volumes are then reconstructed into a single volume. In each iteration of registration, an US image is simulated from the reconstructed CT volume and an intensity-based similarity metric with the real US image is calculated. Validation studies are performed on datasets from a lamb cadaver, five patient-based phantoms designed to preserve realistic curvatures of the spine and a sixth patient-based phantom where the curvature of the spine is changed between preoperative and intraoperative imaging. For datasets where the spine curve between two imaging modalities was artificially perturbed, the proposed methodology was able to register initial misalignments of up to 20 mm with a success rate of 95%. For the phantom with a physical change in the curvature of the spine introduced between the US and CT datasets, the registration success rate was 98.5%. Finally, the registration success rate for the lamb cadaver with soft tissue information was 87%. The results demonstrate that our algorithm robustly registers US and CT datasets of the spine, regardless of a change in the patients pose between preoperative and intraoperative image acquisitions. / Thesis (Master, Computing) -- Queen's University, 2009-11-27 13:48:33.288

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Scoliosis is defined as the abnormal three dimensional curvature of the spine with 80% of all cases being idiopathic in nature. If left unchecked, this condition can cause cardio-pulmonary complications and occasionally death. Currently, the most common method of treatment of scoliosis is through mechanical bracing or in extreme cases, corrective surgery. Current treatments can be further improved with a greater understand of the growth patterns of scoliotic spines. The objective of this study is to develop a finite element spine model capable of responding to loading conditions in a similar fashion to previous finite biomechanics spine model and utilize the ‘vicious cycle’ scoliosis theory in an effort to model scoliosis growth. Using CT images of a healthy spine, a three dimensional finite element model of the L3-L4 vertebra is generated. Asymmetric loading due to compression and muscle forces can then be applied on the spine and the resultant stresses are then translated into equivalent thermal load. Using this thermal load, it is possible to cause the spine model to grow, thereby predicting the growth pattern of a spine due to asymmetric loading.