Identifying vertebral end plate lesions (schmorl's nodes) using a semi-automatic method

INTRODUCTION There is a large range in the reported prevalence of end plate lesions (EPLs), sometimes referred to as Schmorl's nodes in the general population (3.8-76%). One possible reason for this large range is the differences in definitions used by authors. Previous research has suggested that EPLs may potentially be a primary disturbance of growth plates that leads to the onset of scoliosis. The aim of this study was to develop a technique to measure the size, prevalence and location of EPLs on Computed Tomography (CT) images of scoliosis patients in a consistent manner. METHODS A detection algorithm was developed and applied to measure EPLs for five adolescent females with idiopathic scoliosis (average age 15.1 years, average major Cobb 60°). In this algorithm, the EPL definition was based on the lesion depth, the distance from the edge of the vertebral body and the gradient of the lesion edge. Existing low-dose, CT scans of the patients' spines were segmented semi-automatically to extract 3D vertebral endplate morphology. Manual sectioning of any attachments between posterior elements of adjacent vertebrae and, if necessary, endplates was carried out before the automatic algorithm was used to determine the presence and position of EPLs. RESULTS EPLs were identified in 15 of the 170 (8.8%) endplates analysed with an average depth of 3.1mm. 73% of the EPLs were seen in the lumbar spines (11/15). A sensitivity study demonstrated that the algorithm was most sensitive to changes in the minimum gradient required at the lesion edge. CONCLUSION An imaging analysis technique for consistent measurement of the prevalence, location and size of EPLs on CT images has been developed. Although the technique was tested on scoliosis patients, it can be used to analyse other populations without observer errors in EPL definitions.

Morphometric analysis of the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis using low dose computerized tomography

Introduction. The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). Methods. In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. Results. The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). Conclusion. Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Using axially loaded MRI to investigate the biomechanics of adolescent idiopathic scoliosis

Introduction. Spinal flexibility measurement is an important aspect of pre-operative clinical assessment in the treatment of Adolescent Idiopathic Scoliosis (AIS). Clinically, curve flexibility is a combined measure for all vertebral levels. We propose that in vivo flexibility for individual spinal joints could provide valuable additional information in planning treatment for scoliosis. Methods. Individual spinal joint flexibility in the coronal plane was measured for a series of AIS patients using axially loaded magnetic resonance imaging. Each patient underwent magnetic resonance imaging in the supine position, with no axial load, and then following application of an axial compressive load equal to half the patient’s bodyweight. Coronal plane disc wedge angles in the unloaded and loaded configurations were measured. Joint moments exerted by the axial compressive load were used to derive estimates of individual joint compliance. Results. Fifteen AIS patients were included in the study (mean clinical Cobb angle 46 degrees, mean age 15.3 years). Mean intra-observer measurement error for endplate inclination was 1.6˚. The mean increase in measured major Cobb angle between unloaded and loaded scans was 7.6˚. For certain spinal levels (+2,+1,-2 relative to the apex) there was a statistically significant relationship between change in wedge angle under load and initial wedge angle, such that initially highly wedged discs demonstrated a smaller change in wedge angle than less wedged discs. Highly wedged discs were observed near the apex of the curve, which corresponded to lower joint compliance in the apical region. Conclusion. Approaches such as this can provide valuable biomechanical data on in vivo spinal biomechanics in AIS. Knowledge of individual joint flexibility may assist surgeons to determine which spinal procedure is most appropriate for a patient, which levels should be included in a spinal fusion and the relative mobility of individual joints in the deformed region of the spine.

Using low dose computerized tomography to morphometrically analyse the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis

INTRODUCTION The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). METHODS In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. RESULTS The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). CONCLUSION Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Sequential MRI of growing scoliotic spines reveals individual level deformities that are clinically masked by the cobb angle

INTRODUCTION. Clinically, the Cobb angle method measures the overall scoliotic curve in the coronal plane but does not measure individual vertebra and disc wedging. The contributions of the vertebrae and discs in the growing scoliotic spine were measured to investigate coronal plane deformity progression with growth. METHODS. A 0.49mm isotropic 3D MRI technique was developed to investigate the level-by-level changes that occur in the growing spine of a group of Adolescent Idiopathic Scoliosis (AIS) patients, who received two to four sequential scans (spaced 3-12 months apart). The coronal plane wedge angles of each vertebra and disc in the major curve were measured to capture any changes that occurred during their adolescent growth phase. RESULTS. Seventeen patients had at least two scans. Mean patient age was 12.9 years (SD 1.5 years). Sixteen were classified as right-sided major thoracic Lenke Type 1 (one left sided). Mean standing Cobb angle at initial presentation was 31° (SD 12°). Six received two scans, nine three scans and two four scans, with 65% showing a Cobb angle progression of 5° or more between scans. Overall, there was no clear pattern of deformity progression of individual vertebrae and discs, nor between patients who progressed and those who didn’t. There were measurable changes in the wedging of the vertebrae and discs in all patients. In sequential scans, change in direction of wedging was also seen. In several patients there was reverse wedging in the discs that counteracted increased wedging of the vertebrae such that no change in overall Cobb angle was seen. CONCLUSION. Sequential MRI data showed complex patterns of deformity progression. Changes to the wedging of individual vertebrae and discs may occur in patients who have no increase in Cobb angle measure; the Cobb method alone may be insufficient to capture the complex mechanisms of deformity progression.

On the biomechanical significance of inter-lamellar interfaces in the intervertebral disc

The intervertebral disc (IVD) is a unique soft tissue structure which provides structural support and flexibility in the axial skeleton of vertebrates. From a structural perspective, the disc behaves somewhat like a thick walled pressure vessel, where the walls are comprised of a series of composite annular rings (lamellae). However, a prior study (Marchand and Ahmed, 1990) found a high proportion of circumferentially discontinuous lamellae in human lumbar IVDs. The presence of these discontinuities raises important structural questions, because discontinuous lamellae cannot withstand high nucleus pressures via the generation of circumferential (hoop) stress. A possible alternative mechanism may be that inter-lamellar cohesion allows shear stress transfer between adjacent annular layers. The aim of the present study was therefore to investigate the importance of inter-lamellar shear resistance in the intervertebral disc. This work found that inter-lamellar shear resistance has a strong influence on the compressive stiffness of the intervertebral disc, with a change in interface condition from tied (no slip) to frictionless (no shear resistance) reducing disc compressive stiffness by 40%. However, it appears that substantial inter-lamellar shear resistance is present in the bovine tail disc. Decreases in inter-lamellar shear resistance due to degradation of bridging collagenous or elastic fibre structures could therefore be an important part of the process of disc degeneration.

Multimodal imaging of the collagen and elastic fibre networks in the bovine intervertebral disc

INTRODUCTION. The intervertebral disc is the largest avascular structure in the human body, withstanding transient loads of up to nine times body weight during rigorous physical activity. The key structural elements of the disc are a gel-like nucleus pulposus surrounded by concentric lamellar rings containing criss-crossed collagen fibres. The disc also contains an elastic fiber network which has been suggested to play a structural role, but to date the relationship between the collagen and elastic fiber networks is unclear. CONCLUSION. The multimodal transmitted and reflected polarized light microscopy technique developed here allows clear differentiation between the collagen and elastic fiber networks of the intervertebral disc. The ability to image unstained specimens avoids concerns with uneven stain penetration or specificity of staining. In bovine tail discs, the elastic fiber network is intimately associated with the collagen network.

Supine to standing cobb angle change in idiopathic scoliosis: The effect of endplate preselection

INTRODUCTION Standing radiographs are the ‘gold standard’ for clinical assessment of adolescent idiopathic scoliosis (AIS), with the Cobb Angle used to measure the severity and progression of the scoliotic curve. Supine imaging modalities can provide valuable 3D information on scoliotic anatomy, however, due to changes in gravitational loading direction, the geometry of the spine alters between the supine and standing position which in turn affects the Cobb Angle measurement. Previous studies have consistently reported a 7-10° [1-3] Cobb Angle increase from supine to standing, however, none have reported the effect of endplate pre-selection and which (if any) curve parameters affect the supine to standing Cobb Angle difference. CONCLUSION There is a statistically significant relationship between supine to standing Cobb Angle change and fulcrum flexibility. Therefore, this difference can be considered a measure of spinal flexibility. Pre-selecting vertebral endplates causes only minor changes.

Predicting surgical outcomes for paediatric spinal deformity patients using subject specific finite element models

INTRODUCTION Adolescent idiopathic scoliosis (AIS) is a spinal deformity, which may require surgical correction by attaching rods to the patient’s spine using screws inserted into the vertebrae. Complication rates for deformity correction surgery are unacceptably high. Determining an achievable correction without overloading the adjacent spinal tissues or implants requires an understanding of the mechanical interaction between these components. Our novel patient specific modelling software creates individualized finite element models (FEM) representing the thoracolumbar spine and ribcage of scoliosis patients. We have recently applied the model to investigate the influence of increasing magnitudes of surgically applied corrective force on predicted deformity correction...

Sequential MRI reveals individual level deformities in the growing scoliotic spine that are not seen clinically by the cobb angle

Clinically, the Cobb angle method measures the overall scoliotic curve in the coronal plane but does not measure individual vertebra and disc wedging. The contributions of the vertebrae and discs in the growing scoliotic spine were measured to investigate coronal plane deformity progression with growth. Sequential MRI data in this project showed complex patterns of deformity progression. Changes to the wedging of individual vertebrae and discs may occur in patients who have no increase in Cobb angle measure; the Cobb method alone may be insufficient to capture the complex mechanisms of deformity progression.

Using the factors that have a positive impact on the retention of low socioeconomic students to prepare accelerated enrolled nurses for the science units of a nursing degree : a practice report

At a campus in a low socioeconomic (SES) area, our University allows enrolled nurses entry into the second year of a Bachelor of Nursing, but attrition is high. Using the factors, described by Yorke and Thomas (2003) to have a positive impact on the attrition of low SES students, we developed strategies to prepare the enrolled nurses for the pharmacology and bioscience units of a nursing degree with the aim of reducing their attrition. As a strategy, the introduction of review lectures of anatomy, physiology and microbiology, was associated with significantly reduced attrition rates. The subsequent introduction of a formative website activity of some basic concepts in bioscience and pharmacology, and a workshop addressing study skills and online resources, were associated with a further reduction in attrition rates of enrolled nursing students in a Bachelor of Nursing.

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features

Objective National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated Methods A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. Results The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients). Conclusions Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome

Interleukin 17A is an immune marker for chlamydial disease severity and pathogenesis in the koala (Phascolarctos cinereus)

The koala (Phascolarctos cinereus) is an iconic Australian marsupial species that is facing many threats to its survival. Chlamydia pecorum infections are a significant contributor to this ongoing decline. A major limiting factor in our ability to manage and control chlamydial disease in koalas is a limited understanding of the koala’s cell-mediated immune response to infections by this bacterial pathogen. To identify immunological markers associated with chlamydial infection and disease in koalas, we used koala-specific Quantitative Real Time PCR (qrtPCR) assays to profile the cytokine responses of Peripheral Blood Mononuclear Cells (PBMCs) collected from 41 koalas with different stages of chlamydial disease. Target cytokines included the principal Th1 (Interferon gamma; IFNγ), Th2 (Interleukin 10; IL10), and pro-inflammatory cytokines (Tumor Necrosis Factor alpha; TNFα). A novel koala-specific IL17A qrtPCR assay was also developed as part of this study to quantitate the gene expression of this Th17 cytokine in koalas. A statistically significant higher IL17A gene expression was observed in animals with current chlamydial disease compared to animals with asymptomatic chlamydial infection. A modest up-regulation of pro-inflammatory cytokines, such as TNFα and IFNγ, was also observed in these animals with signs of current chlamydial disease. IL10 gene expression was not evident in the majority of animals from both groups. Future longitudinal studies are now required to confirm the role played by cytokines in pathology and/or protection against C. pecorum infection in the koala.

Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses

Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime.

Molecular and pathological insights into Chlamydia pecorum-associated sporadic bovine encephalomyelitis (SBE) in Western Australia

Background Despite its global recognition as a ruminant pathogen, cases of Chlamydia pecorum infection in Australian livestock are poorly documented. In this report, a C. pecorum specific Multi Locus Sequence Analysis scheme was used to characterise the C. pecorum strains implicated in two cases of sporadic bovine encephalomyelitis confirmed by necropsy, histopathology and immunohistochemistry. This report provides the first molecular evidence for the presence of mixed infections of C. pecorum strains in Australian cattle. Case presentation Affected animals were two markedly depressed, dehydrated and blind calves, 12 and 16 weeks old. The calves were euthanized and necropsied. In one calf, a severe fibrinous polyserositis was noted with excess joint fluid in all joints whereas in the other, no significant lesions were seen. No gross abnormalities were noted in the brain of either calf. Histopathological lesions seen in both calves included: multifocal, severe, subacute meningoencephalitis with vasculitis, fibrinocellular thrombosis and malacia; diffuse, mild, acute interstitial pneumonia; and diffuse, subacute epicarditis, severe in the calf with gross serositis. Immunohistochemical labelling of chlamydial antigen in brain, spleen and lung from the two affected calves and brain from two archived cases, localised the antigen to the cytoplasm of endothelium, mesothelium and macrophages. C. pecorum specific qPCR, showed dissemination of the pathogen to multiple organs. Phylogenetic comparisons with other C. pecorum bovine strains from Australia, Europe and the USA revealed the presence of two genetically distinct sequence types (ST). The predominant ST detected in the brain, heart, lung and liver of both calves was identical to the C. pecorum ST previously described in cases of SBE. A second ST detected in an ileal tissue sample from one of the calves, clustered with previously typed faecal bovine isolates. Conclusion This report provides the first data to suggest that identical C. pecorum STs may be associated with SBE in geographically separated countries and that these may be distinct from those found in the gastrointestinal tract. This report provides a platform for further investigations into SBE and for understanding the genetic relationships that exist between C. pecorum strains detected in association with other infectious diseases in livestock.