Can the contra-lateral limb be used as a control with respect to analyses of bone remodelling?

Bone loss may result from remodelling initiated by implant stress protection. Quantifying remodelling requires bone density distributions which can be obtained from computed tomography scans. Pre-operative scans of large animals however are rarely possible. This study aimed to determine if the contra-lateral bone is a suitable control for the purpose of quantifying bone remodelling. CT scans of 8 pairs of ovine tibia were used to determine the likeness of left and right bones. The deviation between the outer surfaces of the bone pairs was used to quantify geometric similarity. The density differences were determined by dividing the bones into discrete volumes along the shaft of the tibia. Density differences were also determined for fractured and contra-lateral bone pairs to determine the magnitude of implant related remodelling. Left and right ovine tibiae were found to have a high degree of similarity with differences of less than 1.0 mm in the outer surface deviation and density difference of less than 5% in over 90% of the shaft region. The density differences (10–40%) as a result of implant related bone remodelling were greater than left-right differences. Therefore, for the purpose of quantifying bone remodelling in sheep, the contra-lateral tibia may be considered an alternative to a pre-operative control.

A biomechanical investigation of vertebral staples for fusionless scoliosis correction

Background: Fusionless scoliosis surgery is an early-stage treatment for idiopathic scoliosis which claims potential advantages over current fusion-based surgical procedures. Anterior vertebral stapling using a shape memory alloy staple is one such approach. Despite increasing interest in this technique, little is known about the effects on the spine following insertion, or the mechanism of action of the staple. The purpose of this study was to investigate the biomechanical consequences of staple insertion in the anterior thoracic spine, using in vitro experiments on an immature bovine model. Methods: Individual calf spine thoracic motion segments were tested in flexion, extension, lateral bending and axial rotation. Changes in motion segment rotational stiffness following staple insertion were measured on a series of 14 specimens. Strain gauges were attached to three of the staples in the series to measure forces transmitted through the staple during loading. A micro-CT scan of a single specimen was performed after loading to qualitatively examine damage to the vertebral bone caused by the staple. Findings: Small but statistically significant decreases in bending stiffness occurred in flexion,extension, lateral bending away from the staple, and axial rotation away from the staple. Each strain-gauged staple showed a baseline compressive loading following insertion which was seen to gradually decrease during testing. Post-test micro-CT showed substantial bone and growth plate damage near the staple. Interpretation: Based on our findings it is possible that growth modulation following staple insertion is due to tissue damage rather than sustained mechanical compression of the motion segment.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Influence of internal fixator stiffness on murine fracture healing : two types of fracture healing lead to two distinct cellular events and FGF-2 expressions

This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Protection of microgrids using differential relays

A microgrid provides economical and reliable power to customers by integrating distributed resources more effectively. Islanded operation enables a continuous power supply for loads during a major grid disturbance. Reliability of a microgrid can be further increased by forming a mesh configuration. However, the protection of mesh microgrids is a challenging task. In this paper, protection schemes are discussed using current differential protection of a microgrid. The protection challenges associated with bi-directional power flow, meshed configuration, changing fault current level due to intermittent nature of DGs and reduced fault current level in an islanded mode are considered in proposing the protection solutions. Relay setting criterion and current transformer (CT) selection guidelines are also discussed. The results are verified using MATLAB calculations and PSCAD simulations.

Technical note : a technique for measuring the surface area of articular cartilage in acetabular fractures

The aim of this study was to develop a reliable technique for measuring the area of a curved surface from an axial computed tomography (CT) scan and to apply this clinically in the measurement of articular cartilage surface area in acetabular fractures. The method used was a triangulation algorithm. In order to determine the accuracy of the technique, areas of hemispheres of known size were measured to give the percentage error in area measurement. Seven such hemispheres were machined into a Perspex block and their area measured geometrically, and also from CT scans by means of the triangulation algorithm. Scans of 1, 2 and 4 mm slice thickness and separation were used. The error varied with slice thickness and hemisphere diameter. It was shown that the 2 mm slice thickness provides the most accurate area measurement, while 1 mm cuts overestimate and 4 mm cuts underestimate the area. For a hemisphere diameter of 5 cm, which is of similar size to the acetabulum, the error was -11.2% for 4 mm cuts, +4.2% for 2 mm cuts and + 5.1% for 1 mm cuts. As expected, area measurement was more accurate for larger hemispheres. This method can be applied clinically to quantify acetabular fractures by measuring the percentage area of intact articular cartilage. In the case of both column fractures, the percentage area of secondary congruence can be determined. This technique of quantifying acetabular fractures has a potential clinical application as a prognostic factor and an indication for surgery in the long term.

Monte Carlo verification of gel dosimetry measurements for stereotactic radiotherapy

The quality assurance of stereotactic radiotherapy and radiosurgery treatments requires the use of small-field dose measurements that can be experimentally challenging. This study used Monte Carlo simulations to establish that PAGAT dosimetry gel can be used to provide accurate, high resolution, three-dimensional dose measurements of stereotactic radiotherapy fields. A small cylindrical container (4 cm height, 4.2 cm diameter) was filled with PAGAT gel, placed in the parietal region inside a CIRS head phantom, and irradiated with a 12 field stereotactic radiotherapy plan. The resulting three-dimensional dose measurement was read out using an optical CT scanner and compared with the treatment planning prediction of the dose delivered to the gel during the treatment. A BEAMnrc DOSXYZnrc simulation of this treatment was completed, to provide a standard against which the accuracy of the gel measurement could be gauged. The three dimensional dose distributions obtained from Monte Carlo and from the gel measurement were found to be in better agreement with each other than with the dose distribution provided by the treatment planning system's pencil beam calculation. Both sets of data showed close agreement with the treatment planning system's dose distribution through the centre of the irradiated volume and substantial disagreement with the treatment planning system at the penumbrae. The Monte Carlo calculations and gel measurements both indicated that the treated volume was up to 3 mm narrower, with steeper penumbrae and more variable out-of-field dose, than predicted by the treatment planning system. The Monte Carlo simulations allowed the accuracy of the PAGAT gel dosimeter to be verified in this case, allowing PAGAT gel to be utilised in the measurement of dose from stereotactic and other radiotherapy treatments, with greater confidence in the future.

Effects of surgical joint destabilization on load sharing between ligamentous structures in the thoracic spine : a finite element investigation

Background: In vitro investigations have demonstrated the importance of the ribcage in stabilising the thoracic spine. Surgical alterations of the ribcage may change load-sharing patterns in the thoracic spine. Computer models are used in this study to explore the effect of surgical disruption of the rib-vertebrae connections on ligament load-sharing in the thoracic spine. Methods: A finite element model of a T7-8 motion segment, including the T8 rib, was developed using CT-derived spinal anatomy for the Visible Woman. Both the intact motion segment and the motion segment with four successive stages of destabilization (discectomy and removal of right costovertebral joint, right costotransverse joint and left costovertebral joint) were analysed for a 2000Nmm moment in flexion/extension, lateral bending and axial rotation. Joint rotational moments were compared with existing in vitro data and a detailed investigation of the load sharing between the posterior ligaments carried out. Findings: The simulated motion segment demonstrated acceptable agreement with in vitro data at all stages of destabilization. Under lateral bending and axial rotation, the costovertebral joints were of critical importance in resisting applied moments. In comparison to the intact joint, anterior destabilization increases the total moment contributed by the posterior ligaments. Interpretation: Surgical removal of the costovertebral joints may lead to excessive rotational motion in a spinal joint, increasing the risk of overload and damage to the remaining ligaments. The findings of this study are particularly relevant for surgical procedures involving rib head resection, such as some techniques for scoliosis deformity correction.

Rule-based approach for identifying assertions in clinical free-text data

A rule-based approach for classifying previously identified medical concepts in the clinical free text into an assertion category is presented. There are six different categories of assertions for the task: Present, Absent, Possible, Conditional, Hypothetical and Not associated with the patient. The assertion classification algorithms were largely based on extending the popular NegEx and Context algorithms. In addition, a health based clinical terminology called SNOMED CT and other publicly available dictionaries were used to classify assertions, which did not fit the NegEx/Context model. The data for this task includes discharge summaries from Partners HealthCare and from Beth Israel Deaconess Medical Centre, as well as discharge summaries and progress notes from University of Pittsburgh Medical Centre. The set consists of 349 discharge reports, each with pairs of ground truth concept and assertion files for system development, and 477 reports for evaluation. The system’s performance on the evaluation data set was 0.83, 0.83 and 0.83 for recall, precision and F1-measure, respectively. Although the rule-based system shows promise, further improvements can be made by incorporating machine learning approaches.

A subject-specific model of human buttocks and thighs in a seated posture

Finite element analyses of the human body in seated postures requires digital models capable of providing accurate and precise prediction of the tissue-level response of the body in the seated posture. To achieve such models, the human anatomy must be represented with high fidelity. This information can readily be defined using medical imaging techniques such as Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). Current practices for constructing digital human models, based on the magnetic resonance (MR) images, in a lying down (supine) posture have reduced the error in the geometric representation of human anatomy relative to reconstructions based on data from cadaveric studies. Nonetheless, the significant differences between seated and supine postures in segment orientation, soft-tissue deformation and soft tissue strain create a need for data obtained in postures more similar to the application posture. In this study, we present a novel method for creating digital human models based on seated MR data. An adult-male volunteer was scanned in a simulated driving posture using a FONAR 0.6T upright MRI scanner with a T1 scanning protocol. To compensate for unavoidable image distortion near the edges of the study, images of the same anatomical structures were obtained in transverse and sagittal planes. Combinations of transverse and sagittal images were used to reconstruct the major anatomical features from the buttocks through the knees, including bone, muscle and fat tissue perimeters, using Solidworks® software. For each MR image, B-splines were created as contours for the anatomical structures of interest, and LOFT commands were used to interpolate between the generated Bsplines. The reconstruction of the pelvis, from MR data, was enhanced by the use of a template model generated in previous work CT images. A non-rigid registration algorithm was used to fit the pelvis template into the MR data. Additionally, MR image processing was conducted to both the left and the right sides of the model due to the intended asymmetric posture of the volunteer during the MR measurements. The presented subject-specific, three-dimensional model of the buttocks and thighs will add value to optimisation cycles in automotive seat development when used in simulating human interaction with automotive seats.

Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones : a possible pathological role in subchondral bone sclerosis

Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeo-stasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, im-munohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the os-teocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogene-sis.

Design of LiteSteel Beam floor joists with web opening using an equivalent web thickness method

The LiteSteel Beam (LSB) is an innovative cold-formed steel hollow flange section. When used as floor joists, the LSB sections require holes in the web to provide access for various services. In this study a detailed investigation was undertaken into the elastic lateral distortional buckling behaviour of LSBs with circular web openings subjected to a uniform moment using finite element analysis. Validated ideal finite element models were used first to study the effect of web holes on their elastic lateral distortional buckling behaviour. An equivalent web thickness method was then proposed using four different equations for the elastic buckling analyses of LSBs with web holes. It was found that two of them could be successfully used with approximate numerical models based on solid web elements with an equivalent reduced thickness to predict the elastic lateral distortional buckling moments.

3D reconstruction of long bones utilising magnetic resonance imaging (MRI)

The design of pre-contoured fracture fixation implants (plates and nails) that correctly fit the anatomy of a patient utilises 3D models of long bones with accurate geometric representation. 3D data is usually available from computed tomography (CT) scans of human cadavers that generally represent the above 60 year old age group. Thus, despite the fact that half of the seriously injured population comes from the 30 year age group and below, virtually no data exists from these younger age groups to inform the design of implants that optimally fit patients from these groups. Hence, relevant bone data from these age groups is required. The current gold standard for acquiring such data–CT–involves ionising radiation and cannot be used to scan healthy human volunteers. Magnetic resonance imaging (MRI) has been shown to be a potential alternative in the previous studies conducted using small bones (tarsal bones) and parts of the long bones. However, in order to use MRI effectively for 3D reconstruction of human long bones, further validations using long bones and appropriate reference standards are required. Accurate reconstruction of 3D models from CT or MRI data sets requires an accurate image segmentation method. Currently available sophisticated segmentation methods involve complex programming and mathematics that researchers are not trained to perform. Therefore, an accurate but relatively simple segmentation method is required for segmentation of CT and MRI data. Furthermore, some of the limitations of 1.5T MRI such as very long scanning times and poor contrast in articular regions can potentially be reduced by using higher field 3T MRI imaging. However, a quantification of the signal to noise ratio (SNR) gain at the bone - soft tissue interface should be performed; this is not reported in the literature. As MRI scanning of long bones has very long scanning times, the acquired images are more prone to motion artefacts due to random movements of the subject‟s limbs. One of the artefacts observed is the step artefact that is believed to occur from the random movements of the volunteer during a scan. This needs to be corrected before the models can be used for implant design. As the first aim, this study investigated two segmentation methods: intensity thresholding and Canny edge detection as accurate but simple segmentation methods for segmentation of MRI and CT data. The second aim was to investigate the usability of MRI as a radiation free imaging alternative to CT for reconstruction of 3D models of long bones. The third aim was to use 3T MRI to improve the poor contrast in articular regions and long scanning times of current MRI. The fourth and final aim was to minimise the step artefact using 3D modelling techniques. The segmentation methods were investigated using CT scans of five ovine femora. The single level thresholding was performed using a visually selected threshold level to segment the complete femur. For multilevel thresholding, multiple threshold levels calculated from the threshold selection method were used for the proximal, diaphyseal and distal regions of the femur. Canny edge detection was used by delineating the outer and inner contour of 2D images and then combining them to generate the 3D model. Models generated from these methods were compared to the reference standard generated using the mechanical contact scans of the denuded bone. The second aim was achieved using CT and MRI scans of five ovine femora and segmenting them using the multilevel threshold method. A surface geometric comparison was conducted between CT based, MRI based and reference models. To quantitatively compare the 1.5T images to the 3T MRI images, the right lower limbs of five healthy volunteers were scanned using scanners from the same manufacturer. The images obtained using the identical protocols were compared by means of SNR and contrast to noise ratio (CNR) of muscle, bone marrow and bone. In order to correct the step artefact in the final 3D models, the step was simulated in five ovine femora scanned with a 3T MRI scanner. The step was corrected using the iterative closest point (ICP) algorithm based aligning method. The present study demonstrated that the multi-threshold approach in combination with the threshold selection method can generate 3D models from long bones with an average deviation of 0.18 mm. The same was 0.24 mm of the single threshold method. There was a significant statistical difference between the accuracy of models generated by the two methods. In comparison, the Canny edge detection method generated average deviation of 0.20 mm. MRI based models exhibited 0.23 mm average deviation in comparison to the 0.18 mm average deviation of CT based models. The differences were not statistically significant. 3T MRI improved the contrast in the bone–muscle interfaces of most anatomical regions of femora and tibiae, potentially improving the inaccuracies conferred by poor contrast of the articular regions. Using the robust ICP algorithm to align the 3D surfaces, the step artefact that occurred by the volunteer moving the leg was corrected, generating errors of 0.32 ± 0.02 mm when compared with the reference standard. The study concludes that magnetic resonance imaging, together with simple multilevel thresholding segmentation, is able to produce 3D models of long bones with accurate geometric representations. The method is, therefore, a potential alternative to the current gold standard CT imaging.

Computer planning of stereotactic iodine-125 seed brachytherapy for recurrent malignant gliomas

At St Thomas' Hospital, we have developed a computer program on a Titan graphics supercomputer to plan the stereotactic implantation of iodine-125 seeds for the palliative treatment of recurrent malignant gliomas. Use of the Gill-Thomas-Cosman relocatable frame allows planning and surgery to be carried out at different hospitals on different days. Stereotactic computed tomography (CT) and positron emission tomography (PET) scans are performed and the images transferred to the planning computer. The head, tumour and frame fiducials are outlined on the relevant images, and a three-dimensional model generated. Structures which could interfere with the surgery or radiotherapy, such as major vessels, shunt tubing etc., can also be outlined and included in the display. Catheter target and entry points are set using a three-dimensional cursor controlled by a set of dials attached to the computer. The program calculates and displays the radiation dose distribution within the target volume for various catheter and seed arrangements. The CT co-ordinates of the fiducial rods are used to convert catheter co-ordinates from CT space to frame space and to calculate the catheter insertion angles and depths. The surgically implanted catheters are after-loaded the next day and the seeds left in place for between 4 and 6 days, giving a nominal dose of 50 Gy to the edge of the target volume. 25 patients have been treated so far.