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.

A new model to analyze metaphyseal bone healing in mice

Background: Despite the increasing clinical problems with metaphyseal fractures, most experimental studies investigate the healing of diaphyseal fractures. Although the mouse would be the preferable species to study the molecular and genetic aspects of metaphyseal fracture healing, a murine model does not exist yet. Using a special locking plate system, we herein introduce a new model, which allows the analysis of metaphyseal bone healing in mice. Methods: In 24 CD-1 mice the distal metaphysis of the femur was osteotomized. After stabilization with the locking plate, bone repair was analyzed radiologically, biomechanically, and histologically after 2 (n = 12) and 5 wk (n = 12). Additionally, the stiffness of the bone-implant construct was tested biomechanically ex vivo. Results: The torsional stiffness of the bone-implant construct was low compared with nonfractured control femora (0.23 ± 0.1 Nmm/°versus 1.78 ± 0.15 Nmm/°, P < 0.05). The cause of failure was a pullout of the distal screw. At 2 wk after stabilization, radiological analysis showed that most bones were partly bridged. At 5 wk, all bones showed radiological union. Accordingly, biomechanical analyses revealed a significantly higher torsional stiffness after 5 wk compared with that after 2 wk. Successful healing was indicated by a torsional stiffness of 90% of the contralateral control femora. Histological analyses showed new woven bone bridging the osteotomy without external callus formation and in absence of any cartilaginous tissue, indicating intramembranous healing. Conclusion: With the model introduced herein we report, for the first time, successful metaphyseal bone repair in mice. The model may be used to obtain deeper insights into the molecular mechanisms of metaphyseal fracture healing. © 2012 Elsevier Inc. All rights reserved.

Mechanical considerations in fracture fixation

Bone’s capacity to repair following trauma is both unique and astounding. However, fractures sometimes fail to heal. Hence, the goal of fracture treatment is the restoration of bone’s structure, composition and function. Fracture fixation devices should provide a favourable mechanical and biological environment for healing to occur. The use of internal fixation is increasing as these devices may be applied with less invasive techniques. Recent studies suggest however that, internal fixation devices may be overly stiff and suppresses callus formation. The degree of mechanical stability influences the healing outcome. This is determined by the stiffness of the fixation device and the degree of limb loading. This project aims to characterise the fixation stability of an internal plate fixation device and the influence of modifications to its configuration on implant stability. As there are no standardised methods for the determination of fixation stiffness, the first part of this project aims to compares different methodologies and determines the most appropriate method to characterise the stiffness of internal plate fixators. The stiffness of a fixation device also influences the physiological loads experienced by the healing bone. Since bone adapts to this applied load by undergoing changes through a remodelling process, undesirable changes could occur during the period of treatment with an implant. The second part of this project aims to develop a methodology to quantify remodelling changes. This quantification is expected to aid our understanding of the changes in pattern due to implant related remodelling and on the factors driving the remodelling process. Knowledge gained in this project is useful to understand how the configuration of internal fixation devices can promote timely healing and prevent undesirable bone loss.

Influence of plate bending stiffness on mechanical properties of healing fracture, mouse femora

Mechanically well-defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post-osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post-osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.

The effect of intraoperative force on scoliosis correction at the apex : a biomechanical investigation

Adolescent idiopathic scoliosis (AIS) is a complex 3D deformity of the spine, which may require surgical correction in severe cases. Computer models of the spine provide a potentially powerful tool to virtually ‘test’ various surgical scenarios prior to surgery. Using patient-specific computer models of seven AIS patients who had undergone a single rod anterior procedure, we have recently found that the majority of the deformity correction occurs at the apical joint or the joint immediately cephalic to the apex. In the current paper, we investigate the biomechanics of the apical joint for these patients using clinically measured intra-operative compressive forces applied during implant placement. The aim of this study is to determine a relationship between the compressive joint force applied intra-operatively and the achievable deformity correction at the apical joint.

A computer model to simulate scoliosis surgery

Use of patient-specific computer models as a pre-operative planning tool permits predictions of the likely deformity correction and allows a more detailed investigation of the biomechanical influence of different surgical procedures on the scoliotic spinal anatomy. In this paper, patient-specific computer models are used of adolescent idiopathic scoliosis patients who underwent a single rod anterior procedure at the Mater Children’s Hospital in Brisbane, to predict deformity correction and to investigate the change in biomechanics of the scoliotic spine due to surgical compressive forces applied during implant placement.

Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations : pilot study

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.

Changing patterns of contraceptive use in Australian women

Background: This longitudinal analysis examines how patterns of contraceptive use changed over 11 years among Australian women born between 1973 and 1978. Study Design: The analysis included 6708 women sampled from the Australian universal health insurance database who completed four self-report postal surveys between 1996 and 2006. Change over time in use of any method of contraception and the common single methods of the oral contraceptive pill and condom was examined using a longitudinal logistic regression model. Results: The oral contraceptive pill was the most commonly used single method at each survey (27-44%) but decreased over time. Over time, contraceptive users were increasingly more likely to be single or in a de facto relationship or to have had two or more births. Conclusions: Women's contraceptive use and the factors associated with contraceptive use change over time as women move into relationships, try to conceive, have babies and complete their families.

Correction of step artefact associated with MRI scanning of long bones

3D models of long bones are being utilised for a number of fields including orthopaedic implant design. Accurate reconstruction of 3D models is of utmost importance to design accurate implants to allow achieving a good alignment between two bone fragments. Thus for this purpose, CT scanners are employed to acquire accurate bone data exposing an individual to a high amount of ionising radiation. Magnetic resonance imaging (MRI) has been shown to be a potential alternative to computed tomography (CT) for scanning of volunteers for 3D reconstruction of long bones, essentially avoiding the high radiation dose from CT. In MRI imaging of long bones, the artefacts due to random movements of the skeletal system create challenges for researchers as they generate inaccuracies in the 3D models generated by using data sets containing such artefacts. One of the defects that have been observed during an initial study is the lateral shift artefact occurring in the reconstructed 3D models. This artefact is believed to result from volunteers moving the leg during two successive scanning stages (the lower limb has to be scanned in at least five stages due to the limited scanning length of the scanner). As this artefact creates inaccuracies in the implants designed using these models, it needs to be corrected before the application of 3D models to implant design. Therefore, this study aimed to correct the lateral shift artefact using 3D modelling techniques. The femora of five ovine hind limbs were scanned with a 3T MRI scanner using a 3D vibe based protocol. The scanning was conducted in two halves, while maintaining a good overlap between them. A lateral shift was generated by moving the limb several millimetres between two scanning stages. The 3D models were reconstructed using a multi threshold segmentation method. The correction of the artefact was achieved by aligning the two halves using the robust iterative closest point (ICP) algorithm, with the help of the overlapping region between the two. The models with the corrected artefact were compared with the reference model generated by CT scanning of the same sample. The results indicate that the correction of the artefact was achieved with an average deviation of 0.32 ± 0.02 mm between the corrected model and the reference model. In comparison, the model obtained from a single MRI scan generated an average error of 0.25 ± 0.02 mm when compared with the reference model. An average deviation of 0.34 ± 0.04 mm was seen when the models generated after the table was moved were compared to the reference models; thus, the movement of the table is also a contributing factor to the motion artefacts.

Ability of modal analysis to detect osseointegration of implants in transfemoral amputees : a physical model study

Owing to the successful use of non-invasive vibration analysis to monitor the progression of dental implant healing and stabilization, it is now being considered as a method to monitor femoral implants in transfemoral amputees. This study uses composite femur-implant physical models to investigate the ability of modal analysis to detect changes at the interface between the implant and bone simulating those that occur during osseointegration. Using electromagnetic shaker excitation, differences were detected in the resonant frequencies and mode shapes of the model when the implant fit in the bone was altered to simulate the two interface cases considered: firm and loose fixation. The study showed that it is beneficial to examine higher resonant frequencies and their mode shapes (rather than the fundamental frequency only) when assessing fixation. The influence of the model boundary conditions on the modal parameters was also demonstrated. Further work is required to more accurately model the mechanical changes occurring at the bone-implant interface in vivo, as well as further refinement of the model boundary conditions to appropriately represent the in vivo conditions. Nevertheless, the ability to detect changes in the model dynamic properties demonstrates the potential of modal analysis in this application and warrants further investigation.

More is not necessarily better. A biomechanical study on distal screw numbers in volar locking distal radius plates

INTRODUCTION: Currently available volar locking plates for the treatment of distal radius fractures incorporate at least two distal screw rows for fixation of the metaphyseal fragment and have a variable-angle locking mechanism which allows placement of the screws in various directions There is, however no evidence that these plates translate into better outcomes or have superior biomechanical properties to first generation plates, which had a single distal screw row and fixed-angle locking. The aim of our biomechanical study was to compare fixed-angle single-row plates with variable-angle multi-row plates to clarify the optimal number of locking screws. MATERIALS AND METHODS: Five different plate-screw combinations of three different manufacturers were tested, each group consisting of five synthetic fourth generation distal radius bones. An AO type C2 fracture was created and the fractures were plated according to each manufacturer's recommendations. The specimens then underwent cyclic and load-to-failure testing. An optical motion analysis system was used to detect displacement of fragments. RESULTS: No significant differences were detected after cyclic loading as well as after load-to-failure testing, neither in regard to axial deformation, implant rigidity or maximum displacement. The fixed-angle single-row plate showed the highest pre-test rigidity, least increase in post-testing rigidity and highest load-to-failure rigidity and least radial shortening. The radial shortening of plates with two distal screw rows was 3.1 and 4.3 times higher, respectively, than that of the fixed-angle single-row plate. CONCLUSION: The results of our study indicate that two distal screw rows do not add to construct rigidity and resistance against loss of reduction. Well conducted clinical studies based on the findings of biomechanical studies are necessary to determine the optimal number of screws necessary to achieve reproducibly good results in the treatment of distal radius fractures.

Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles

Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic approaches. As there is also an increasing body of evidence suggesting that successful lasting tissue reconstruction requires an implant that mimics natural tissue organization, it is imperative that depth-dependent characteristics of equine osteochondral tissue are known, to assess to what extent they resemble those in humans. Therefore, osteochondral cores (4-8 mm) were obtained from the medial and lateral femoral condyles of equine and human donors. Cores were processed for histology and for biochemical quantification of DNA, glycosaminoglycan (GAG) and collagen content. Equine and human osteochondral tissues possess similar geometrical (thickness) and organizational (GAG, collagen and DNA distribution with depth) features. These comparable trends further underscore the validity of the equine model for the evaluation of regenerative approaches for articular cartilage.

Reproductive health : findings from the Australian Longitudinal Study on Women’s Health. Chapter 3: Use of contraception

Chapter 3: Use of contraception. p15-32 Key findings: This section examines trends in the use of contraception between 1996 and 2006 by women who participated in the surveys for the 1973-1978 cohort of the Australian Longitudinal Study on Women’s Health. 1. The oral contraceptive pill was the most commonly used method of contraception at each survey, but its use decreased over time. 2.Of women who consistently used contraception, 40% used the oral contraceptive pill as their only method of contraception in at least three out of four surveys. 3. The proportion of women using condoms as their only method of contraception remained steady over time (15-18%) but only 3% of all women used condoms only at every survey. 4. The proportion of women using both condoms and the oral contraceptive pill remained steady at 13-14% of all women from Survey 1 to 3, but decreased to 8% of all women at Survey 4. 5. The use of methods other than the oral contraceptive pill and/or condoms increased at Survey 4. 6. The proportion of women using an implant (e.g. Implanon) remained steady between Surveys 3 and 4, with 3% of women using an implant only. Around one third of implant users at Survey 3 continued to use this method at Survey 4. 7. The main reasons for not using contraception at Surveys 3 and 4 were pregnancy, trying to conceive, or no male sexual partners. 8. Women who used contraception were more likely to be in de facto relationships or single, be up to date with Pap tests and have had two or more births. 9. Women who did not use contraception were more likely to be non-drinkers and/or do low levels of exercise, have had one birth and have experienced miscarriage. 10. Contraception changed in expected ways according to reproductive events: women who reported only miscarriages between surveys also stopped using contraception in the same period; most women who did not report reproductive events continued to use the same method of contraception; and women who had a termination tended to switch methods.

Area of residence is associated with Australian women’s uptake of long-acting contraception

Objective: Several new types of contraception became available in Australia over the last twelve years (the implant in 2001, progestogen intra-uterine device (IUD) in 2003, and vaginal contraceptive ring in 2007). Most methods of contraception require access to health services. Permanent sterilisation and the insertion of an implant or IUD involve a surgical procedure. Access to health professionals providing these specialised services may be more difficult in rural areas. This paper examines uptake of permanent or long-acting reversible contraception (LARCs) among Australian women in rural areas compared to women in urban areas. Method: Participants in the Australian Longitudinal Study on Women's Health born in 1973-78 reported on their contraceptive use at three surveys: 2003, 2006 and 2009. Contraceptive methods included permanent sterilisation (tubal ligation, vasectomy), non-daily or LARC methods (implant, IUD, injection, vaginal ring), and other methods including daily, barrier or "natural" methods (oral contraceptive pills, condoms, withdrawal, safe period). Sociodemographic, reproductive history and health service use factors associated with using permanent, LARC or other methods were examined using a multivariable logistic regression analysis. Results: Of 9,081 women aged 25-30 in 2003, 3% used permanent methods and 4% used LARCs. Six years later in 2009, of 8,200 women (aged 31-36), 11% used permanent methods and 9% used LARCs. The fully adjusted parsimonious regression model showed that the likelihood of a woman using LARCs and permanent methods increased with number of children. Women whose youngest child was school-age were more likely to use LARCs (OR=1.83, 95%CI 1.43-2.33) or permanent methods (OR=4.39, 95%CI 3.54-5.46) compared to women with pre-school children. Compared to women living in major cities, women in inner regional areas were more likely to use LARCs (OR=1.26, 95%CI 1.03-1.55) or permanent methods (OR=1.43, 95%CI 1.17-1.76). Women living in outer regional and remote areas were more likely than women living in cities to use LARCs (OR=1.65, 95%CI 1.31-2.08) or permanent methods (OR=1.69, 95%CI 1.43-2.14). Women with poorer access to GPs were more likely to use permanent methods (OR=1.27, 95%CI 1.07-1.52). Conclusions: Location of residence and access to health services are important factors in women's choices about long-acting contraception in addition to the number and age of their children. There is a low level of uptake of non-daily, long-acting methods of contraception among Australian women in their mid-thirties.

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction. We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini- open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. Methods. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion was assessed at six months post-surgery. Results. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL- based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL- based scaffold group in all loading directions in comparison to the other two groups. Conclusions. The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.