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Bone & Joint Open
Vol. 2, Issue 11 | Pages 1004 - 1016
26 Nov 2021
Wight CM Whyne CM Bogoch ER Zdero R Chapman RM van Citters DW Walsh WR Schemitsch E

Aims

This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads.

Methods

In all, six 28 mm and six 36 mm titanium stem-cobalt chrome head pairs with polyethylene sockets were tested in a novel instrumented hip simulator. Samples were tested using simulated gait data with incremental increasing loads to determine corrosion onset load and electrochemical activity. Half of each head size group were then cycled with simulated gait and the other half with gait compression only. Damage was measured by area and maximum linear wear depth.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 35 - 35
1 Sep 2012
Lo V Akens M Wise-Milestone L Yee A Wilson B Whyne CM
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Purpose

Maintenance of vertebral mechanical stability is of paramount importance to prevent pathologic fractures and resultant neurologic compromise in individuals with spinal metastases. Current non-surgical treatments for vertebral metastases (i.e. chemotherapy, bisphophonates (BP) and radiation) yield variable responses in the tumour and surrounding bone. Photodynamic therapy (PDT) is a novel, minimally-invasive technology that utilizes a drug activated by light at a specific non-thermal wavelength to locally destroy tumour cells. Previously, we observed that PDT can ablate cancer cells within bone and yield short-term (1-week) improvements in vertebral architecture and biomechanical strength, particularly when combined with BP therapy. This study aims to evaluate the effects of PDT in vertebral bone over a longer (6-week) time period, alone and combined with previous BP treatment, to determine if improvements in skeletal architecture and strength are maintained.

Method

Fourty healthy rnu/rnu rats were randomly assigned to four treatment groups: (i) untreated control, (ii) BP only, (iii) PDT only and (iv) PDT following BP. BP treatments were administered on day 0 via subcutaneous injection of zoledronic acid. PDT was administered on day 7 via an intravenous injection of BPD-MA photosensitizer. A flat-cut optical fiber was inserted percutaneously adjacent to lumbar vertebra L2. After a 15-minute drug-light interval, 75J of light energy was delivered from a 690nm laser. Six weeks later, animals were euthanized. Structural properties of excised L2 vertebral bodies were quantified through semi-automated analysis of micro-CT images. In of the specimens, mechanical properties were evaluated by loading the L2 vertebral body to failure in axial compression. The remaining L2 vertebrae were analyzed for morphology, osteoid formation and osteoclast activity using histological methods.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 32 - 32
1 Sep 2012
Whyne CM Leckie A Akens M Woodhouse K Yee A
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Purpose

Nucleus pulposus (NP) replacements represent a less invasive alternative for treatment of early stage degenerative disc disease (DDD). Hydrogel based NP replacements are of particular interest as they can be injected/implanted using minimally invasive surgical (MIS) techniques to re-establish mechanical integrity and as a scaffold for regeneration. A thiol-modified hyaluronan elastin-like polypeptide (TMHA/EP) hydrogel crosslinked using polyethylene diacrylate has shown promise as a potential NP replacement for DDD in vitro. This study aims to assess the mechanical properties of this hydrogel when injected into an induced early stage DDD porcine model and to determine the optimal injection method for delivery. It is hypothesized that minimally invasive injection of the TMHA/EP material can restore mechanical behaviour of spinal motion segments in early stage DDD.

Method

Intervertebral disc (IVD) degeneration was enzymatically induced in L2-L3 and L4-L5 lumbar levels in 10 Yorkshire boars using chondroitinase ABC (n=20 discs). An additional three animals served as healthy controls (n=6 discs). Following a four-week degradation period, the TMHA/EP solution (250microL in a 3:1 weight ratio) was injected into the degenerate NP of 16 discs by one of two MIS techniques: A direct 18G needle injection or a modified kyphoplasty technique (MKT) in which a balloon angiocatheter was inserted through an 11G trocar into the IVD and inflated to create a cavitary defect that was then filled with the hydrogel. Excised motion segments were tested in axial compression under a load of 400N and in axial rotation (AR), lateral bending (LB) and flexion/extension (FE) at 5Nm. Range of motion (ROM), neutral zone (NZ) length, NZ stiffness (NZStiff) and axial compressive stiffness (ACStiff) were quantified.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 39 - 39
1 Sep 2012
Hojjat S Wise-Milestone L Whyne CM
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Purpose

To develop a low complexity highly-automated multimodal approach to segment vertebral structure and quantify mixed osteolytic/osteoblastic metastases in the rat spine using a combination of CT and MR imaging. We hypothesize that semi-automated multimodal analysis applied to 3D CT and MRI reconstructions will yield accurate and repeatable quantification of whole vertebrae affected by mixed metastases.

Method

Mixed spinal metastases were developed via intra-cardiac injection of canine Ace-1 luciferase transfected prostate cancer cells in a 3 week old rnu/rnu rat. Two sequential MR images of the L1-L3 vertebral motion segments were acquired using a 1H quadrature customized birdcage coil at 60 m isotropic voxel size followed by CT imaging at a 14m isotropic voxel size. The first MR image was T1 weighted to highlight the trabecular structure to ensure accurate registration with the CT image. The second MR image was T2 weighted to optimize differentiation between bone marrow and osteolytic tumour tissue. Samples were then processed for undecalcified histology and stained with Goldners Trichrome to identify mineralized bone and unmineralized new bone formation.

All images were resampled to 34.9 m and manually aligned to a global axis. This was followed by an affine registration using a Quasi Newton optimizer and a Normalized Mutual Information metric to ensure accurate registration. The whole individual vertebrae and their trabecular centrums were then segmented from the CT images using an extended version of a previously developed atlas based registration algorithm. An intensity-based thresholding method was used to segment the regions corresponding to osteoblastic tumor predominantly attached to the outside of the cortical shell. The whole vertebral segmentation from the CT was warped around the T2 weighted MR to define the bone boundaries. An intensity-based thresholding approach was then applied to the T2 weighted MR segment the osteolytic tumor.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 200 - 200
1 Sep 2012
Crookshank MC Edwards M Sellan M Whyne CM Schemitsch EH
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Purpose

Femoral shaft fractures are routinely treated using antegrade intramedullary nailing under fluoroscopic guidance. Malreduction is common and can be due to multiple factors. Correct entry point identification can help minimize malreduction and the risk of iatrogenic fracture. This study aims to compare landmark identification used to guide nail entry, the piriformis fossa (PF) and the trochanteric tip (T), via computer navigation and conventional fluoroscopy.

Method

The location of the PF and T were digitized under direct visualization with a three-dimensional scribe on ten, fresh-frozen cadaveric right femora (two male, eight female) by three fellowship trained orthopaedic surgeons. To estimate inter- and intraobserver reliability of the direct measurements, an intraclass correlation coefficient was calculated with a minimum of two weeks between measurements. Under navigation, each specimen was draped and antero-posterior (AP) and lateral radiographs of the proximal femur were taken with a c-arm and image intensifier. The c-arm was positioned in a neutral position (0 for AP, 90 for lateral) and rotated in 5 increments, yielding a range of acceptable images. Images, in increments of 5, within the AP range (with a neutral lateral) were loaded into a navigation system (Stryker, MI). A single surgeon digitized the T and PF directly based on conventional fluoroscopy, and again directed by navigation, yielding two measurements per entry point per specimen. This was repeated for the lateral range. Hierarchical linear modelling and a Wilcox rank test were used to determine differences in accuracy and precision, respectively, in the identification of PF and T using computer navigation vs. conventional fluoroscopy.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 69 - 69
1 Sep 2012
Wright DA Meguid M Lubovsky O Whyne CM
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Purpose

Based on a structure function relationship, bone density distribution has been described as being representative of skeletal loading. As such, computed tomography (CT) may be used to visualize the structure of femoral head subchondral bone to allow in vivo quantification of joint mechanics without the need for implanted hardware. This study aims to characterize the distribution of subchondral bone density in the femoral head. We hypothesize that a non-uniform distribution of bone density will be observed, with correlation between left and right sides for a given patient.

Method

Femoral head surfaces were created bilaterally for thirty patients through semi-automatic segmentation of reconstructed CT data and used to map bone density, by shrinking them into the subchondral bone and averaging the grey values (linearly related to bone density) within five millimeters of the articular surface. Density maps were then oriented with the center of the head at the origin, the femoral mechanical axis (FMA) aligned with the vertical, and the posterior condylar axis (PCA) aligned with the horizontal. Twelve regions were created by dividing the density maps into three concentric rings at increments of thirty degrees from the horizontal, then splitting into four quadrants along the anterior-posterior and medial-lateral axes. Average bone density within each region was then calculated using histogram analysis. All analysis was performed with AmriaDEV 5.2.2 image analysis software (Visage Imaging, Carlsbad USA).


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 562 - 562
1 Nov 2011
Hojjat S Whyne CM
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Purpose: To examine the effect of image resolution and structural model on quantifying architectural differences between healthy and metastatically involved vertebrae.

Method: Lumbar vertebrae of healthy(n=6) and meta-statically involved(n=6) rnu/rnu rats were utilized. Osteolytic vertebral metastases were developed via intracardiac injection of human MT1 breast cancer cells. μCT images of the vertebrae were acquired ex vivo at 14μ isotropic spatial resolution. The whole vertebrae were segmented using an automated atlas based demons deformable registration followed by level set curvature evolutions. A subsequent iteration of level set was used to yield a segmentation of the trabecular centrum. The individual trabecular network was further segmented using intensity based thresholding. Architectural parameters were computed from the segmented μCT images: Cortical Bone Volume(CBV), Trabecular Bone Volume(TBV), Trabecular Bone Surface Area and the degree of anisotropy based on Mean Intercept Length(MIL). From this, trabecular Thickness(TbTh), Trabecular Number(TbN) and Trabecular Separation(TbS) were calculated using the Parfitt Model (Parfitt, Bone & Mineral. 1987). TbTh was also calculated separately using the Hilderbrand model (Hilderbrand, J of Microscopy 1997). The degree of anisotropy was determined via Mean Intercept Length (MIL) measured utilizing a binary shift/subtraction approach. The measures of TbTh and MIL were compared for each image at 8.725(high), 17.45(medium) and 34.9(low) μm3 isotropic spatial resolutions.

Results: Parfitt’s plate model showed a significant decrease in TBV, TbN and CBV and a significant increase in TbS in the metastatic vertebrae in comparison to the healthy group at the highest resolution. In both Hilderbrand’s and Parfitt’s models at the highest resolution there was no significant difference in TbTh between the healthy and metastatic groups. In both models, TbTh and TbS values rose while TBV and TbN decreased as the resolution was lowered. Significant reductions were observed only in TbTh between the healthy and metastatic vertebrae at the medium and low resolutions. In all cases, the Hildebrand model yielded lower values of TbTh than the Parfitt model. However, achieving robust automated results using the Hildebrand method was limited in the final stage of the segmentation due to sensitivity to small islands of bone. Structural anisotropy remained consistent in all groups at all resolutions, with ~3x greater MIL in the superior/inferior direction. The degree of anisotropy was, however, consistent in both groups suggesting that the metastatic destruction does not have any directional preference.

Conclusion: The automated use of Parfitt’s plate model along with the MIL method can be used to yield quantitative analyses demonstrating differences in vertebral microstructure due to metastatic involvement. However the sensitivity of these architectural parameters to resolution motivates the need for high resolution scanning in future preclinical applications.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 551 - 551
1 Nov 2011
Li R Atesok K Wright D Nauth A Whyne CM Schemitsch EH
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Purpose: Severe fractures damage blood vessels and disrupt circulation at the fracture site resulting in an increased risk of poor fracture healing. Endothelial progenitor cells (EPCs) are bone-marrow derived cells with the ability to differentiate into endothelial cells and contribute to neovascularization and re-endothelialization after tissue injury and ischemia. We have previously reported that EPC therapy resulted in improved radiographic healing and histological blood vessel formation in a rat fracture model. The purpose of this study was to further quantify the effects of EPC therapy with microCT and biomechanical analyses.

Method: Five-millimeter segmental defects were created and stabilized in the femora of 14 fisher 344 rats. The treatment group (n=7) received 1x106 EPCs within gelfoam locally at the area of the bone defect and control animals (n=7) received only saline-gelfoam with no cells. The formation and healing of bone after 10 weeks were asessed by radiographic, micro-CT and biomechanical analyses.

Results: Radiographically all the animals in EPC-treated group healed with bridging callus formation, whereas control group animals demonstrated radiographic non-union. Micro-CT assessment demonstrated significantly improved parameters of bone volume (35.34 to 20.68 mm3, p=0.000), bone volume density (0.24 to 0.13%, p=0.001), connectivity density (25.13 to 6.15%, p=0.030), trabecular number (1.14 to 0.51 1/mm, p=0.000), trabecular thickness (0.21 to 0.26 mm, p=0.011), trabecular spacing (0.71 to 1.88 mm, p=0.002), bone surface area (335.85 to 159.43mm, p=0.000), and bone surface to bone volume ratio (9.43 to 7.82 1/mm, p=0.013) in the defect site for the EPC group versus the control group respectively. Biomechanical testing showed that the EPC treatment group had a significantly higher torsional strength compared with the control group (EPC=164.6±27.9 Nmm, Control=29.5±3.8 Nmm; p value = 0.000). Similarly, the EPC treated fractures demonstrated significantly higher torsional stiffness versus controls (EPC=30.3±5.0 Nmm/ deg, Control=0.9±0.1 Nmm/deg; p value = 0.000). When biomechanically compared to contralateral intact limbs, the EPC treated limbs had similar torsional stiffness (p=0.996), but significantly lower torsional strength (p=0.000) and smaller angle of twist (p=0.002).

Conclusion: These results suggest that local EPC therapy significantly enhances fracture healing in an animal model. The biomechanical results show that control animals develop a mechanically unstable non-union. In contrast, EPC therapy results in fracture healing that restores the biomechanical properties of the fractured bone closer to that of intact bone.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 563 - 563
1 Nov 2011
Akens MK Won E Wise-Milestone L Wilson BC Yee AJ Whyne CM
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Purpose: Bony metastases in vertebrae secondary to breast cancer can result in osteolysis and an increase in skeletal related events. Bisphosphonates (BP) are the current standard of care for breast cancer patients with skeletal disease. Photodynamic therapy (PDT) is a non-radiative treatment, which has been successfully applied to various malignancies and shown to successfully ablate vertebral human breast cancer (MT1) metastases in a murine model. Previous in-vitro study has shown that pre-treatment of MT-1 cells with the BP zoledronic acid (Zometa®) renders them more susceptible to PDT. The aim of this study was to evaluate the influence of pre-treatment with BPs on the effect of PDT treatment on tumour ablation in metastatically involved vertebrae in vivo.

Method: Metastases were induced in fourteen 5–6 weeks old female athymic rats (Hsd:RH-Foxn1rnu) by intra-cardiac injection of 2x10^6 MT-1 cells. Four groups were formed:

control, no treatment;

BP only;

PDT only;

BP and PDT combined.

Seven days after MT-1 injection 60 μg/kg of zoledronic acid was injected. PDT treatment was administered on day 14 using the photosensitizer BPD-MA (1.0 mg/kg; Visudyne). Fifteen minutes later, laser-light (690nm; 75J) was administered to the lumbar vertebrae. The rats were euthanized 7 days after PDT treatment. A total of 45 vertebrae were evaluated using a histomorphometric program (GENIE™, Aperio) to assess tumour burden. Statistical analyses were performed using a one-way ANOVA with a Tukey post hoc test. A p-value p< .05 was considered to be statistically significant..

Results: The total The total tumour burden within vertebrae of rats pre-treated with BP and/or PDT was significantly lower compared to the control rats (p< .001). In addition, the PDT alone treated group demonstrated significantly less tumour burden than the combined BP+PDT group. In the control and BP-only groups, large tumours were found to include regions of necrosis. The PDT treatment groups (PDT and BP+PDT) exhibited areas of necrosis throughout the entire vertebral bodies with adjacent formation of granulation tissue.

Conclusion: BP, PDT and combined BP+PDT treatments resulted in a lower overall tumour burden at day 21 post MT-1 cell injection compared to control rats. A surprising increased level of tumour burden was found in comparing the combined treatment group to the PDT-only group. These findings are in contrast to previous in-vitro results, where the pre-treatment with BPs made the cells more susceptible to PDT. Pre-treatment with BP affects both the bone and tumour cells, and as such may induce different cellular pathways in response to PDT treatment. However, the ability of PDT applied at day 14 to cause a similar reduction in tumour burden compared to BP treatment at day 7, suggests its ability to rapidly and effectively ablate the tumour within the bone, even in the presence of BP.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 225 - 225
1 May 2009
Hardisty M Akens M Skrinskas T Whyne CM Yee A Toronto O
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Rodents are often used as preclinical models for investigating the biomechanical consequences of spinal pathologies and interventions. Growth plates are present within rat vertebrae throughout life and may alter the vertebral biomechanics. This study investigates the biomechanical response of rat-tail vertebrae to axial compressive loading using μCT imaging and image registration to spatially resolve strain fields.

The sixth caudal vertebrae of eight immunocompromised (rnu/rnu) rats were μCT scanned (17.5 ×17.5×17.5μm/pixel) in both loaded (27N-32N axial compression) and unloaded configurations. Image registration was used to calculate strain and displacement fields in the bone due to the applied load by finding a spatial mapping between the two scans. Strain was resolved to varying spatial resolutions; high strain gradient regions, such as the growth plates, were analyzed to higher spatial resolutions.

Axial strains calculated by image registration ranged from 2% in tension to 16% in compression with an average axial strain of 1.6% in compression. In seven rats the majority of the strain measured within the vertebrae was concentrated in the growth plate. Very soft growth plates in three specimens resulted in maximum axial strains from 10–16% in compression. The remaining four rats with strain concentrations in the growth plate had maximum axial strains ranging from 2.2%–3.2%. Centrally located strain concentrations of lower magnitudes and more limited spatial extent were observed in the trabecular bone.

The majority of the strain within the rat vertebrae was absorbed by the growth plates. The amount of strain within the growth plate is important to consider when interpreting biomechanical data on rat vertebrae. Load application to rodent vertebrae will first compress the growth plate and only following compression of this structure cause significant development of displacement and strains within the trabecular and cortical bone. This insight into the biomechanical response of rat vertebrae is apparent through the application of image registration to analyse vertebral body behaviour; such information would not be evident in analysing preclinical whole vertebral body response using finite element modeling or experimental testing protocols.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 226 - 226
1 May 2009
Hardisty M Sigal I Skrinskas T Whyne CM
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To compare strains measured in a whole rat-tail vertebra by image registration (IM) with those predicted by solid finite element analysis (FEA). Quantification of bone strain allows better understand fracture risk, bone healing and turnover.

The sixth caudal vertebra of an rnu/rnu rat was μCT scanned (17.5×17.5×17.5μm/voxel) while loaded (27N axial compression) and unloaded. IM was used to calculate strain and displacement fields in the bone due to the applied load by finding a spatial mapping between the two scans. Strain was resolved to varying spatial resolution; high strain gradient regions (ie growth plates) were analyzed to higher spatial resolutions. A FE model was created of the unloaded vertebra, consisting of tetrahedral elements with transversely isotropic material properties. Elements were assigned elastic moduli based upon μCT image intensities. Growth plate moduli ranged from 0–150kPa and the bone moduli ranged from 0.2–15000MPa. Vertebral geometry was created through segmentation of μCT images. Displacement boundary conditions were obtained by matching cranial and caudal surfaces in the unloaded and loaded scans. The displacement fields of the two methods were compared by using the fields calculated to deform the unloaded scan to match the loaded scan. The strains were compared by plotting FEA measured axial strain against IM calculated axial strain.

The displacement fields calculated by both methods were able to spatially align the unloaded scan to the loaded scan (Mean Voxel Intensity Difference: FEA=441HU, IM=328HU, Unregistered=969HU). IM and FEA show very limited agreement in axial strain measurement (R2=0.388, Slope=0.75, X-Intercept=0.0037) although both calculated high axial strains in the growth plates and low axial strains in the trabecular and cortical bone. Good agreement was found in the mean axial strain measured by both methods (IM= −0.044, FEA=−0.037). IM was better able to deal with difficulties in quantifying bone strain due to the growth plate than FEA.

IM presents advantages over FEA in measuring strain in complex whole bone trabecular structures, however has lower spatial resolution than is possible with FEA.