Independent measurement of femoral cortical thickness and cortical bone density using clinical CT.

The local structure of the proximal femoral cortex is of interest since both fracture risk, and the effects of various interventions aimed at reducing that risk, are associated with cortical properties focused in particular regions rather than dispersed over the whole bone. Much of the femoral cortex is less than 3mm thick, appearing so blurred in clinical CT that its actual density is not apparent in the data, and neither thresholding nor full-width half-maximum techniques are capable of determining its width. Our previous work on cortical bone mapping showed how to produce more accurate estimates of cortical thickness by assuming a fixed value of the cortical density for each hip. However, although cortical density varies much less over the proximal femur than thickness, what little variation there is leads to errors in thickness measurement. In this paper, we develop the cortical bone mapping technique by exploiting local estimates of imaging blur to correct the global density estimate, thus providing a local density estimate as well as more accurate estimates of thickness. We also consider measurement of cortical mass surface density and the density of trabecular bone immediately adjacent to the cortex. Performance is assessed with ex vivo clinical QCT scans of proximal femurs, with true values derived from high resolution HRpQCT scans of the same bones. We demonstrate superior estimation of thickness than is possible with alternative techniques (accuracy 0.12 ± 0.39 mm for cortices in the range 1-3mm), and that local cortical density estimation is feasible for densities >800 mg/cm(3).This is the accepted manuscript of an article published in Medical Image Analysis (GM Treece, AH Gee, Medical Image Analysis 2015, 20(1), 249–264

How does the femoral cortex depend on bone shape? A methodology for the joint analysis of surface texture and shape.

In humans, there is clear evidence of an association between hip fracture risk and femoral neck bone mineral density, and some evidence of an association between fracture risk and the shape of the proximal femur. Here, we investigate whether the femoral cortex plays a role in these associations: do particular morphologies predispose to weaker cortices? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm2) in a cohort of 125 females. Principal component analysis of the femoral surfaces identified three modes of shape variation accounting for 65% of the population variance. We then used statistical parametric mapping (SPM) to locate regions of the cortex where CMSD depends on shape, allowing for age. Our principal findings were increased CMSD with increased gracility over much of the proximal femur; and decreased CMSD at the superior femoral neck, coupled with increased CMSD at the calcar femorale, with increasing neck-shaft angle. In obtaining these results, we studied the role of spatial normalization in SPM, identifying systematic misregistration as a major impediment to the joint analysis of CMSD and shape. Through a series of experiments on synthetic data, we evaluated a number of registration methods for spatial normalization, concluding that only those predicated on an explicit set of homologous landmarks are suitable for this kind of analysis. The emergent methodology amounts to an extension of Geometric Morphometric Image Analysis to the domain of textured surfaces, alongside a protocol for labelling homologous landmarks in clinical CT scans of the human proximal femur

Calibration of an orientation sensor for freehand 3D ultrasound and its use in a hybrid acquisition system

BACKGROUND: Freehand 3D ultrasound is a powerful imaging modality with many potential applications. However, its reliance on add-on position sensors, which can be expensive, obtrusive and difficult to calibrate, is a major drawback. Alternatively, freehand 3D ultrasound can be acquired without a position sensor using image-based techniques. Sensorless reconstructions exhibit good fine scale detail but are prone to tracking drift, resulting in large scale geometrical distortions. METHOD: We investigate an alternative position sensor, the Xsens MT9-B, which is relatively unobtrusive but measures orientation only. We describe a straightforward approach to calibrating the sensor, and we measure the calibration precision (by repeated calibrations) and the orientation accuracy (using independent orientation measurements). We introduce algorithms that allow the MT9-B potentially to correct both linear and angular drift in sensorless reconstructions. RESULTS: The MT9-B can be calibrated to a precision of around 1 degrees . Reconstruction accuracy is also around 1 degrees . The MT9-B was able to eliminate angular drift in sensorless reconstructions, though it had little impact on linear drift. In comparison, six degree-of-freedom drift correction was shown to produce excellent reconstructions. CONCLUSION: Gold standard freehand 3D ultrasound acquisition requires the synthesis of image-based techniques, for good fine scale detail, and position sensors, for good large scale geometrical accuracy. A hybrid system incorporating the MT9-B offers an attractive compromise between quality and ease of use. The position sensor is unobtrusive and the system is capable of faithful acquisition, with the one exception of linear drift in the elevational direction

A new quantitative 3D approach to imaging of structural joint disease.

Imaging of joints with 2D radiography has not been able to detect therapeutic success in research trials while 3D imaging, used regularly in the clinic, has not been approved for this purpose. We present a new 3D approach to this challenge called joint space mapping (JSM) that measures joint space width in 3D from standard clinical computed tomography (CT) data, demonstrating its analysis steps, technical validation, and reproducibility. Using high resolution peripheral quantitative CT as gold standard, we show a marginal over-estimation in accuracy of +0.13 mm and precision of ±0.32 mm. Inter-operator reproducibility bias was near-zero at -0.03 mm with limits of agreement ±0.29 mm and a root mean square coefficient of variation 7.5%. In a technical advance, we present results from across the hip joint in 3D with optimum validation and reproducibility metrics shown at inner joint regions. We also show JSM versatility using different imaging data sets and discuss potential applications. This 3D mapping approach provides information with greater sensitivity than reported for current radiographic methods that could result in improved patient stratification and treatment monitoring

Association between femur size and a focal defect of the superior femoral neck.

Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a role in this association: might larger femurs harbour focal, cortical defects? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm(2)) in cohorts of 308 males and 125 females. Principal component analysis of the various femoral surfaces led to a measure of size that is linearly independent from shape. After mapping the data onto a canonical femur surface, we used statistical parametric mapping to identify any regions where CMSD depends on size, allowing for other confounding covariates including shape. Our principal finding was a focal patch on the superior femoral neck, where CMSD is reduced by around 1% for each 1% increase in proximal-distal size (p<0.000005 in the males, p<0.001 in the females). This finding appears to be consistent with models of functional adaptation, and may help with the design of interventional strategies for reducing fracture risk.KESP acknowledges the support of the NIHR Biomedical Research Centre, Cambridge, and funding from Arthritis Research UK (reference 20109). The MrOS study is supported by National Institutes of Health (NIH) funding. The following institutes provide support: the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences and the NIH Roadmap for Medical Research, under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160 and UL1 TR000128.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.bone.2015.06.024

Predicting Hip Fracture Type With Cortical Bone Mapping (CBM) in the Osteoporotic Fractures in Men (MrOS) Study.

Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual-energy X-ray (DXA)-based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have subdivided fracture into types, because this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The Osteoporotic Fractures in Men (MrOS) study is a predictive case-cohort study of men over 65 years old: we analyze 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5994. To our knowledge, this is the largest QCT-based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We show that both cortical mass surface density and endocortical trabecular BMD are significantly different in fracture cases versus cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA-based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave-one-out cross-validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 for trochanteric fractures and 0.76 to 0.82 for femoral neck fractures. In contrast, adding DXA-based BMD to a CBM-based predictive model does not result in any significant improvement.The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Ageing (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. GMT, AHG, DMB and KESP contributed to the conception and design of the study. All authors were involved in the analysis or interpretation of the data, contributed to the manuscript, and approved the final version. KESP acknowledges the support of the NIHR Biomedical Research Centre, Cambridge. KESP received funding from Arthritis Research UK (ARUK ref. no. 20109). GMT takes responsibility for the integrity of the data analysis.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.255

An exploratory study into measuring the cortical bone thickness from CT in the presence of metal implants

Purpose The aim of this study was to develop and evaluate a method for measuring the cortical bone thickness from computed tomography (CT) scans with metallic implants and to assess the benefits of metal artefact removal software. Methods A previously validated technique based on the fitting of a cortical model was modified to also model metal structures when required. Cortical thickness measurements were taken over intact bone segments and compared with the corresponding contralateral bone segment. The evaluation dataset includes post-operative CT scans of a unipolar hemi-arthroplasty, a dynamic hip screw fixation, a bipolar hemi-arthroplasty, a fixation with cannulated screws and a total hip arthroplasty. All CT scans were analysed before and after processing with metal artefact removal software. Results Cortical thickness validity and accuracy were improved through the use of a modified metalwork-optimised model and metal artefact removal software. For the proximal femoral segments of the aforementioned cases, the cortical thickness was measured with a mean absolute error of 0.55, 0.39, 0.46, 0.53 and 0.69 mm. The hemi-pelvis produced thickness errors of 0.51, 0.52, 0.52, 0.47 and 0.67 mm, respectively. Conclusions The proposed method was shown to measure cortical bone thickness in the presence of metalwork at a sub-millimetre accuracy. This new technique might be helpful in assessing fracture healing near implants or fixation devices, and improve the evaluation of periprosthetic bone after hip replacement surgery.This study was funded by Eli Lilly, Europe. TW, GMT, AHG and KESP received research grants from Eli Lilly. KESP is also funded by the Cambridge NIHR Biomedical Research Centre (BRC). The Evelyn Trust funded GMT

Cortical bone mapping: An application to hand and foot bones in hominoids

Bone form reflects both the genetic profile and behavioural history of an individual. As cortical bone is able to remodel in response to mechanical stimuli, interspecific differences in cortical bone thickness may relate to loading during locomotion or manual behaviours during object manipulation. Here, we test the application of a novel method of cortical bone mapping to the third metacarpal (Mc3) and talus of Pan, Pongo, and Homo. This method of analysis allows measurement of cortical thickness throughout the bone, and as such is applicable to elements with complex morphology. In addition, it allows for registration of each specimen to a canonical surface, and identifies regions where cortical thickness differs significantly between groups. Cortical bone mapping has potential for application to palaeoanthropological studies; however, due to the complexity of correctly registering homologous regions across varied morphology, further methodological development would be advantageous

Multilevel Resistance Switching and Enhanced Spin Transition Temperature in Single and Double Molecule Spin Crossover Nanogap Devices

Spin crossover (SCO) molecules are promising bi-stable magnetic switches with applications in molecular spintronics. However, little is known about the switching effects of a single SCO molecule when it is confined between two metal electrodes. Here we examine the switching properties of a [Fe(III)(EtOSalPet )(NCS)] SCO molecule that is specifically tailored for surface deposition and binding to only one gold electrode in a nanogap device. Temperature dependent conductivity measurements on SCO molecule containing electromigrated gold break junctions show voltage independent telegraphic-like switching between two resistance states at temperature below 200 K. The transition temperature is very different from the transition temperature of 83 K that occurs in a bulk film of the same material. This indicates that the bulk, co-operative SCO phenomenon is no longer preserved for a single molecule and that the surface interaction drastically increases the temperature of the SCO phenomenon. Another key finding of this work is that some devices show switching between multiple resistance levels. We propose that in this case, two SCO molecules are present within the nanogap with both participating in the electronic transport and switching

Focal osteoporosis defects play a key role in hip fracture

$\textbf{BACKGROUND}$: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. $\textbf{METHODS}$: The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. $\textbf{RESULTS}$: Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. $\textbf{CONCLUSION}$: Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.Arthritis Research UK (grant no. ARC17822) and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre