Morphology-based Noise Reduction: Structural Variation and Thresholding in the Bitonic Filter

The bitonic filter was recently developed to embody the novel concept of signal bitonicity (one local extremum within a set range) to differentiate from noise, by use of data ranking and linear operators. For processing images, the spatial extent was locally constrained to a fixed circular mask. Since structure in natural images varies, a novel structurally varying bitonic filter is presented, which locally adapts the mask, without following patterns in the noise. This new filter includes novel robust structurally varying morphological operations, with efficient implementations, and a novel formulation of non-iterative directional Gaussian filtering. Data thresholds are also integrated with the morphological operations, increasing noise reduction for low noise, and enabling a multi-resolution framework for high noise levels. The structurally varying bitonic filter is presented without presuming prior knowledge of morphological filtering, and compared to high-performance linear noise-reduction filters, to set this novel concept in context. These are tested over a wide range of noise levels, on a fairly broad set of images. The new filter is a considerable improvement on the fixed-mask bitonic, outperforms anisotropic diffusion and image-guided filtering in all but extremely low noise, non-local means at all noise levels, but not the block-matching 3D filter, though results are promising for very high noise. The structurally varying bitonic tends to have less characteristic residual noise in regions of smooth signal, and very good preservation of signal edges, though with some loss of small scale detail when compared to the block-matching 3D filter. The efficient implementation means that processing time, though slower than the fixed-mask bitonic filter, remains competitive

The Bitonic Filter: Linear Filtering in an Edge-preserving Morphological Framework.

A new filter is presented which has better edge and detail preserving properties than a median, noise reduction capability similar to a Gaussian, and is applicable to many signal and noise types. It is built on a definition of signal as bitonic, i.e. containing only one local maxima or minima within the filter range. This definition is based on data ranking rather than value, hence the bitonic filter comprises a combination of non-linear morphological and linear operators. It has no data-level-sensitive parameters and can locally adapt to the signal and noise levels in an image, precisely preserving both smooth and discontinuous signals of any level when there is no noise, but also reducing noise in other areas without creating additional artefactual noise. Both the basis and the performance of the filter are examined in detail, and it is shown to be a significant improvement on the Gaussian and median. It is also compared over various noisy images to the image-guided filter, anisotropic diffusion, non-local means, the grain filter, and self-dual forms of levelling and rank filters. In terms of signal-to-noise, the bitonic filter outperforms all these except non-local means, and sometimes anisotropic diffusion. However it gives good visual results in all circumstances, with characteristics which make it appropriate particularly for signals or images with varying noise, or features at varying levels. The bitonic has very few parameters, does not require optimisation nor prior knowledge of noise levels, does not have any problems with stability, and is reasonably fast to implement. Despite its non-linearity, it hence represents a very practical operation with general applicability

Systematic misregistration and the statistical analysis of surface data.

Spatial normalisation is a key element of statistical parametric mapping and related techniques for analysing cohort statistics on voxel arrays and surfaces. The normalisation process involves aligning each individual specimen to a template using some sort of registration algorithm. Any misregistration will result in data being mapped onto the template at the wrong location. At best, this will introduce spatial imprecision into the subsequent statistical analysis. At worst, when the misregistration varies systematically with a covariate of interest, it may lead to false statistical inference. Since misregistration generally depends on the specimen's shape, we investigate here the effect of allowing for shape as a confound in the statistical analysis, with shape represented by the dominant modes of variation observed in the cohort. In a series of experiments on synthetic surface data, we demonstrate how allowing for shape can reveal true effects that were previously masked by systematic misregistration, and also guard against misinterpreting systematic misregistration as a true effect. We introduce some heuristics for disentangling misregistration effects from true effects, and demonstrate the approach's practical utility in a case study of the cortical bone distribution in 268 human femurs.This is the author’s version of a work that was accepted for publication in Medical Image Analysis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Medical Image Analysis, [Volume 18, Issue 2, February 2014] DOI http://dx.doi.org/10.1016/j.media.2013.12.007

Practicable assessment of cochlear size and shape from clinical CT images

There is considerable interpersonal variation in the size and shape of the human cochlea, with evident consequences for cochlear implantation. The ability to characterize a specific cochlea, from preoperative computed tomography (CT) images, would allow the clinician to personalize the choice of electrode, surgical approach and postoperative programming. In this study, we present a fast, practicable and freely available method for estimating cochlear size and shape from clinical CT. The approach taken is to fit a template surface to the CT data, using either a statistical shape model or a locally affine deformation (LAD). After fitting, we measure cochlear size, duct length and a novel measure of basal turn non-planarity, which we suggest might correlate with the risk of insertion trauma. Gold-standard measurements from a convenience sample of 18 micro-CT scans are compared with the same quantities estimated from low-resolution, noisy, pseudo-clinical data synthesized from the same micro-CT scans. The best results were obtained using the LAD method, with an expected error of 8-17% of the gold-standard sample range for non-planarity, cochlear size and duct length.Evelyn Trust, MRC Confidence in Concept Fund Cambridge Hearing Trust

Mapping Bone Changes at the Proximal Femoral Cortex of Postmenopausal Women in Response to Alendronate and Teriparatide Alone, Combined or Sequentially.

Combining antiresorptive and anabolic drugs for osteoporosis may be a useful strategy to prevent hip fractures. Previous studies comparing the effects of alendronate (ALN) and teriparatide (TPTD) alone, combined or sequentially using quantitative computed tomography (QCT) in postmenopausal women have not distinguished cortical bone mineral density (CBMD) from cortical thickness (CTh) effects, nor assessed the distribution and extent of more localized changes. In this study a validated bone mapping technique was used to examine the cortical and endocortical trabecular changes in the proximal femur resulting from an 18-month course of ALN or TPTD. Using QCT data from a different clinical trial, the global and localized changes seen following a switch to TPTD after an 18-month ALN treatment or adding TPTD to the ALN treatment were compared. Ct.Th increased (4.8%, p < 0.01) and CBMD decreased (-4.5%, p < 0.01) in the TPTD group compared to no significant change in the ALN group. A large Ct.Th increase could be seen for the switch group (2.8%, p < 0.01) compared to a significantly smaller increase for the add group (1.5%, p < 0.01). CBMD decreased significantly for the switch group (-3.9%, p < 0.01) and was significantly different from no significant change in the add group. Ct.Th increases were shown to be significantly greater for the switch group compared to the add group at the load bearing regions. This study provides new insights into the effects of ALN and TPTD combination therapies on the cortex of the proximal femur and supports the hypothesis of an increased bone remodeling by TPTD being mitigated by ALN.This is the accepted manuscript. The final version is available at http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2454/abstract

The Effects on the Femoral Cortex of a 24 Month Treatment Compared to an 18 Month Treatment with Teriparatide: A Multi-Trial Retrospective Analysis.

BACKGROUND: Teriparatide (TPTD) is an anabolic agent indicated for the treatment of severely osteoporotic patients who are at high risk of fragility fractures. The originally approved duration of TPTD treatment in several regions, including Europe, was 18 months. However, studies of areal bone mineral density (aBMD) showed additional benefit when treatment is continued beyond 18 months, and the drug is currently licenced for 24 months. Improvements in cortical structure at the proximal femur have already been shown in patients given TPTD for 24 months using quantitative computed tomography (QCT). Here, we investigate whether cortical and endocortical trabecular changes differ between an 18- and 24-month treatment. METHODS: Since an 18- versus 24-month TPTD study using QCT has not been conducted, we studied combined QCT data from four previous clinical trials. Combined femoral QCT data from three 18-month TPTD studies ('18-month group') were compared with data from a fourth 24-month trial ('24-month group'). Cortical parameters were measured over the entire proximal femur which allowed for a comparison of the mean changes as well as a visual comparison of the colour maps of changes after 18 and 24 months TPTD. RESULTS: For both the combined 18-month group and the 24-month group, overall cortical thickness and endocortical trabecular density increased, while overall cortical bone mineral density decreased. While the changes in the 24-month group were of greater magnitude compared to the 18-month group, the differences were only significant for the endocortical trabecular density (ECTD), corrected for age, weight, femoral neck T-score, total hip T-score and the baseline mean ECTD. CONCLUSION: Although the combination of data from different clinical trials is not optimal, these data support the concept that the duration of TPTD in the 18-24 month phase is of clinical relevance when considering improvement in hip structure.This study was funded by Eli Lilly. TW, GMT, AHG and KESP received research grants from Eli Lilly. KESP is also funded by the Cambridge NIHR Biomedical research Centre. The Evelyn Trust funded GMT. The funders had no role in study design, data analysis or decision to publish, but were involved in collection of data and had the chance to review the manuscript once written.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014772

Quantitative 3D analysis of bone in hip osteoarthritis using clinical computed tomography.

OBJECTIVE: To assess the relationship between proximal femoral cortical bone thickness and radiological hip osteoarthritis using quantitative 3D analysis of clinical computed tomography (CT) data. METHODS: Image analysis was performed on clinical CT imaging data from 203 female volunteers with a technique called cortical bone mapping (CBM). Colour thickness maps were created for each proximal femur. Statistical parametric mapping was performed to identify statistically significant differences in cortical bone thickness that corresponded with the severity of radiological hip osteoarthritis. Kellgren and Lawrence (K&L) grade, minimum joint space width (JSW) and a novel CT-based osteophyte score were also blindly assessed from the CT data. RESULTS: For each increase in K&L grade, cortical thickness increased by up to 25 % in distinct areas of the superolateral femoral head-neck junction and superior subchondral bone plate. For increasing severity of CT osteophytes, the increase in cortical thickness was more circumferential, involving a wider portion of the head-neck junction, with up to a 7 % increase in cortical thickness per increment in score. Results were not significant for minimum JSW. CONCLUSIONS: These findings indicate that quantitative 3D analysis of the proximal femur can identify changes in cortical bone thickness relevant to structural hip osteoarthritis. KEY POINTS: • CT is being increasingly used to assess bony involvement in osteoarthritis • CBM provides accurate and reliable quantitative analysis of cortical bone thickness • Cortical bone is thicker at the superior femoral head-neck with worse osteoarthritis • Regions of increased thickness co-locate with impingement and osteophyte formation • Quantitative 3D bone analysis could enable clinical disease prediction and therapy development.TT acknowledges the support of an Evelyn Trust Clinical Training Fellowship award (RG65411). KP acknowledges support of an Arthritis Research UK Research Progression award (RG66087), and the Cambridge NIHR Biomedical Research Centre (RG64245). None of the funding sources had a role in study design, data handling, writing of the report, or decision to submit the paper for publication.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00330-015-4048-

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

Targeted regeneration of bone in the osteoporotic human femur.

We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness

Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis.

Women with osteoporosis treated for 36 months with twice-yearly injections of denosumab sustained fewer hip fractures compared with placebo. Treatment might improve femoral bone at locations where fractures typically occur. To test this hypothesis, we used 3D cortical bone mapping of postmenopausal women with osteoporosis to investigate the timing and precise location of denosumab versus placebo effects in the hips. We analyzed clinical computed tomography scans from 80 female participants in FREEDOM, a randomized trial, wherein half of the study participants received subcutaneous denosumab 60 mg twice yearly and the others received placebo. Cortical 3D bone thickness maps of both hips were created from scans at baseline, 12, 24, and 36 months. Cortical mass surface density maps were also created for each visit. After registration of each bone to an average femur shape model followed by statistical parametric mapping, we visualized and quantified statistically significant treatment effects. The technique allowed us to pinpoint systematic differences between denosumab and control and to display the results on a 3D average femur model. Denosumab treatment led to an increase in femoral cortical mass surface density and thickness, already evident by the third injection (12 months). Overall, treatment with denosumab increased femoral cortical mass surface density by 5.4% over 3 years. One-third of the increase came from increasing cortical density, and two-thirds from increasing cortical thickness, relative to placebo. After 36 months, cortical mass surface density and thickness had increased by up to 12% at key locations such as the lateral femoral trochanter versus placebo. Most of the femoral cortex displayed a statistically significant relative difference by 36 months. Osteoporotic cortical bone responds rapidly to denosumab therapy, particularly in the hip trochanteric region. This mechanism may be involved in the robust decrease in hip fractures observed in denosumab-treated women at increased risk of fracture.This study was funded by Amgen Inc., Thousand Oaks, CA, USA. Cambridge Bone Group is supported by Arthritis Research UK, The Evelyn Trust, and Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.232