A Semi-Automated Workflow for FAIR Maturity Indicators in the Life Sciences.

Data sharing and reuse are crucial to enhance scientific progress and maximize return of investments in science. Although attitudes are increasingly favorable, data reuse remains difficult due to lack of infrastructures, standards, and policies. The FAIR (findable, accessible, interoperable, reusable) principles aim to provide recommendations to increase data reuse. Because of the broad interpretation of the FAIR principles, maturity indicators are necessary to determine the FAIRness of a dataset. In this work, we propose a reproducible computational workflow to assess data FAIRness in the life sciences. Our implementation follows principles and guidelines recommended by the maturity indicator authoring group and integrates concepts from the literature. In addition, we propose a FAIR balloon plot to summarize and compare dataset FAIRness. We evaluated the feasibility of our method on three real use cases where researchers looked for six datasets to answer their scientific questions. We retrieved information from repositories (ArrayExpress, Gene Expression Omnibus, eNanoMapper, caNanoLab, NanoCommons and ChEMBL), a registry of repositories, and a searchable resource (Google Dataset Search) via application program interfaces (API) wherever possible. With our analysis, we found that the six datasets met the majority of the criteria defined by the maturity indicators, and we showed areas where improvements can easily be reached. We suggest that use of standard schema for metadata and the presence of specific attributes in registries of repositories could increase FAIRness of datasets.

pyKNEEr: An image analysis workflow for open and reproducible research on femoral knee cartilage.

Transparent research in musculoskeletal imaging is fundamental to reliably investigate diseases such as knee osteoarthritis (OA), a chronic disease impairing femoral knee cartilage. To study cartilage degeneration, researchers have developed algorithms to segment femoral knee cartilage from magnetic resonance (MR) images and to measure cartilage morphology and relaxometry. The majority of these algorithms are not publicly available or require advanced programming skills to be compiled and run. However, to accelerate discoveries and findings, it is crucial to have open and reproducible workflows. We present pyKNEEr, a framework for open and reproducible research on femoral knee cartilage from MR images. pyKNEEr is written in python, uses Jupyter notebook as a user interface, and is available on GitHub with a GNU GPLv3 license. It is composed of three modules: 1) image preprocessing to standardize spatial and intensity characteristics; 2) femoral knee cartilage segmentation for intersubject, multimodal, and longitudinal acquisitions; and 3) analysis of cartilage morphology and relaxometry. Each module contains one or more Jupyter notebooks with narrative, code, visualizations, and dependencies to reproduce computational environments. pyKNEEr facilitates transparent image-based research of femoral knee cartilage because of its ease of installation and use, and its versatility for publication and sharing among researchers. Finally, due to its modular structure, pyKNEEr favors code extension and algorithm comparison. We tested our reproducible workflows with experiments that also constitute an example of transparent research with pyKNEEr, and we compared pyKNEEr performances to existing algorithms in literature review visualizations. We provide links to executed notebooks and executable environments for immediate reproducibility of our findings.

Assessment of Open Syndesmosis Reduction Techniques in an Unbroken Fibula Model: Visualization Versus Palpation.

OBJECTIVES: This cadaveric study sought to evaluate the accuracy of syndesmotic reduction using direct visualization via an anterolateral approach compared with palpation of the syndesmosis through a laterally based incision. METHODS: Ten cadaveric specimens were obtained and underwent baseline computed tomography (CT) scans. Subsequently, a complete syndesmotic injury was simulated by transecting the anterior inferior tibiofibular ligament, posterior inferior tibiofibular ligament, transverse ligament, interosseous membrane, and deltoid ligament. Three orthopaedic trauma surgeons were then asked to reduce each syndesmosis using direct visualization via an anterolateral approach. Specimens were then stabilized and underwent postreduction CT scans. Fixation was then removed, the anterolateral exposure was closed, and the surgeons were then asked to reduce the syndesmosis using palpation only via a direct lateral approach. Specimens were again instrumented and underwent postreduction CT scans. Two-tailed paired t tests were used to compare reductions with baseline scans with significance set at P < 0.05. RESULTS: There was no statistically significant difference between reduction via direct visualization or palpation via lateral approach when compared with baseline scans. Although measurements did not reach significance, there was a tendency toward external rotation, and anteromedial translation with direct visualization, and a trend toward fibular external rotation and posterolateral translation with palpation. CONCLUSIONS: There is no difference in reduction quality using direct visualization or palpation to assess the syndesmosis. Surgeons may therefore choose either technique when reducing syndesmotic injures based on personal preference and other injury factors.

Comparison of Different Approaches for Measuring Tibial Cartilage Thickness.

Osteoarthritis is a degenerative disease affecting bones and cartilage especially in the human knee. In this context, cartilage thickness is an indicator for knee cartilage health. Thickness measurements are performed on medical images acquired in-vivo. Currently, there is no standard method agreed upon that defines a distance measure in articular cartilage. In this work, we present a comparison of different methods commonly used in literature. These methods are based on nearest neighbors, surface normal vectors, local thickness and potential field lines. All approaches were applied to manual segmentations of tibia and lateral and medial tibial cartilage performed by experienced raters. The underlying data were contrast agent-enhanced cone-beam C-arm CT reconstructions of one healthy subject's knee. The subject was scanned three times, once in supine position and two times in a standing weight-bearing position. A comparison of the resulting thickness maps shows similar distributions and high correlation coefficients between the approaches above 0.90. The nearest neighbor method results on average in the lowest cartilage thickness values, while the local thickness approach assigns the highest values. We showed that the different methods agree in their thickness distribution. The results will be used for a future evaluation of cartilage change under weight-bearing conditions.

Quantifying sex, race, and age specific differences in bone microstructure requires measurement of anatomically equivalent regions.

INTRODUCTION: Individuals differ in forearm length. As microstructure differs along the radius, we hypothesized that errors may occur when sexual and racial dimorphisms are quantified at a fixed distance from the radio-carpal joint. METHODS: Microstructure was quantified ex vivo in 18 cadaveric radii using high resolution peripheral quantitative computed tomography and in vivo in 158 Asian and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI positioned at 4.5-6% of forearm length and using the fixed ROI adjusted for cross sectional area (CSA), forearm length or height. Secular effects of age were assessed by comparing 38 younger and 33 older women. RESULTS: Ex vivo, similar amounts of bone mass fashioned adjacent cross sections. Larger distal cross sections had thinner porous cortices of lower matrix mineral density (MMD), a larger medullary CSA and higher trabecular density. Smaller proximal cross-sections had thicker less porous cortices of higher MMD, a small medullary canal with little trabecular bone. Taller persons had more distally positioned fixed ROIs which moved proximally when corrected. Shorter persons had more proximally positioned fixed ROIs which moved distally when corrected, so dimorphisms lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25 SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and trabecular density. Results were similar using an adjusted fixed ROI. Adjusting for secular effects of age on forearm length resulted in the age-related increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). CONCLUSION: Assessment of sex, race and age related differences in microstructure requires measurement of anatomically equivalent regions.

Statistical Parametric Mapping of HR-pQCT Images: A Tool for Population-Based Local Comparisons of Micro-Scale Bone Features.

HR-pQCT enables in vivo multi-parametric assessments of bone microstructure in the distal radius and distal tibia. Conventional HR-pQCT image analysis approaches summarize bone parameters into global scalars, discarding relevant spatial information. In this work, we demonstrate the feasibility and reliability of statistical parametric mapping (SPM) techniques for HR-pQCT studies, which enable population-based local comparisons of bone properties. We present voxel-based morphometry (VBM) to assess trabecular and cortical bone voxel-based features, and a surface-based framework to assess cortical bone features both in cross-sectional and longitudinal studies. In addition, we present tensor-based morphometry (TBM) to assess trabecular and cortical bone structural changes. The SPM techniques were evaluated based on scan-rescan HR-pQCT acquisitions with repositioning of the distal radius and distal tibia of 30 subjects. For VBM and surface-based SPM purposes, all scans were spatially normalized to common radial and tibial templates, while for TBM purposes, rescans (follow-up) were spatially normalized to their corresponding scans (baseline). VBM was evaluated based on maps of local bone volume fraction (BV/TV), homogenized volumetric bone mineral density (vBMD), and homogenized strain energy density (SED) derived from micro-finite element analysis; while the cortical bone framework was evaluated based on surface maps of cortical bone thickness, vBMD, and SED. Voxel-wise and vertex-wise comparisons of bone features were done between the groups of baseline and follow-up scans. TBM was evaluated based on mean square errors of determinants of Jacobians at baseline bone voxels. In both anatomical sites, voxel- and vertex-wise uni- and multi-parametric comparisons yielded non-significant differences, and TBM showed no artefactual bone loss or apposition. The presented SPM techniques demonstrated robust specificity thus warranting their application in future clinical HR-pQCT studies.

Automatic multi-parametric quantification of the proximal femur with quantitative computed tomography.

BACKGROUND: Quantitative computed tomography (QCT) imaging is the basis for multiple assessments of bone quality in the proximal femur, including volumetric bone mineral density (vBMD), tissue volume, estimation of bone strength using finite element modeling (FEM), cortical bone thickness, and computational-anatomy-based morphometry assessments. METHODS: Here, we present an automatic framework to perform a multi-parametric QCT quantification of the proximal femur. In this framework, the proximal femur is cropped from the bilateral hip scans, segmented using a multi-atlas based segmentation approach, and then assigned volumes of interest through the registration of a proximal femoral template. The proximal femur is then subjected to compartmental vBMD, compartmental tissue volume, FEM bone strength, compartmental surface-based cortical bone thickness, compartmental surface-based vBMD, local surface-based cortical bone thickness, and local surface-based cortical vBMD computations. Consequently, the template registrations together with vBMD and surface-based cortical bone parametric maps enable computational anatomy studies. The accuracy of the segmentation was validated against manual segmentations of 80 scans from two clinical facilities, while the multi-parametric reproducibility was evaluated using repeat scans with repositioning from 22 subjects obtained on CT imaging systems from two manufacturers. RESULTS: Accuracy results yielded a mean dice similarity coefficient of 0.976±0.006, and a modified Haussdorf distance of 0.219±0.071 mm. Reproducibility of QCT-derived parameters yielded root mean square coefficients of variation (CVRMS) between 0.89-1.66% for compartmental vBMD; 0.20-1.82% for compartmental tissue volume; 3.51-3.59% for FEM bone strength; 1.89-2.69% for compartmental surface-based cortical bone thickness; and 1.08-2.19% for compartmental surface-based cortical vBMD. For local surface-based assessments, mean CVRMS were between 3.45-3.91% and 2.74-3.15% for cortical bone thickness and vBMD, respectively. CONCLUSIONS: The automatic framework presented here enables accurate and reproducible QCT multi-parametric analyses of the proximal femur. Our subjects were elderly, with scans obtained across multiple clinical sites and manufacturers, thus documenting its value for clinical trials and other multi-site studies.

Image-based vs. mesh-based statistical appearance models of the human femur: implications for finite element simulations.

Statistical appearance models have recently been introduced in bone mechanics to investigate bone geometry and mechanical properties in population studies. The establishment of accurate anatomical correspondences is a critical aspect for the construction of reliable models. Depending on the representation of a bone as an image or a mesh, correspondences are detected using image registration or mesh morphing. The objective of this study was to compare image-based and mesh-based statistical appearance models of the femur for finite element (FE) simulations. To this aim, (i) we compared correspondence detection methods on bone surface and in bone volume; (ii) we created an image-based and a mesh-based statistical appearance models from 130 images, which we validated using compactness, representation and generalization, and we analyzed the FE results on 50 recreated bones vs. original bones; (iii) we created 1000 new instances, and we compared the quality of the FE meshes. Results showed that the image-based approach was more accurate in volume correspondence detection and quality of FE meshes, whereas the mesh-based approach was more accurate for surface correspondence detection and model compactness. Based on our results, we recommend the use of image-based statistical appearance models for FE simulations of the femur.

Inter-scanner differences in in vivo QCT measurements of the density and strength of the proximal femur remain after correction with anthropomorphic standardization phantoms.

In multicenter studies and longitudinal studies that use two or more different quantitative computed tomography (QCT) imaging systems, anthropomorphic standardization phantoms (ASPs) are used to correct inter-scanner differences and allow pooling of data. In this study, in vivo imaging of 20 women on two imaging systems was used to evaluate inter-scanner differences in hip integral BMD (iBMD), trabecular BMD (tBMD), cortical BMD (cBMD), femoral neck yield moment (My) and yield force (Fy), and finite-element derived strength of the femur under stance (FEstance) and fall (FEfall) loading. Six different ASPs were used to derive inter-scanner correction equations. Significant (p<0.05) inter-scanner differences were detected in all measurements except My and FEfall, and no ASP-based correction was able to reduce inter-scanner variability to corresponding levels of intra-scanner precision. Inter-scanner variability was considerably higher than intra-scanner precision, even in cases where the mean inter-scanner difference was statistically insignificant. A significant (p<0.01) effect of body size on inter-scanner differences in BMD was detected, demonstrating a need to address the effects of body size on QCT measurements. The results of this study show that significant inter-scanner differences in QCT-based measurements of BMD and bone strength can remain even when using an ASP.

The virtual skeleton database: an open access repository for biomedical research and collaboration.

BACKGROUND: Statistical shape models are widely used in biomedical research. They are routinely implemented for automatic image segmentation or object identification in medical images. In these fields, however, the acquisition of the large training datasets, required to develop these models, is usually a time-consuming process. Even after this effort, the collections of datasets are often lost or mishandled resulting in replication of work. OBJECTIVE: To solve these problems, the Virtual Skeleton Database (VSD) is proposed as a centralized storage system where the data necessary to build statistical shape models can be stored and shared. METHODS: The VSD provides an online repository system tailored to the needs of the medical research community. The processing of the most common image file types, a statistical shape model framework, and an ontology-based search provide the generic tools to store, exchange, and retrieve digital medical datasets. The hosted data are accessible to the community, and collaborative research catalyzes their productivity. RESULTS: To illustrate the need for an online repository for medical research, three exemplary projects of the VSD are presented: (1) an international collaboration to achieve improvement in cochlear surgery and implant optimization, (2) a population-based analysis of femoral fracture risk between genders, and (3) an online application developed for the evaluation and comparison of the segmentation of brain tumors. CONCLUSIONS: The VSD is a novel system for scientific collaboration for the medical image community with a data-centric concept and semantically driven search option for anatomical structures. The repository has been proven to be a useful tool for collaborative model building, as a resource for biomechanical population studies, or to enhance segmentation algorithms.

Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development.

Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database.48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit.