Three-dimensional design optimisation of patient-specific femoral plates as a means of bone remodelling reduction

Previous investigations into the optimisation of internal plates have mostly focused on the material properties of the implant. In this work, we optimise the shape, size and placement of the plate for successfully minimising bone remodelling around the implant. A design optimisation algorithm based on strain energy density criterion, combined with the finite element analysis, has been used in this study. The main optimisation goal was to reduce this change and keep it close to the conditions of an intact femur. The results suggest that the anterolateral side of the bone would be the optimum location for the plate, as for the geometry, the optimum moves towards having a thick, wide and short plate. These important results could be directly applicable to orthopaedic surgeons treating a femur fracture with internal plates. Since the optimisation algorithm remains the same for any patient, this advancement provides the surgeon with a tool to minimise the post surgery remodelling by trying to maintain the natural structure of the bone.     

Design of an implant for first metatarsophalangeal hemi-arthroplasty

This study was designed to examine the three-dimensional geometry of the head of the first metatarsal bone of the foot. Ninety-seven adult first metatarsal head (MTH1) bones were scanned using a laser scanner at 400 dpi. A best-fit ellipsoid was obtained from the articular surfaces of MTH1 for each size group using nonlinear unconstrained optimisation. Average root mean square errors between the articulating surfaces and the optimal fit surfaces of the bone specimens were between 0.29 and 0.42 mm. After classification based on sex and size groups, the profile provided a good fit to individual bones. Consideration of the thickness of cartilage overlying the metatarsal head (MTH) may further improve the fit. The proposed approach provides the basis for a design of an MTH hemi-arthroplasty that has good anatomical congruence with the native joint.     

Registration of 2D histological sections with 3D micro-CT datasets from small animal vertebrae and tibiae

The aim of this study was the registration of digitized thin 2D sections of mouse vertebrae and tibiae used for histomorphometry of trabecular bone structure into 3D micro computed tomography (μCT) datasets of the samples from which the sections were prepared. Intensity-based and segmentation-based registrations (SegRegs) of 2D sections and 3D μCT datasets were applied. As the 2D sections were deformed during their preparation, affine registration for the vertebrae was used instead of rigid registration. Tibiae sections were additionally cut on the distal end, which subsequently undergone more deformation so that elastic registration was necessary. The Jaccard distance was used as registration quality measure. The quality of intensity-based registrations and SegRegs was practically equal, although precision errors of the elastic registration of segmentation masks in tibiae were lower, while those in vertebrae were lower for the intensity-based registration. Results of SegReg significantly depended on the segmentation of the μCT datasets. Accuracy errors were reduced from approximately 64% to 42% when applying affine instead of rigid transformations for the vertebrae and from about 43% to 24% when using B-spline instead of rigid transformations for the tibiae. Accuracy errors can also be caused by the difference in spatial resolution between the thin sections (pixel size: 7.25 μm) and the μCT data (voxel size: 15 μm). In the vertebrae, average deformations amounted to a 6.7% shortening along the direction of sectioning and a 4% extension along the perpendicular direction corresponding to 0.13–0.17 mm. Maximum offsets in the mouse tibiae were 0.16 mm on average.     

Anatomical Feature Segmentation of Femur Point Cloud Based on Medical Semantics

Feature segmentation is an essential phase for geometric modeling and shape processing in anatomical study of human skeleton and clinical digital treatment of orthopedics. Due to various degrees of freedom of bone surface, the existing segmentation algorithms can hardly meet specific medical need. To address this, a novel segmentation methodology for anatomical features of femur model based on medical semantics is put forward. First, anatomical reference objects (ARO) are created to represent typical characteristics of femur anatomy by 3D point fitting in combination with medical priori knowledge. Then, local point clouds between adjacent anatomies are selected according to the AROs to extract boundary feature point (BFP)s. Finally, the complete model of femur is divided into anatomical regions by executing the enhanced watershed algorithm guided with BFPs. Experimental results show that the proposed method has the advantages of automatic segmentation of femoral head, neck and other complex areas, and the segmentation results have better medical semantics. In addition, the slight modification of segmentation results can be achieved by adjusting a few threshold parameter values, which improves the convenience of modification for ordinary users.     

1,25-Dihydroxyvitamin D3 decreases alkaline phosphatase activity in cultures of embryonic chick tibiae

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the alkaline phosphatase (AlPase) activity in cultures of chick embryo tibiae was determined. A dose-related, decreased release (30-47%) of AlPase from the bones was seen with the metabolite at 0.05-0.5 ng/ml of medium with a similar effect on the bone content of enzyme. The highest dose (1 ng/ml) decreased the bone content by 38% without further effect on AlPase release. Combining a low level of 1,25(OH)2D3 (0.05 ng/ml) with parathyroid hormone (PTH, 1 U/ml) reduced release of enzyme additively, but caused no greater decrease in bone content of activity than PTH alone. No effects of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3, 0.5 ng/ml] on release or bone content of AlPase were found when this metabolite was added alone or in combination with PTH; however, 24,25(OH)2D3 did prevent the inhibition of release of AlPase when added with 1,25(OH)2D3. After a 1-day exposure to 1,25(OH)2D3, continued incubation in metabolite-free medium resulted in an 89% increase in bone content of AlPase. The results suggest that 1,25(OH)2D3, as well as PTH, may have regulatory roles in bone growth through their effects on AlPase.     

The mesh-matching algorithm: an automatic 3D mesh generator for finite element structures

Several authors have employed finite element analysis for stress and strain analysis in orthopaedic biomechanics. Unfortunately, the definition of three-dimensional models is time consuming (mainly because of the manual 3D meshing process) and consequently the number of analyses to be performed is limited. The authors have investigated a new patient-specific method allowing automatically 3D mesh generation for structures as complex as bone for example. This method, called the mesh-matching (M-M) algorithm, generated automatically customized 3D meshes of anatomical structures from an already existing model. The M-M algorithm has been used to generate FE models of 10 proximal human femora from an initial one which had been experimentally validated. The automatically generated meshes seemed to demonstrate satisfying results.     

Effects of weightlessness on osseous tissue of the rat after a space flight of 5 days (Cosmos 1514)

Five pregnant female growing rats have been orbited for five days aboard the Cosmos 1514 soviet biological satellite. They were compared to five female rats kept in vivarium and five female conditioned rats in synchronised way. Histomorphometric studies were performed in order to investigate: 1. The early effects of weightlessness on the bone mass in loading (tibiae and femur) and unloading bones (thoracic and lumbar vertebrae). 2. The changes of osteoblastic and osteoclastic activities. A short exposure does not induce changes in the bone mass and the inner structure of loading and unloading bones. These results fit in well with human data available in the literature: they show that weightlessness doesn't change bone mass in the early phase of a spaceflight. However extrapolation of animal results to men is discussed. In unloading bones (vertebrae) osteoblastic activity was not measurable. Osteoclasts detected by histoenzymologic method don't change as far as their number per mm3 of trabecular bone is concerned. However the number per mm2 of trabecular area increases. It seems likely that an increase of the osteoclastic population occurs in trabecular bone. In loading bones, formation activity (appreciated by the measurement of osteoid seam thickness) and total osteoclastic resorption surfaces were not modified. These results are different from those of longer flights.     

A 3D Network Based Shape Prior for Automatic Myocardial Disease Segmentation in Delayed-Enhancement MRI

Objectives: In this work, a new deep learning model for relevant myocardial infarction segmentation from Late Gadolinium Enhancement (LGE)-MRI is proposed. Moreover, our novel segmentation method aims to detect microvascular-obstructed regions accurately. Material and methods: We first segment the anatomical structures, i.e., the left ventricular cavity and the myocardium, to achieve a preliminary segmentation. Then, a shape prior based framework that fuses the 3D U-Net architecture with 3D Autoencoder segmentation framework to constrain the segmentation process of pathological tissues is applied. Results: The proposed network reached outstanding myocardial segmentation compared with the human-level performance with the average Dice score of ‘0.9507’ for myocardium, ‘0.7656’ for scar, and ‘0.8377’ for MVO on the validation set consisting of 16 DE-MRI volumes selected from the training EMIDEC dataset. Conclusion: It is concluded that our approach's extensive validation and comprehensive comparison against existing state-of-the-art deep learning models on three annotated datasets, including healthy and diseased exams, make this proposal a reliable tool to enhance MI diagnosis.     

Chondrocyte apoptosis enhanced at the growth plate: a physeal response to a diaphyseal fracture

Post-traumatic overgrowth of growing long bones is a common clinical phenomenon in paediatric traumatology and is the result of an enhanced stimulation of the nearby growth plate after fracture. To date, the exact post-fractural reactions of the growth plate are poorly understood. The aim of this study has been to determine the impact of fracture on the frequency of chondrocyte apoptosis of the growth plate. Rats sustained a mid-diaphyseal closed fracture of the left tibia or were left untreated. All animals were killed 3, 10, 14 or 29 days after trauma. The left and right tibiae were harvested and apoptotic chondrocytes of the proximal tibial growth plate were detected by TUNEL staining. The apoptosis percentage of physeal chondrocytes was statistically compared among fractured bones, intact contra-lateral bones and control bones. The physeal apoptosis rate of the fractured bone was significantly higher than that of the contra-lateral intact bone (valid for all evaluated days) and the control bone (valid from day 10 onwards). Contra-lateral intact tibiae never showed significantly higher apoptosis rates compared with control tibiae. Thus, mid-diaphyseal fracture influences the nearby growth plate by stimulating chondrocyte programmed cell death, which is associated with cartilage resorption and bone replacement. The lack of a significant difference between the intact contra-lateral and the intact control bone suggests that fracture only has a local effect that contributes to the greater apoptosis rate of the adjacent physis.     

Site specific bone adaptation response to mechanical loading

Over 25 million Americans suffer from osteoporosis. Bone size and strength depends both upon the level of adaptation due to physical activity (applied load), and genetics. We hypothesized that bone adaptation to loads differs among mice breeds and bone sites. Forty-five adult female mice from three inbred strains (C57BL/6 [B6], C3H/HeJ [C3], and DBA/2J [D2]) were loaded at the right tibia and ulna in vivo with non-invasive loading devices. Each loading session consisted of 99 cycles at a force range that induced approximately 2000 microstrain (microepsilon) at the mid-shaft of the tibia (2.5 to 3.5 N force) and ulna (1.5 to 2 N force). The right and left ulnae and tibiae were collected and processed using protocols for histological undecalcified cortical bone slides. Standard histomorphometry techniques were used to quantify new bone formation. The histomorphometric variables include percentage mineralizing surface (%MS), mineral apposition rate (MAR), and bone formation rate (BFR). Net loading response [right-left limb] was compared between different breeds at tibial and ulnar sites using two-way ANOVA with repeated measures (p<0.05). Significant site differences in bone adaptation response were present within each breed (p<0.005). In all the three breeds, the tibiae showed greater percentage MS, MAR and BFR than the ulna at similar in vivo load or mechanical stimulus (strain). These data suggest that the bone formation due to loading is greater in the tibiae than the ulnae. Although, no significant breed-related differences were found in response to loading, the data show greater trends in tibial bone response in B6 mice as compared to D2 and C3 mice. Our data indicate that there are site-specific skeletal differences in bone adaptation response to similar mechanical stimulus.     

The effect of active vitamin D3 analogs and dexamethasone on the expression of osteocalcin gene in rat tibiae in vivo.

We tested the effects of 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 2 beta-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 (ED-71) and dexamethasone on osteocalcin mRNA levels in rat tibiae in vivo. Northern blot analysis showed that both 1,25-(OH)2D3 and ED-71 caused an increase in osteocalcin mRNA levels in bone: 1,25-(OH)2D3 induced a transient increase in the mRNA levels followed by a decrease in the control level by 12 h post administration. In contrast, ED-71 caused a persistent increase in osteocalcin mRNA level for seven days post administration. Serum osteocalcin levels paralleled the osteocalcin mRNA level in bone in both groups. Dexamethasone caused a marked reduction in both osteocalcin mRNA and serum osteocalcin levels. Suppressive effect of dexamethasone on osteocalcin expression was persistent for seven days at higher dose. Our results represent the first demonstration of the effect of active vitamin D and corticosteroid on the expression of osteocalcin mRNA in bone in vivo.     

A new approach for assigning bone material properties from CT images into finite element models

Generation of subject-specific finite element (FE) models from computed tomography (CT) datasets is of significance for application of the FE analysis to bone structures. A great challenge that remains is the automatic assignment of bone material properties from CT Hounsfield Units into finite element models. This paper proposes a new assignment approach, in which material properties are directly assigned to each integration point. Instead of modifying the dataset of FE models, the proposed approach divides the assignment procedure into two steps: generating the data file of the image intensity of a bone in a MATLAB program and reading the file into ABAQUS via user subroutines. Its accuracy has been validated by assigning the density of a bone phantom into a FE model. The proposed approach has been applied to the FE model of a sheep tibia and its applicability tested on a variety of element types. The proposed assignment approach is simple and illustrative. It can be easily modified to fit users’ situations.     

ShapeRotator: An R tool for standardized rigid rotations of articulated three‐dimensional structures with application for geometric morphometrics

The quantification of complex morphological patterns typically involves comprehensive shape and size analyses, usually obtained by gathering morphological data from all the structures that capture the phenotypic diversity of an organism or object. Articulated structures are a critical component of overall phenotypic diversity, but data gathered from these structures are difficult to incorporate into modern analyses because of the complexities associated with jointly quantifying 3D shape in multiple structures. While there are existing methods for analyzing shape variation in articulated structures in two‐dimensional (2D) space, these methods do not work in 3D, a rapidly growing area of capability and research. Here, we describe a simple geometric rigid rotation approach that removes the effect of random translation and rotation, enabling the morphological analysis of 3D articulated structures. Our method is based on Cartesian coordinates in 3D space, so it can be applied to any morphometric problem that also uses 3D coordinates (e.g., spherical harmonics). We demonstrate the method by applying it to a landmark‐based dataset for analyzing shape variation using geometric morphometrics. We have developed an R tool (ShapeRotator) so that the method can be easily implemented in the commonly used R package geomorph and MorphoJ software. This method will be a valuable tool for 3D morphological analyses in articulated structures by allowing an exhaustive examination of shape and size diversity.     

Modelling external bone adaptation using evolutionary structural optimisation

External remodelling is significant in the bone healing process, and it is essential to predict the bone external shape in the design of artificial bone grafts. This paper demonstrates the effectiveness of the evolutionary structural optimisation (ESO) method for the simulation of bone morphology. A two-dimensional ESO strategy is developed which is capable of finding the modified bone topology beginning with any geometry under any loading conditions. The morphology of bone structure is described by the quantitative bone adaptation theory, which is integrated with the finite element method. The evolutionary topology optimisation process is introduced to find the bone shape. A rectangle, which occupies a larger space than the external shape of the bone structure, is specified as a design domain; the evolutionary process iteratively eliminates and redistributes material throughout the domain to obtain an optimum arrangement of bone materials. The technique has been tested on a wide range of examples. In this paper, the formation of trabecular bone architecture around an implant is studied; as another example, the growth of the coronal section of a vertebral body is predicted. The examples support the assertion that the external shape of bone structure can be successfully predicted by the proposed ESO procedure.     

Prediction of femoral strength using 3D finite element models reconstructed from DXA images: validation against experiments

Computed tomography (CT)-based finite element (FE) models may improve the current osteoporosis diagnostics and prediction of fracture risk by providing an estimate for femoral strength. However, the need for a CT scan, as opposed to the conventional use of dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnostics, is considered a major obstacle. The 3D shape and bone mineral density (BMD) distribution of a femur can be reconstructed using a statistical shape and appearance model (SSAM) and the DXA image of the femur. Then, the reconstructed shape and BMD could be used to build FE models to predict bone strength. Since high accuracy is needed in all steps of the analysis, this study aimed at evaluating the ability of a 3D FE model built from one 2D DXA image to predict the strains and fracture load of human femora. Three cadaver femora were retrieved, for which experimental measurements from ex vivo mechanical tests were available. FE models were built using the SSAM-based reconstructions: using only the SSAM-reconstructed shape, only the SSAM-reconstructed BMD distribution, and the full SSAM-based reconstruction (including both shape and BMD distribution). When compared with experimental data, the SSAM-based models predicted accurately principal strains (coefficient of determination >0.83, normalized root-mean-square error <16%) and femoral strength (standard error of the estimate 1215 N). These results were only slightly inferior to those obtained with CT-based FE models, but with the considerable advantage of the models being built from DXA images. In summary, the results support the feasibility of SSAM-based models as a practical tool to introduce FE-based bone strength estimation in the current fracture risk diagnostics.     

Quantitative comparison of freeware software for bone mesh from DICOM files

Musculo-skeletal modelling, 3D printing of bone models and also custom design of relevant prostheses starts from accurate STL files. These are obtained from medical imaging after careful segmentation and 3D reconstruction using specialized software, but most of these are very expensive. The aim of the present study is to assess and compare alternative software available for free. Three freeware software were selected from the most popular, and one standard platform was made available at the institute of the authors. Using each of these four software and starting from available DICOM files obtained previously by a CT scanner, three different bone models were reconstructed from each of five different human anatomical areas for a total of 60 bone model reconstructions. A young radiographer performed the bone reconstruction without specific technical training. 3D spatial matching of corresponding anatomical models was also performed to determine distance-maps for the assessment of final surface quality. In all four software many valuable features were available, with minimum differences, and bone models of good quality were obtained. Large differences in file sizes (mean range over the five anatomical models 66-338) and in the number of triangles (870-1350 thousands) were found, with triangles for MByte ratio ranging from about 4 to 20 thousands. The distance-map analysis revealed that root mean square deviation averaged over the five anatomical models ranged from 0.13 to 2.21 mm for the six spatial matches between the four software. These software are suitable for 3D bone model reconstruction, and do not require special training, and as such these can open up opportunities for biomechanical modelling and medical education.     

Identification of mechanosensitive genes in osteoblasts by comparative microarray studies using the rotating wall vessel and the random positioning machine

Weightlessness or microgravity of spaceflight induces bone loss due in part to decreased bone formation by unknown mechanisms. Due to difficulty in performing experiments in space, several ground-based simulators such as the Rotating Wall Vessel (RWV) and Random Positioning Machine (RPM) have become critical venues to continue studying space biology. However, these simulators have not been systematically compared to each other or to mechanical stimulating models. Here, we hypothesized that exposure to RWV inhibits differentiation and alters gene expression profiles of 2T3 cells, and a subset of these mechanosensitive genes behaves in a manner consistent to the RPM and opposite to the trends incurred by mechanical stimulation of mouse tibiae. Exposure of 2T3 preosteoblast cells to the RWV for 3 days inhibited alkaline phosphatase activity, a marker of differentiation, and downregulated 61 and upregulated 45 genes by more than twofold compared to static 1 g controls, as shown by microarray analysis. The microarray results were confirmed by real-time PCR and/or Western blots for seven separate genes and proteins including osteomodulin, runx2, and osteoglycin. Comparison of the RWV data to the RPM microarray study that we previously published showed 14 mechanosensitive genes that changed in the same direction. Further comparison of the RWV and RPM results to microarray data from mechanically loaded mouse tibiae reported by an independent group revealed that three genes including osteoglycin were upregulated by the loading and downregulated by our simulators. These mechanosensitive genes may provide novel insights into understanding the mechanisms regulating bone formation and potential targets for countermeasures against decreased bone formation during space flight and in pathologies associated with lack of bone formation.     

Congruence of individual cranial bone morphology and neutral molecular affinity patterns in modern humans

Recent studies have demonstrated that the shape of the human temporal bone is particularly strongly correlated with neutral genetic expectation, when compared against other cranial regions, such as the vault, face, and basicranium. In turn, this has led to suggestions that the temporal bone is particularly reliable in analyses of primate phylogeny and human population history. While several reasons have been suggested to explain the temporal bone's strong fit with neutral expectation, the temporal bone has never systematically been compared against other individual cranial bones defined using the same biological criteria. Therefore, it is currently unknown whether the shapes of all cranial bones possess reliable information regarding neutral genetic evolution, or whether the temporal bone is unique in this respect. This study tests the hypothesis that the human temporal bone is more congruent with neutral expectation than six other individual cranial bones by correlating population affinity matrices generated using neutral genetic and 3D craniometric data. The results demonstrate that while the temporal bone shows the absolute strongest correlation with neutral genetic data compared with all other bones, it is not statistically differentiated from the sphenoid, frontal, and parietal bones in this regard. Potential reasons for the temporal bone's consistently strong fit with neutral expectation, such as its overall anatomical complexity and/or its contribution to the architecture of the basicranium, are examined. The results suggest that future phylogenetic and taxonomic studies would benefit from considering the shape of the entire cranium minus those regions that deviate most from neutrality. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.