Open-source image analysis tool for the identification and quantification of cortical interruptions and bone erosions in high-resolution peripheral quantitative computed tomography images of patients with rheumatoid arthritis.

Identification of bone erosions and quantification of erosion volume is important for rheumatoid arthritis diagnosis, and can add important information to evaluate disease progression and treatment effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) is well suited for this purpose, however analysis methods are not widely available. The purpose of this study was to develop an open-source software tool for the identification and quantification of bone erosions using images acquired by HR-pQCT. The collection of modules, Bone Analysis Modules (BAM) - Erosion, implements previously published erosion analysis techniques as modules in 3D Slicer, an open-source image processing and visualization tool. BAM includes a module to automatically identify cortical interruptions, from which erosions are manually selected, and a hybrid module that combines morphological and level set operations to quantify the volume of bone erosions. HR-pQCT images of the second and third metacarpophalangeal (MCP) joints were acquired in patients with RA (XtremeCT, n = 14, XtremeCTII, n = 22). The number of cortical interruptions detected by BAM-Erosion agreed strongly with the previously published cortical interruption detection algorithm for both XtremeCT (r2 = 0.85) and XtremeCTII (r2 = 0.87). Erosion volume assessment by BAM-Erosion agreed strongly (r2 = 0.95) with the Medical Image Analysis Framework. BAM-Erosion provides an open-source erosion analysis tool that produces comparable results to previously published algorithms, with improved options for visualization. The strength of the tool is that it implements multiple image processing algorithms for erosion analysis on a single, widely available, open-source platform that can accommodate future updates.

Do femoral version abnormalities play a role in hip function of patients with hip pain?

BACKGROUND: A high prevalence of femoral version abnormalities has been observed in hip pain patients, with impact on hip range of motion and muscle strength that should be elucidated. METHODS: Cross-sectional study. Thirty-one patients with hip pain (16 men and 15 female) were subjected to Biplanar X-Rays to quantify femoral version using three-dimensional measurements. The 62 hips were divided into normal version (10-20°, n = 18), anteverted (>20°, n = 19), and retroverted (<10°, n = 25). Joint range of motion for flexion, internal rotation, and external rotation was assessed through digital goniometry. Maximal isometric hip strength (flexion, extension, internal rotation, external rotation at 0° and 30°, abduction, adduction) was evaluated through hand-held dynamometry. Hip rotation index was calculated as external rotation minus internal rotation. FINDINGS: Anteverted hips had greater internal rotation, while retroverted hips had greater external rotation (p = 0.001). Anteverted hips were weaker than retroverted hips for external rotation at 30° (p < 0.001), abduction (p = 0.006) and adduction (p < 0.001), and weaker than normal version hips for extension (p = 0.018). All three groups had different rotation index: retroverted>normal>anteverted (p < 0.001). The ordinal logistic regression found higher values of rotation index with higher probability of being retroverted (common odds ratio = 1.20). There was a strong correlation between femoral version group and rotation index (rS = 0.76, p < 0.001). There was probability >70% of a hip being anteverted if the rotation index was <11°, and being retroverted if the index was >40°. INTERPRETATION: Range of motion and muscle strength differed in hips with different femoral versions. The hip rotation index was a strong femoral version predictor.

Assessing the Sensitivity of Dual-Energy Computed Tomography 3-Material Decomposition for the Detection of Gout.

OBJECTIVES: The aim of this study was to assess the accuracy and precision of a novel application of 3-material decomposition (3MD) with virtual monochromatic images (VMIs) in the dual-energy computed tomography (DECT) assessment of monosodium urate (MSU) and hydroxyapatite (HA) phantoms compared with a commercial 2-material decomposition (2MD) and dual-thresholding (DT) material decomposition methods. MATERIALS AND METHODS: Monosodium urate (0.0, 3.4, 13.3, 28.3, and 65.2 mg/dL tubes) and HA (100, 400, and 800 mg/cm 3 tubes) phantoms were DECT scanned individually and together in the presence of the foot and ankle of 15 subjects. The raw data were decomposed with 3MD-VMI, 2MD, and DT to produce MSU-only and HA-only images. Mean values of 10 × 10 × 10-voxel volumes of interest (244 µm 3 ) placed in each MSU and HA phantom well were obtained and compared with their known concentrations and across measurements with subjects' extremities to obtain accuracy and precision measures. A statistical difference was considered significant if P < 0.05. RESULTS: Compared with known phantom standards, 3MD-VMI was accurate for the detection of MSU concentrations as low as 3.4 mg/dL ( P = 0.75). In comparison, 2MD was limited to 13.3 mg/dL ( P = 0.06) and DT was unable to detect MSU concentrations below 65.2 mg/L ( P = 0.16). For the HA phantom, 3MD-VMI and 2MD were accurate for all concentrations including the lowest at 100 mg/cm 3 ( P = 0.63 and P = 0.55, respectively). Dual-thresholding was not useful for the decomposition of HA phantom. Precision was high for both 3MD-VMI and 2MD measurements for both MSU and HA phantoms. Qualitatively, 3MD-VMI MSU-only images demonstrated reduced beam-hardening artifact and voxel misclassification, compared with 2MD and DT. CONCLUSIONS: Three-material decomposition-VMI DECT is accurate for quantification of MSU and HA concentrations in phantoms and accurately detects a lower concentration of MSU than either 2MD or DT. For concentration measurements of both MSU and HA phantoms, 3MD-VMI and 2MD have high precision, but DT had limitations. Clinical implementation of 3MD-VMI DECT promises to improve the performance of this imaging modality for diagnosis and treatment monitoring of gout.

The utility of multi-stack alignment and 3D longitudinal image registration to assess bone remodeling in rheumatoid arthritis patients from second generation HR-pQCT scans.

BACKGROUND: Medical imaging plays an important role in determining the progression of joint damage in rheumatoid arthritis (RA). High resolution peripheral quantitative computed tomography (HR-pQCT) is a sensitive tool capable of evaluating bone microarchitecture and erosions, and 3D rigid image registration can be used to visualize and quantify bone remodeling over time. However, patient motion during image acquisition can cause a "stack shift" artifact resulting in loss of information and reducing the number of erosions that can be analyzed using HR-pQCT. The purpose of this study was to use image registration to improve the number of useable HR-pQCT scans and to apply image-based bone remodeling assessment to the metacarpophalangeal (MCP) joints of RA patients. METHODS: Ten participants with RA completed HR-pQCT scans of the 2nd and 3rd MCP joints at enrolment to the study and at a 6-month follow-up interval. At 6-months, an additional repeat scan was acquired to evaluate reliability. HR-pQCT images were acquired in three individual 1 cm acquisitions (stacks) with a 25% overlap. We completed analysis first using standard evaluation methods, and second with multi-stack registration. We assessed whether additional erosions could be evaluated after multi-stack registration. Bone remodeling analysis was completed using registration and transformation of baseline and follow-up images. We calculated the bone formation and resorption volume fractions with 6-month follow-up, and same-day repositioning as a negative control. RESULTS: 13/57 (23%) of erosions could not be analyzed from raw images due to a stack shift artifact. All erosions could be volumetrically assessed after multi-stack registration. We observed that there was a median bone formation fraction of 2.1% and resorption fraction of 3.8% in RA patients over the course of 6 months. In contrast to the same-day rescan negative control, we observed median bone formation and resorption fractions of 0%. CONCLUSIONS: Multi-stack image registration is a useful tool to improve the number of useable scans when analyzing erosions using HR-pQCT. Further, image registration can be used to longitudinally assess bone remodeling. These methods could be implemented in future studies to provide important pathophysiological information on the progression of bone damage.

Interactive graph-cut segmentation for fast creation of finite element models from clinical ct data for hip fracture prediction.

In this study, we propose interactive graph cut image segmentation for fast creation of femur finite element (FE) models from clinical computed tomography scans for hip fracture prediction. Using a sample of N = 48 bone scans representing normal, osteopenic and osteoporotic subjects, the proximal femur was segmented using manual (gold standard) and graph cut segmentation. Segmentations were subsequently used to generate FE models to calculate overall stiffness and peak force in a sideways fall simulations. Results show that, comparable FE results can be obtained with the graph cut method, with a reduction from 20 to 2-5 min interaction time. Average differences between segmentation methods of 0.22 mm were not significantly correlated with differences in FE derived stiffness (R2 = 0.08, p = 0.05) and weakly correlated to differences in FE derived peak force (R2 = 0.16, p = 0.01). We further found that changes in automatically assigned boundary conditions as a consequence of small segmentation differences were significantly correlated with FE derived results. The proposed interactive graph cut segmentation software MITK-GEM is freely available online at https://simtk.org/home/mitk-gem .

Longitudinal HR-pQCT and image registration detects endocortical bone loss in kidney transplantation patients.

Patients with chronic kidney disease (CKD) who undergo kidney transplantation experience bone loss and increased risk of fracture. However, the mechanisms of this bone loss are unclear. Our objective was to use image registration to define the cortex to assess changes in cortical porosity (Ct.Po) in patients undergoing first-time kidney transplantation. We obtained serial measurements of parathyroid hormone (PTH) and bone turnover markers and used high-resolution peripheral quantitative computed tomography (HR-pQCT) to scan the distal radius and tibia in 31 patients (21 men, 10 women; aged 51.9 ± 13.4 years) at transplant and after 1 year. Baseline and 1-year images were aligned using a fully automated, intensity-based image registration framework. We compared three methods to define the cortical region of interest (ROI) and quantify the changes: 1) cortical bone was independently defined in baseline and follow-up scans; 2) cortical bone was defined as the common cortical ROI; and 3) the cortical ROI at baseline was carried forward to 1-year follow-up (baseline-indexed). By the independently defined ROI, Ct.Po increased 11.7% at the radius and 9.1% at the tibia, whereas by the common ROI, Ct.Po increased 14.6% at the radius and 9.1% at the tibia. By the baseline-indexed ROI, which provides insight into changes at the endocortical region, Ct.Po increased 63.4% at the radius and 17.6% at the tibia. We found significant relationships between changes in Ct.Po and bone formation and resorption markers at the radius. The strongest associations were found between markers and Ct.Po using the baseline-index method. We conclude that Ct.Po increases throughout the cortex after kidney transplant, and this increase is particularly marked at the endocortical surface. These methods may prove useful for all HR-pQCT longitudinal studies, particularly when changes are expected at the endocortical region.

Assessing the local mechanical environment in medial opening wedge high tibial osteotomy using finite element analysis.

High-tibial osteotomy (HTO) is a surgical technique aimed at shifting load away from one tibiofemoral compartment, in order the reduce pain and progression of osteoarthritis (OA). Various implants have been designed to stabilize the osteotomy and previous studies have been focused on determining primary stability (a global measure) that these designs provide. It has been shown that the local mechanical environment, characterized by bone strains and segment micromotion, is important in understanding healing and these data are not currently available. Finite element (FE) modeling was utilized to assess the local mechanical environment provided by three different fixation plate designs: short plate with spacer, long plate with spacer and long plate without spacer. Image-based FE models of the knee were constructed from healthy individuals (N = 5) with normal knee alignment. An HTO gap was virtually added without changing the knee alignment and HTO implants were inserted. Subsequently, the local mechanical environment, defined by bone compressive strain and wedge micromotion, was assessed. Furthermore, implant stresses were calculated. Values were computed under vertical compression in zero-degree knee extension with loads set at 1 and 2 times the subject-specific body weight (1 BW, 2 BW). All studied HTO implant designs provide an environment for successful healing at 1 BW and 2 BW loading. Implant von Mises stresses (99th percentile) were below 60 MPa in all experiments, below the material yield strength and significantly lower in long spacer plates. Volume fraction of high compressive strain ( > 3000 microstrain) was below 5% in all experiments and no significant difference between implants was detected. Maximum vertical micromotion between bone segments was below 200 µm in all experiments and significantly larger in the implant without a tooth. Differences between plate designs generally became apparent only at 2 BW loading. Results suggest that with compressive loading of 2 BW, long spacer plates experience the lowest implant stresses, and spacer plates (long or short) result in smaller wedge micromotion, potentially beneficial for healing. Values are sensitive to subject bone geometry, highlighting the need for subject-specific modeling. This study demonstrates the benefits of using image-based FE modeling and bone theory to fine-tune HTO implant design.

Embryonic stem cells incorporate into newly formed bone and do not form tumors in an immunocompetent mouse fracture model.

Embryonic stem (ES) cells are a uniquely self-renewing, pluripotent population of cells that must be differentiated before being useful for cell therapy. Since most studies utilize subcutaneous implantation to test the in vivo functionality of ES cell-derived cells, the objective of the current study was to develop an appropriate and clinically relevant in vivo implantation system in which the behavior and tumorigenicity of ES cell-derived cells could be effectively tested in a tissue-specific (orthotopic) site. Male ES cells were differentiated either into osteoblasts or chondrocytes using protocols that were previously developed and published by our laboratory. The differentiated cells were implanted into a burr-hole fracture created in the proximal tibiae of immunocompetent female mice, strain matched to the ES cell line. The ability of the differentiated ES cell-derived cells (bearing the Y chromosome) to incorporate into the newly formed bone was assessed by micro-computed tomography imaging and histochemistry. ES cells differentiated with either osteogenic or chondrogenic medium supplementation formed a soft tissue mass that disrupted the normal bone architecture by 4 weeks after implantation in some mice. In contrast, mice receiving osteoblastic cells that were differentiated in a three-dimensional type 1 collagen gel showed evidence of new bone formation at the defect site without evidence of tumor formation for up to 8 weeks after implantation. In this injury model, type 1 collagen is more effective than medium supplementation at driving more complete differentiation of ES cells, as evidenced by reducing their tumorigenicity. Overall, the current study emphasizes the importance of using an appropriate orthotopic implantation system to effectively test the behavior and tumorigenicity of the cells in vivo.

Quality control for bone quality parameters affected by subject motion in high-resolution peripheral quantitative computed tomography.

Subject motion during high-resolution peripheral quantitative computed tomography (HR-pQCT) causes image artifacts that affect morphological analysis of bone quality. The aim of our study was to determine effectiveness of techniques for quality control in the presence of motion in vivo including automated and manual approaches. First, repeatability of manual grading was determined within and between laboratories. Given proper training using a standardized scale and training images (provided by the manufacturer), we found that manual grading is suitable for repeatable image quality grading within and across sites (ICC>0.7). Both a new automated technique providing motion measures based on projection moments, and traditional manual grading (1=best, 5=worst) were subsequently used to assess subject data for motion in N=137 image pairs (scan/re-scan) from the Canadian Multicentre Osteoporosis Study (CaMos) Calgary cohort. High quality image pairs were selected and measurement precision was estimated by calculating the coefficient of variation (CV). Consistent with previous data, density parameters (e.g. total bone mineral density) are more robust than structural (e.g. trabecular number) or finite element parameters (e.g. failure load). To obtain acceptable measurement precision, images should not exceed a manual grading of 3 (on a scale from 1 to 5) or an automatic (ε(T)) grading of 1.2. Automatic and manual grading provide comparable quality control, but the advantage of the automated technique is its ability to provide a motion value at scan time (providing a basis for real time decision regarding re-scan requirements), and the assessment is objective. Notably, automatic motion measurement can be performed retrospectively based on original scan data, and is therefore well suited for multi-center studies as well as any research where objective quality control is paramount.

Automated quantification of three-dimensional subject motion to monitor image quality in high-resolution peripheral quantitative computed tomography.

Subject motion during acquisition of high-resolution peripheral quantitative computed tomography (HR-pQCT) results in image artifacts and interferes with quantification of bone architecture used to study bone-related diseases such as osteoporosis. We propose an automatic method to measure physical subject motion that frequently takes place during acquisition. Three measures derived from projection data are proposed to quantify motion artifacts: in-plane translation (ε(T)) and in-plane rotation (ε(R)) utilizing projection moments and longitudinal translation (ε(z)) based on tracking projection profiles. Validation was performed using a phantom containing sections of distal human cadaver radii attached to a mechanical device to precisely control in-plane rotation and longitudinal translation that was intentionally performed during HR-pQCT data acquisition. Motion measured by the new automated technique was compared to the known applied motion, and related to percent errors in morphological parameters quantifying bone properties. It was determined that of the three proposed measures, ε(T) best captured a quantified representation of image quality. ε(T) linearly relates to true physical in-plane translational motion (r(2) = 0.95, p<0.001) and is independent from longitudinal translational motion as well as the object being scanned. Additionally, ε(z) captures large longitudinal movements and combines well with ε(T) to fully characterize physical motion artifacts. The magnitude of ε(T) corresponds to morphological parameter error and is an excellent basis to select high-quality images. Morphological parameter errors from these experiments confirmed our earlier computer simulations which showed that increased subject motion resulted in artificially higher trabecular number, and artificially lower bone mineral density and cortical thickness. The magnitude and, notably, the uncertainty of the morphological errors increased with increased physical motion, and this impedes a direct linear compensation of parameter errors. The automated method presented provides a basis for consistent and objective quality assurance for HR-pQCT scanning, and addresses an important challenge for this novel imaging modality that is rapidly becoming an important basis for assessment and monitoring of bone quality.

European Society of Biomechanics S.M. Perren Award 2008: using temporal trends of 3D bone micro-architecture to predict bone quality.

In longitudinal studies, three-dimensional (3D) bone images are acquired at sequential time points essentially resulting in four-dimensional (4D) data for an individual. Based on the 4D data, we propose to calculate temporal trends and project these trends to estimate future bone architecture. Multiple consecutive deformation fields, calculated with Demons deformable image registration algorithm, were extrapolated on a voxel-by-voxel basis. Test data were from in vivo micro-computed tomography (microCT) scans of the proximal tibia of Wistar rats that were either ovariectomized (OVX; N=5) or sham operated (SHAM; N=6). Measurements performed at baseline, 4 and 8 weeks were the basis to predict the 12 week data. Predicted and actual 12 week data were compared using qualitative (3D rendering) and quantitative (geometry, morphology and micro-finite element, microFE) methods. The results indicated a voxel-based linear extrapolation scheme yielded mean geometric errors that were smaller than the voxel size of 15 microm. Key morphological parameters that were estimated included bone volume ratio (BV/TV; mean error 0.4%, maximum error 9%), trabecular thickness (Tb.Th; -1.1%, 11%), connectivity density (Conn.D; 9.0%, 18.5%) and the apparent Young's modulus (E(1); 6.0%, 32%). These data demonstrated a promising and novel approach for quantitatively capturing in vivo bone dynamics at the local trabecular level. The method does not require an a priori understanding of the diseases state, and can provide information about the trends of the bone remodeling process that may be used for better monitoring and treatment of diseases such as osteoporosis.

Improving geometric accuracy in the presence of susceptibility difference artifacts produced by metallic implants in magnetic resonance imaging.

Geometric and intensity distortions due to the presence of metallic implants in magnetic resonance imaging impede the full exploitation of this advanced imaging modality. The aim of this study is to provide a method for (a) quantifying and (b) reducing the implant distortions in patient images. Initially, a set of reference images (without distortion) was obtained by imaging a custom-designed three-dimensional grid phantom. Corresponding test images (containing the distortion) were acquired with the same imaging parameters, after positioning a specific metallic implant in the grid phantom. After determining: 1) the nonrecoverable; 2) the distorted, but recoverable; and 3) the unaffected areas, a point-based thin-plate spline image registration algorithm was employed to align the reference and test images. The calculated transformation functions utilized to align the image pairs described the implant distortions and could therefore be used to correct any other images containing the same distortions. The results demonstrate successful correction of grid phantom images with a metallic implant. Furthermore, the calculated correction was applied to porcine thigh images bearing the same metallic implant, simulating a patient environment. Qualitative and quantitative assessments of the proposed correction method are included.