Serena Bonaretti

Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training.

SummaryIn this study, we determined that operator positioning precision contributes significant measurement error in high-resolution peripheral quantitative computed tomography (HR-pQCT). Moreover, we developed software to quantify intra- and inter-operator variability and demonstrated that standard positioning training (now available as a web-based application) can significantly reduce inter-operator variability.IntroductionHR-pQCT is increasingly used to assess bone quality, fracture risk, and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection (“scout view image”) and define the region to be scanned by positioning a “reference line” on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators.MethodsTo evaluate the operator in vivo measurement precision, we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner’s software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled six new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group.ResultsIn vivo precision errors were up to threefold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. The inter-operator precision errors were significantly greater than the short-term intra-operator precision (p < 0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators and lower inter-operator reproducibility (p < 0.001). Precision errors were significantly greater for the radius than for the tibia.ConclusionOperator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online (http://webapps.radiology.ucsf.edu/refline/).

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.

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.

Novel anthropomorphic hip phantom corrects systemic interscanner differences in proximal femoral vBMD.

Quantitative computed tomography (QCT) is increasingly used in osteoporosis studies to assess volumetric bone mineral density (vBMD), bone quality and strength. However, QCT is confronted by technical issues in the clinical research setting, such as potentially confounding effects of body size on vBMD measurements and lack of standard approaches to scanner cross-calibration, which affects measurements of vBMD in multicenter settings. In this study, we addressed systematic inter-scanner differences and subject-dependent body size errors using a novel anthropomorphic hip phantom, containing a calibration hip to estimate correction equations, and a contralateral test hip to assess the quality of the correction. We scanned this phantom on four different scanners and we applied phantom-derived corrections to in vivo images of 16 postmenopausal women scanned on two scanners. From the phantom study, we found that vBMD decreased with increasing phantom size in three of four scanners and that inter-scanner variations increased with increasing phantom size. In the in vivo study, we observed that inter-scanner corrections reduced systematic inter-scanner mean vBMD differences but that the inter-scanner precision error was still larger than expected from known intra-scanner precision measurements. In conclusion, inter-scanner corrections and body size influence should be considered when measuring vBMD from QCT images.

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.

Comparison of Different Approaches for Measuring Tibial Cartilage Thickness

Abstract 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.

Object removal in gradient domain of cone-beam CT projections

We propose a method to reduce streak artifacts in cone-beam CT reconstructions that arise from the edges of dense objects outside the 3D field-of-view. To this end, ramp filtering is decomposed into a derivative- and a Hilbert transform step. This allows for spectral inpainting directly in gradient domain, such that only contributions of sharp edges are removed. We applied our approach to weight-bearing knee imaging data, where plastic pipes outside the field-of-view introduce notable streak artifacts. Streak artifacts in the reconstructions are reduced and on semi-simulated data the correlation coefficient could be improved from 0.88 to 0.99. The method is applicable for arbitrary object shapes and can be easily integrated into existing FDK reconstruction algorithms.