Danmei Liu

Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR‐pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition‐realistic phantoms constructed from cadaveric radii. Single‐center precision was determined by repeat scanning over short‐term (<72 hours), intermediate‐term (3–5 months), and long‐term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR‐pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single‐center short‐term RMSCVs were <1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate‐term RMSCVs were generally not statistically different from short‐term values. Long‐term variability was significantly greater for all density measures (0.7% to 2.0%; p < 0.05 versus short‐term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p < 0.01 versus short‐term), cortical porosity (Ct.Po) (15.4%; p < 0.01 versus short‐term), and trabecular thickness (Tb.Th) (2.2%; p < 0.01 versus short‐term). Multicenter RMSCVs were also significantly higher than short‐term values: 2% to 4% for density and micro–finite element analysis (µFE) measures (p < 0.0001), 2.6% to 5.3% for morphometric measures (p < 0.001), whereas Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multicenter precision errors for HR‐pQCT parameters were generally less than 5%. Phantom‐based multicenter precision was comparable to previously reported in in vivo single‐center precision errors, although this was approximately two to five times worse than ex vivo short‐term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs.

Tibial geometry is associated with failure load ex vivo: a MRI, pQCT and DXA study

SummaryWe studied the relations between bone geometry and density and the mechanical properties of human cadaveric tibiae. Bone geometry, assessed by MRI and pQCT, and bone density, assessed by DXA, were significantly associated with bone’s mechanical properties. However, cortical density assessed by pQCT was not associated with mechanical properties.IntroductionThe primary objective of this study was to determine the contribution of cross-sectional geometry (by MRI and pQCT) and density (by pQCT and DXA) to mechanical properties of the human cadaveric tibia.MethodsWe assessed 20 human cadaveric tibiae. Bone cross-sectional geometry variables (total area, cortical area, and section modulus) were measured with MRI and pQCT. Cortical density and areal BMD were measured with pQCT and DXA, respectively. The specimens were tested to failure in a four-point bending apparatus. Coefficients of determination between imaging variables of interest and mechanical properties were determined.ResultsCross-sectional geometry measurements from MRI and pQCT were strongly correlated with bone mechanical properties (r2 range from 0.55 to 0.85). Bone cross-sectional geometry measured by MRI explained a proportion of variance in mechanical properties similar to that explained by pQCT bone cross-sectional geometry measurements and DXA measurements.ConclusionsWe found that there was a close association between geometry and mechanical properties regardless of the imaging modality (MRI or pQCT) used.

Physical activity positively predicts bone architecture and bone strength in adolescent males and females.

Aims:  Physical activity (PA) has positive effects on bone accrual and geometry in children during growth. However, we do not know how PA influences adaptations in bone architecture during growth. We evaluated the contribution of PA to bone density, architecture and strength in adolescents.

Assessing Bone Microstructure at the Distal Radius in Children and Adolescents Using HR-pQCT: A Methodological Pilot Study

We examined the use of high-resolution peripheral quantitative computed tomography (HR-pQCT [XtremeCT; Scanco Medical, Switzerland]) to assess bone microstructure at the distal radius in growing children and adolescents. We examined forearm radiographs from 37 children (age 8-14 yr) to locate the position of the ulnar and radial growth plates. We used HR-pQCT to assess bone microstructure in a region of interest (ROI) at the distal radius that excluded the growth plate (as determined from the radiographs) in all children (n=328; 9-21 yr old). From radiographs, we determined that a ROI in the distal radius at 7% of bone length excluded the radial growth plate in 100% of participants. We present bone microstructure data at the distal radius in children and adolescents. From the HR-pQCT scans, we observed active growth plates in 80 males (aged 9.5-20.7 yr) and 92 females (aged 9.5-20.2 yr). The ulnar plate was visible in 9 male and 17 female participants (aged 11.2 ± 1.9yr). The HR-pQCT scan required 3 min with a relatively low radiation dose (<3 μSv). Images from the radial ROI were free of artifacts and outlined cortical and trabecular bone microstructure. There is currently no standard method for these measures; therefore, these findings provide insight for investigators using HR-pQCT for studies of growing children.

Bone and Muscle Parameters of the Tibia: Agreement Between the XCT 2000 and XCT 3000 Instruments

Peripheral quantitative computed tomography is a valuable tool to assess bone in children across growth, with long-term studies capturing nuances missed in cross-sectional studies. As children grow, a change from XCT 2000 to a XCT 3000 may be required to accommodate the increasing size of the lower limbs. We examined the precision and agreement between the Stratec XCT 2000 and 3000 on selected bone and muscle parameters. Twenty-eight participants (mean+/-SD; age 27.5+/-6.5 yr) underwent scans at the distal (8%), mid (50%), and proximal (66%) tibia sites, to assess total bone area, total bone density, and trabecular density (8% site); and total bone area, cortical area, cortical density (CoD), polar strength-strain index, and muscle cross-sectional area (50% and 66% sites). Outcomes between instruments were highly correlated; r=0.90-0.99 for CoD across sites, with r=0.97-0.99 for all other measures. Bland and Altman plots showed excellent agreement between instruments for all variables. Regression indicated no significant relationship between instrument and size of measurement (p>0.05). Coefficients of variation were lower than previously reported (0.4-2.4%). For longitudinal studies, the XCT 3000 can replace the XCT 2000 with minimal influence on bone and muscle parameters.

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/).

Elasticity and Viscoelasticity of Human Tibial Cortical Bone Measured by Nanoindentation

Bone is a composite material composed of collagen, carbonated apatite mineral, water, and other non-collagenous proteins. The bone structure inside human body is under constant remodelling. The mechanical properties of bone and their dynamic changes during remodelling are crucial to the health and quality of life. In this study, the elastic and viscoelastic properties of a 73 year-old female cortical bone were investigated at the lamellar level. This was realized with a nanoindentation technique equipped with dynamic loading function. 325 indentations were made in individual Haversian systems and interstitial bone at both dry and wet condition, and under two different loading frequencies. The results showed no statistically significant differences in elastic modulus between Haversian systems and interstitial bone. There were no systematic changes in modulus at lamellar level from the periosteal to the endosteal site. The lamellar structure of both Haversian system and interstitial bone is viscoelastic with water playing a significant role to the properties. When dry bone is hydrated, elastic modulus decreases and loss tangent increases.