High-resolution Peripheral Quantitative Computed Tomography Data Research Articles

Transferability of bone phenotyping and fracture risk assessment by μFRAC from first-generation high-resolution peripheral quantitative computed tomography to second-generation scan data.

The continued development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has led to a second-generation scanner with higher resolution and longer scan region. However, large multi-center prospective cohorts were collected with first-generation HR-pQCT and have been used to develop bone phenotyping and fracture risk prediction (μFRAC) models. This study establishes whether there is sufficient universality of these first-generation trained models for use with second-generation scan data. HR-pQCT data was collected for a cohort of 60 individuals, who had been scanned on both first- and second-generation scanners on the same day to establish the universality of the HR-pQCT models. These data were each used as input to first-generation trained bone microarchitecture models for bone phenotyping and fracture risk prediction, and their outputs were compared for each study participant. Reproducibility of the models were assessed using same-day repeat scans obtained from first-generation (n = 37) and second-generation (n = 74) scanners. Across scanner generations, the bone phenotyping model performed with an accuracy of 93.1%. Similarly, the five-year fracture risk assessment by μFRAC was well correlated with a Pearson's (r) correlation coefficient of r > 0.83 for the three variations of μFRAC (varying inclusion of clinical risk factors, finite element analysis, and dual X-ray absorptiometry). The first-generation reproducibility cohort performed with an accuracy for categorical assignment of 100% (bone phenotyping), and a correlation coefficient of 0.99 (μFRAC), the second-generation reproducibility cohort performed with an accuracy of 96.4% (bone phenotyping), and a correlation coefficient of 0.99 (μFRAC). We demonstrated that bone microarchitecture models trained using first-generation scan data generalize well to second-generation scans, performing with a high level of accuracy and reproducibility. Less than 4% of individuals' estimated fracture risk led to a change in treatment threshold, and in general these dissimilar outcomes using second-generation data tended to be more conservative.

Am I big boned? Bone length scaled reference data for HRpQCT measures of the radial and tibial diaphysis in White adults

Cross-sectional size of a long bone shaft influences its mechanical properties. We recently used high-resolution peripheral quantitative computed tomography (HRpQCT) to create reference data for size measures of the radial and tibial diaphyses. However, data did not take into account the impact of bone length. Human bone exhibits relatively isometric allometry whereby cross-sectional area increases proportionally with bone length. The consequence is that taller than average individuals will generally have larger z-scores for bone size outcomes when length is not considered. The goal of the current work was to develop a means of determining whether an individual's cross-sectional bone size is suitable for their bone length. HRpQCT scans performed at 30 % of bone length proximal from the distal end of the radius and tibia were acquired from 1034 White females (age = 18.0 to 85.3 y) and 392 White males (age = 18.4 to 83.6 y). Positive relationships were confirmed between bone length and cross-sectional areas and estimated mechanical properties. Scaling factors were calculated and used to scale HRpQCT outcomes to bone length. Centile curves were generated for both raw and bone length scaled HRpQCT data using the LMS approach. Excel-based calculators are provided to facilitate calculation of z-scores for both raw and bone length scaled HRpQCT outcomes. The raw z-scores indicate the magnitude that an individual's HRpQCT outcomes differ relative to expected sex- and age-specific values, with the scaled z-scores also considering bone length. The latter enables it to be determined whether an individual or population of interest has normal sized bones for their length, which may have implications for injury risk. In addition to providing a means of expressing HRpQCT bone size outcomes relative to bone length, the current study also provides centile curves for outcomes previously without reference data, including tissue mineral density and moments of inertia.

Evaluation of Bone Health Using High Resolution Peripheral Quantitative Computed Tomography in Survivors of Paediatric Acute Lymphoblastic Leukemia

Bone mass accrual, bone architecture, and strength may be impaired in children with a history of acute lymphoblastic leukemia (ALL) resulting in low bone mineral density (BMD) and fractures. The Children's Oncology Group recommends evaluating ALL survivors' bone health with dual-energy X-ray absorptiometry (DXA) testing. However, DXA testing may not accurately measure bone health in survivors due to low bone area for height, short stature, growth delays or decreased lean muscle mass. Further, it does not differentiate between trabecular and cortical bone, nor does it provide insights into bone microarchitecture and strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional non-invasive imaging modality that provides a comprehensive assessment bone microarchitecture, volumetric BMD (vBMD) of both cortical and trabecular bone, and bone strength. In adult patients, HR-pQCT parameters have been shown to predict incident fractures. In this pilot study we utilized HR-pQCT to evaluate bone microarchitecture, vBMD, bone geometry and bone strength of peri-pubertal and pubertal survivors of ALL compared to healthy controls. Methods: We prospectively recruited ALL survivors (>1 year off therapy) with a DXA BMD Z-score between -2.0 to 0 within the proceeding six months, who were in early-late puberty (pre-pubertal patients excluded), and aged 11 to 18 years, along with healthy controls in the same age range at a single academic pediatric center in Canada. While a BMD Z-score of -2.0 to 0 has historically been considered normal, many children with Z-scores in this range have skeletal fragility and an increased fracture risk. Patients were excluded if they had comorbidity that impacts bone microarchitecture (ex. chronic kidney disease), were on a medication that impacts bone health (ex. corticosteroids) or had a genetic syndrome that increased their sensitivity to radiation (ex. Ataxia Telangiectasia). HR-pQCT of the distal radius and tibia was performed using the a standardized protocol. Bone mass was compared using total, trabecular and cortical vBMD, bone architecture was compared using cortical porosity and bone strength was compared using failure load. HR-pQCT derived variables were compared between ALL and control groups following stratification by sex. HR-pQCT values were summarized using medians and interquartile ranges and medians were compared using the Wilcoxon signed-rank test. Demographic and clinical characteristics were compared using the chi-square test. All tests were two tailed and p<0.05 was considered significant. Results: A total of 59 subjects were recruited (34 ALL survivors, 25 healthy controls). The sex of participants was male for 56.0% (n=14) of controls and 61.7% (n=21) of ALL survivors and female for 44.0% (n=11) of controls and 38.3% (n=13) of survivors. All survivors had received corticosteroids and methotrexate, and five (15%) had received cranial radiation. ALL survivors were not more likely than controls to report a history of a fracture (32.4%, n=11 vs. 16%, n=4). Additional data regarding the participants demographics is presented in Table 1. Male survivors had a lower radial trabecular vBMD, tibial total vBMD, and tibial trabecular vBMD, and a higher tibial failure load compared to healthy male controls. Female survivors had a lower radial total vBMD, radial trabecular vBMD, tibial total vBMD, and tibial trabecular vBMD. Female ALL survivors also had higher radial and tibial failure loads compared to healthy female controls. No differences in cortical porosity or cortical vBMD were identified between survivors and healthy controls. Complete HR-pQCT data is presented in Table 2. Conclusions: We demonstrated differences in the HR-pQCT parameters of peripubertal and pubertal ALL survivors compared to healthy controls. Survivors had reductions in key HR-pQCT parameters and an increased tibial failure load compared to healthy controls. In future studies HR-pQCT should be performed at a uniform time point post ALL therapy and used to predict future adverse bone health outcome such as fractures. Using this HR-pQCT guided approach ALL survivors at greatest risk of an adverse bone health outcome can be offered early interventions to prevent these outcomes.

Utility of HR-pQCT in detecting training-induced changes in healthy adult bone morphology and microstructure.

Healthy bone adjusts its traits in an exceptionally coordinated, compensatory process. Recent advancements in skeletal imaging via High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) allows for the in vivo 3-dimensional and longitudinal quantification of bone density, microarchitecture, geometry, and parameters of mechanical strength in response to varying strain stimuli including those resulting from exercise or military training. Further, the voxel size of 61 microns has the potential to capture subtle changes in human bone in as little as 8 weeks. Given the typical time course of bone remodeling, short-term detection of skeletal changes in bone microstructure and morphology is indicative of adaptive bone formation, the deposition of new bone formation, uncoupled from prior resorption, that can occur at mechanistically advantageous regions. This review aims to synthesize existing training-induced HR-pQCT data in three distinct populations of healthy adults excluding disease states, pharmacological intervention and nutritional supplementation. Those included are: 1) military basic or officer training 2) general population and 3) non-osteoporotic aging. This review aims to further identify similarities and contrasts with prior modalities and cumulatively interpret results within the scope of bone functional adaptation.

OR13-01 Type 1 Diabetes Is Associated With Differential Skeletal Effects At The Onset Of Peak Bone Accrual

Abstract Disclosure: A.V. Brossfield: None. K.M. Williams: None. A.B. Sopher: None. D.J. McMahon: None. J. Fernando: None. S. Agarwal: None. M.R. Rubin: None. Objective: Type 1 diabetes (T1D) often develops prior to attainment of peak bone mass, yet few data exist regarding bone accretion in the peri-pubertal period. We hypothesized that T1D have disrupted bone architecture at the onset of peak bone mass accrual in association with hyperglycemia and advanced glycation endproduct (AGE) accumulation. Methods: We enrolled T1D and controls at onset of peak bone accretion (Tanner: girls 2/3, boys 3/4) and assessed aBMD by DXA and volumetric BMD (vBMD), microarchitecture, and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT) with finite element analysis (µFE) at the distal (4%) and proximal (30%) radius and tibia. We assessed time in hyperglycemia (>180 mg/dL) by continuous glucose monitoring and AGE accumulation by skin autofluorescence (SAF). Results: T1D (n=29, age 12.5 ± 0.3 [SE] yr, 79% male, 68% white) vs controls (n=31, 12.2 ± 0.3 yr, 55% male, 68% white) had higher BMI (21.3 ± 1 vs 18.4 ± 0.5 kg/m2; p=0.04), fasting glucose (168.5 ± 9 vs 88.4 ± 2 mg/dL; p<0.0001) and HbA1c (8.4 ± 0.8 vs 5.0 ± 0.2%; p=0.05) with a trend toward higher bone age (13.5 ± 0.3 vs 12.6 ± 0.3 yr, p=0.07) and lower 25OHD (24.0 ± 1 vs 34.8 ± 3 ng/mL, p=0.08). After multivariate adjustment (sex, bone age, height and weight), DXA showed decreased bone area in T1D at the total, sub-total, leg, rib and ultradistal radius, and decreased bone mineral content at the rib, leg and trochanter (ranging from -4.1% to -13.5%, all p <0.05). Multivariate adjusted HRpQCT data showed decreased trabecular area in T1D at the distal radius (169.9 ± 8 vs 201.2 ± 8 mm2; p=0.007) and tibia (578 ± 17 vs 631 ± 17 mm2; p=0.04) and decreased cortical perimeter at the distal radius (56.0 ± 1 vs 60.1 ± 1 mm2; p=0.009). However, T1D had increased cortical vBMD at the distal (698.2 ± 8 vs 663.5 ± 8 mg HA/cm3; p=0.004) and proximal radius (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and tibia (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and increased cortical thickness at the distal radius (0.74 ± 0.03 vs 0.64 ± 0.03 mm; p=0.03). There was no difference in bone strength by µFE. Within T1D, lower trabecular area at the distal radius was associated with higher SAF (β -69.26 ± 30 mm2; p=0.04) while higher cortical vBMD at the distal tibia was associated with higher time in hyperglycemia (β 0.633 ± 0.3 mg HA/cm3; p=0.03). Conclusion: T1D at the onset of peak bone accrual have decreased bone area and mineral content by DXA. They also have decreased trabecular area but increased cortical vBMD by HRpQCT, in association with AGE accumulation and hyperglycemia. We speculate that reduced bone turnover with hyperglycemia might lead to reduced area at more metabolically active trabecular sites but is compensated for by excess mineral accumulation at less active cortical sites, with overall maintenance of bone strength. Follow up will elucidate progression of these alterations during the growth spurt. Presentation: Friday, June 16, 2023

Using 3D image registration to maximize the reproducibility of longitudinal bone strength assessment by HR-pQCT and finite element analysis

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D rigid-body registration (3DR) to maximize reproducibility by accounting for misalignment between images. In our proposed approach, we used the full common bone volume defined by 3DR to estimate standard FE parameters. Using standard HR-pQCT imaging protocols, we validated the 3DR approach with ex vivo samples of the distal radius (n = 10, four repeat scans) by assessing whether 3DR can reduce measurement variability from repositioning error. We used in vivo data (n = 40, five longitudinal scans) to assess the sensitivity of 3DR to detect changes in bone strength at the distal radius by the standard deviation of the rate of change (σ), where the ideal value of σ is minimized to define true change. FE estimates by 3DR were compared to estimates by no registration (NR) and slice-matching (SM). Group-wise comparisons of ex vivo variation (CVRMS, %) found that FE measurement precision was improved by SM (CVRMS < 0.80%) and 3DR (CVRMS < 0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Longitudinal in vivo reproducibility was minimized by 3DR for failure load estimates (σ = 0.008 kN/month). Although 3D registration cannot negate motion artifacts, it plays an important role in detecting and reducing variability in FE estimates for longitudinal HR-pQCT data and is well suited for estimating effects of interventions in in vivo longitudinal studies of bone strength.

Soft tissue variations influence HR-pQCT density measurements in a spatially dependent manner.

Significant weight loss following treatments for obesity undermines bone metabolism and increases bone turnover and fracture incidence. High resolution peripheral quantitative computed tomography (HR-pQCT) is widely used in skeletal heath assessment research to provide noninvasive bone parameter measurement (e.g. volumetric bone mineral density (vBMD)) with minimal radiation exposure. However, variation in body composition among study groups or longitudinal variations within individuals undergoing significant weight change will generate artifacts and errors in HR-pQCT data. The purpose of this study is to determine the influence of these artifacts on the measurement of vBMD. We designed a custom-made hydroxyapatite (HA)-polymer phantom surrounded by layers of reusable gel pack and hydrogenated fat to mimic the distal tibia and the surrounding lean and fat tissue. Four different thicknesses of fat were used to mimic the soft tissue of increasingly overweight individuals. We then evaluated how a change in soft tissue thickness influenced image quality and vBMD quantification within total, trabecular, and cortical bone compartments. Based on these data, we applied a data correction to previously acquired clinical data in a cohort of gastric bypass patients. In the phantom measurements, total, trabecular, and cortical vBMD increased as soft tissue thickness decreased. The impact of soft tissue thickness on vBMD varied by anatomic quadrant. When applying the soft tissue data correction to a set of clinical data, we found that soft tissue reduction following bariatric surgery can lead to a clinically significant underestimation of bone loss in longitudinal data, and that the effect is most severe in the cortical compartment. HR-pQCT-based vBMD measurement accuracy is influenced by soft tissue thickness and is spatially inhomogeneous. Our results suggest that variations in soft tissue thickness must be considered in HR-pQCT studies, particularly in studies enrolling cohorts with differing body composition or in studies of longitudinal weight change.

Three-Dimensional Surface-Based Analysis of Cartilage MRI Data in Knee Osteoarthritis: Validation and Initial Clinical Application.

Traditional quantitative analysis of cartilage with MRI averages measurements (eg, thickness) across regions-of-interest (ROIs) which may reduce responsiveness. To validate and describe clinical application of a semiautomated surface-based method for analyzing cartilage relaxation times ("composition") and morphology on MRI, 3D cartilage surface mapping (3D-CaSM). Validation study in cadaveric knees and prospective observational (cohort) study in human participants. Four cadaveric knees and 14 participants aged 40-60 with mild-moderate knee osteoarthritis (OA) and 6 age-matched healthy volunteers, imaged at baseline, 1, and 6 months. 3D spoiled gradient echo, T1 rho/T2 magnetization-prepared 3D fast spin echo for mapping of T1 rho/T2 relaxation times and delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using variable flip angle T1 relaxation time mapping at 3T. 3D-CaSM was validated against high-resolution peripheral quantitative computed tomography (HRpQCT) in cadaveric knees, with comparison to expert manual segmentation. The clinical study assessed test-retest repeatability and sensitivity to change over 6 months for cartilage thickness and relaxation times. Bland-Altman analysis was performed for the validation study and evaluation of test-retest repeatability. Six-month changes were assessed via calculation of the percentage of each cartilage surface affected by areas of significant change (%SC), defined using thresholds based on area and smallest detectable difference (SDD). Bias and precision (0.06 ± 0.25 mm) of 3D-CaSM against reference HRpQCT data were comparable to expert manual segmentation (-0.13 ± 0.26 mm). 3D-CaSM demonstrated significant (>SDD) 6-month changes in cartilage thickness and relaxation times in both OA participants and healthy controls. The parameter demonstrating the greatest 6-month change was T2 relaxation time (OA median %SC [IQR] = 8.8% [5.5 to 12.6]). This study demonstrates the construct validity and potential clinical utility of 3D-CaSM, which may offer advantages to conventional ROI-based methods. 2. 2. J. Magn. Reson. Imaging 2020;52:1139-1151.

Identification, localization and differentiation of erosions and physiological bone channels by ultrasound in rheumatoid arthritis patients.

Ultrasound (US) can detect cortical bone lesions in RA. However, not all cortical bone lesions are erosions. Herein, we aimed to define whether US can differentiate between physiological bone channels and pathological erosions in RA and to provide topographic description of their differential localization. RA patients and healthy controls (HC) received US examination of the metacarpophalangeal (MCPJ) and proximal inter-phalangeal (PIPJ) joints adjudicating cortical bone lesions as physiological bone channels or pathological erosions. In a subset of RA patients and HC, high-resolution peripheral quantitative computed tomography (HR-pQCT) of the hand was performed to validate the classification of lesions. A total of 40 RA patients and 43 HC were enrolled and totally 771 MCPJ and 638 PIPJ were examined by US, and 94 and 51, respectively, by HR-pQCT. US-defined cortical bone lesions clustered in the lateral part of the MCP (50%) and the dorsal part of the PIPJ (66.7%) in RA. US-defined physiological bone channels clustered in the palmar parts of the MCPJ and PIPJ in both RA (78.8% and 100%, respectively) and HC (51.8% and 80%, respectively). HR-pQCT data confirmed US data with respect to adjudication of physiological bone channels and pathological erosions. Erosions were significantly (all P<0.000001) larger than physiological channels and preferentially localized at radial and ulnar sites, while physiological channels were clustered at palmar sites. Specificity of US was excellent for erosions in RA and for physiological bone channels in HC and RA. US allows differentiation between physiological channels and bone erosions in RA.

Review of high-resolution peripheral quantitative computed tomography for the assessment of bone microstructure and strength

Trabecular microstructure is an important factor in determining bone strength and physiological function. Normal X-ray and computed tomography (CT) cannot accurately reflect the microstructure of trabecular bone. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new imaging technique in recent years. It can qualitatively and quantitatively measure the three-dimensional microstructure and volume bone mineral density of trabecular bone in vivo. It has high precision and relative low dose of radiation. This new imaging tool is helpful for us to understand the trabecular microstructure more deeply. The finite element analysis of HR-pQCT data can be used to predict the bone strength accurately. We can assess the risk of osteoporosis and fracture with three-dimensional reconstructed images and trabecular microstructure parameters. In this review, we summarize the technical flow, data parameters and clinical application of HR-pQCT in order to provide some reference for the popularization and extensive application of HR-pQCT.

Changes in cortical microarchitecture are independent of areal bone mineral density in patients with fragility fractures

Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) are commonly used to assess the areal bone mineral density (aBMD) and peripheral microstructure, respectively. While DXA is the standard to diagnose osteoporosis, HR-pQCT provides information about the cortical and trabecular architecture. Many fragility fractures occur in patients who do not meet the osteoporosis criterion (i.e., T-score≤−2.5). We hypothesize that patients with T-score above −2.5 and fragility fracture may have abnormal bone microarchitecture. Therefore, in this retrospective clinical study, HR-pQCT data obtained from patients with fragility fractures and T-scores≥−2.5 (n=71) were compared to corresponding data from patients with fragility fractures and T-scores≤−3.5 (n=56). Types of secondary osteoporosis were excluded from the study. To verify the dependency of alterations in bone microarchitecture and T-score, the association between HR-pQCT values and aBMD as reflected by the T-score at both proximal femora, was assessed. At the distal tibia, cortical thickness was lower (p<0.001), cortical porosity was similar (p=0.61), trabecular number was higher (p<0.001), and bone volume fraction (BV/TV) was higher (p<0.001) in patients with T-scores≥−2.5 than in patients with T-scores≤−3.5. Trabecular number and BV/TV correlated with T-score (r=0.68, p<0.001; r=0.61, p<0.001), whereas the cortical values did not. Our results thus demonstrate the importance of bone structure, as assessed by HR-pQCT, in addition to the standard DXA T-score in the diagnosis of osteoporosis.

Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis.

Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research.

Bone Microarchitecture and Estimated Strength in 499 Adult Danish Women and Men: A Cross-Sectional, Population-Based High-Resolution Peripheral Quantitative Computed Tomographic Study on Peak Bone Structure

High-resolution peripheral quantitative computed tomography (HR-pQCT) allows in vivo assessment of cortical and trabecular bone mineral density (BMD), geometry, and microarchitecture at the distal radius and tibia in unprecedented detail. In this cross-sectional study, we provide normative and descriptive HR-pQCT data from a large population-based sample of Danish Caucasian women and men (n = 499) aged 20-80 years. In young adults (<35 years), women (n = 100) compared to men (n = 64) had smaller total and cortical areas, inferior metric trabecular indices, higher network inhomogeneity, lower cortical porosity, and lower finite element estimated bone strength. The changes in parameters with age were estimated from multiple regression analyses. In men, with age the greatest changes (from parameter minimum or maximum) until 80 years were found for cortical porosity (1.91 IQR), BV/TV (-1.09 IQR), and trabecular thickness (-0.87 IQR) in the radius and BV/TV (-1.55 IQR), cortical BMD (-1.25 IQR), and cortical porosity (1.25 IQR) in the tibia. In women changes were most pronounced for cortical porosity (4.76 IQR), trabecular inhomogeneity (3.84 IQR), and cortical BMD (-2.86 IQR) in the radius and cortical BMD (-5.06 IQR), cortical porosity (3.86 IQR), and cortical area (-1.64 IQR) in the tibia. These findings emphasize the age- and sex-related differences in bone morphology, with men having a structural advantage over women from early adult life translating into superior indices of bone strength. With age women are further disadvantaged compared to men by greater decrements in cortical and trabecular architecture in the radius and cortical architecture in the tibia.

SAT0095 Periarticular Bone Loss in Female Patients with Rheumatoid Arthritis: A Case-Control Study Using HR-PQCT

BackgroundPeriarticular bone loss is an early sign of bone involvement in rheumatoid arthritis (RA) and a predictor of subsequent radiographic erosion. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a non-invasive...

The effect of voxel size on high‐resolution peripheral computed tomography measurements of trabecular and cortical bone microstructure

Accurate quantification of bone microstructure plays a significant role in understanding bone mechanics and response to disease or treatment. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows for the quantification of trabecular and cortical structure in vivo, with the capability of generating images at multiple voxel sizes (41, 82, and 123 μm). The aim of this study was to characterize the effect of voxel size on structural measures of trabecular and cortical bone and to determine accuracy in reference to micro-CT ([micro sign]CT), the gold standard for bone microstructure quantification. Seventeen radii from human cadaver specimens were imaged at each HR-pQCT voxel size and subsequently imaged using [micro sign]CT. Bone density and microstructural assessment was performed in both the trabecular and cortical compartments, including cortical porosity quantification. Two distinct analysis techniques were applied to the 41 μm HR-pQCT data: the standard clinical indirect analysis and a direct analysis requiring no density or structural model assumptions. Analysis parameters were adjusted to enable segmentation and structure extraction at each voxel size. For trabecular microstructural measures, the 41 μm HR-pQCT data displayed the strongest correlations and smallest errors compared to [micro sign]CT data. The direct analysis technique applied to the 41 μm data yielded an additional improvement in accuracy, especially for measures of trabecular thickness. The 123 μm data performed poorly, with all microstructural measures either having moderate or nonsignificant correlations with [micro sign]CT data. Trabecular densitometric measures showed strong correlations to [micro sign]CT data across all voxel sizes. Cortical thickness was strongly correlated with [micro sign]CT values across all HR-pQCT voxel sizes. The accuracy of cortical porosity parameters was highly dependent on voxel size; again, the 41 μm data was most strongly correlated. Measures of cortical density and pore diameter at all HR-pQCT voxel sizes had either weak or nonsignificant correlations. This study demonstrates the effect of voxel size on the accuracy of HR-pQCT measurements of trabecular and cortical microstructure and presents parameters for HR-pQCT analysis at nonstandard resolutions. For all parameters measured, correlations were strongest at 41 μm. Weak correlations for porosity measures indicate that a better understanding of pore structure and resolution dependence is needed.

Volumetric bone mineral density at the spine and hip in Chinese American and White women

This study evaluated racial differences in bone size and volumetric density at the spine and hip in pre- and postmenopausal Chinese American and White women. Compared with White women, Chinese American women have greater cortical volumetric bone density (vBMD) at the hip, congruent with the results at the peripheral skeleton. Chinese American women have lower rates of fracture than White women despite lower areal bone density. At the forearm and tibia, however, Chinese American women have higher cortical vBMD as well as greater trabecular and cortical thickness, but smaller bone area as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) compared with White women. Since HR-pQCT data are obtained at peripheral sites, it is unclear whether these differences are relevant to the clinically important lumbar spine and hip. This study assesses racial differences in bone size and vBMD at the spine and hip in Chinese American and White women. QCT of the spine and hip was measured to assess racial differences in bone size, structure, and vBMD in pre- (n = 83) and postmenopausal (n = 50) Chinese American and White women. Data were adjusted for weight, height, physical activity, total calcium intake, parathyroid hormone, and 25-hydroxyvitamin D levels. Among premenopausal women, lumbar spine trabecular vBMD was 5.8% greater in Chinese American versus White women (p = 0.01). At the hip, cortical vBMD was 3% greater at the femoral neck (p = 0.05) and 3.6% greater at the total hip (p = 0.01) in premenopausal Chinese American compared with White women. Among postmenopausal women, there was no difference in lumbar spine trabecular vBMD. Cortical vBMD was 4% greater at the total hip (p = 0.02) and tended to be greater at the femoral neck (p = 0.058) in Chinese American versus White women. Consistent with earlier findings in the peripheral skeleton, cortical vBMD is greater at the hip in Chinese American versus White women.

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 (εT) and in-plane rotation (εR) utilizing projection moments and longitudinal translation (εz) 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, εT best captured a quantified representation of image quality. εT linearly relates to true physical in-plane translational motion (r2 = 0.95, p<0.001) and is independent from longitudinal translational motion as well as the object being scanned. Additionally, εz captures large longitudinal movements and combines well with εT to fully characterize physical motion artifacts. The magnitude of εT 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.

Variations in morphological and biomechanical indices at the distal radius in subjects with identical BMD

Determination of osteoporotic status is based primarily on areal bone mineral density (aBMD) obtained through dual X-ray absorptiometry (DXA). However, many fractures occur in patients with T-scores above the WHO threshold of osteoporosis, in part because DXA measures are insensitive to biomechanically important alterations in bone quality. The goal of this study was to determine – within groups of subjects with identical radius aBMD values – the extant variation in densitometric, geometric, microstructural, and biomechanical parameters. High resolution peripheral quantitative computed tomography (HR-pQCT) and DXA radius data from males and females spanning large ranges in age, osteoporotic status, and anthropometrics were compiled. 262 distal radius datasets were processed for this study. HR-pQCT scans were analyzed according to the manufacturer’s standard clinical protocol to quantify densitometric, geometric, and microstructural indices. Micro-finite element analysis was performed to calculate biomechanical indices. Factor of risk of wrist fracture was calculated. Simulated aBMD calculated from HR-pQCT data was used to group scans for evaluation of variation in quantified indices. Indices reflecting the greatest variation within aBMD level were BMD in the central portion of the trabecular compartment (max CV 142), trabecular heterogeneity (max CV 90), and intra-cortical porosity (max CV 151). Of the biomechanical indices, cortical load fraction had the greatest variation (max CV 38). Substantial variations in indices reflecting density, structure, and biomechanical competence exist among subjects with identical aBMD levels. Overlap of these indices among osteoporotic status groups reflects the reported incidence of osteoporotic fracture in subjects classified as osteopenic or normal.

Fast and Accurate 3-D Registration of HR-pQCT Images

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new noninvasive bone imaging technology that generates high-resolution 3-D images for quantitatively analysis of the bone microarchitecture in human. To enable quantitative evaluation of bone changes, either bone gain or loss, accurate alignment between the baseline and follow-up scans of the same individual is necessary. The major difficulties in achieving efficient and automatic registration of the HR-pQCT data are the large data size, deformations in the nonskeletal structures, and the complexity of the trabecular bone geometry. In this paper, we propose an automatic surface-based approach for fast and accurate registration of the HR-pQCT data, where the rigid registration is applied on the surfaces of the bony structures extracted from the grayscale HR-pQCT. The bony structure segmentation is performed via an automatic method that can adaptively determine the thresholds for separating the bony structure from the background and nonskeletal tissues. Experimental results performed on ten pairs of baseline and follow-up wrist scans of five adolescents and five elderly patients with osteoporosis showed the advantage of the proposed method in the high degree of automation, while the resultant parameters describing bone mineral density and trabecular architecture after registration were comparable with the outputs of the scanner's software. This automatic and accurate matching procedure may contribute to the clinical application and research of HR-pQCT.