Reliability of Annual Changes and Monitoring Time Intervals for Bone Strength, Size, Density, and Microarchitectural Development at the Distal Radius and Tibia in Children: A 1-Year HR-pQCT Follow-Up
Abstract:High‐resolution peripheral quantitative computed tomography (HR‐pQCT) imaging, together with computational finite element analysis (FEA), offers an attractive, noninvasive tool to quantify bone strength development in pediatric studies. Evidence of annual changes and errors in repeated HR‐pQCT measures is limited, and time intervals required to reliably capture changes in children's bone strength or microarchitecture have not yet been defined. Our objectives were: (1) to quantify annual changes in bone strengt… Show more
“…Further, as per recommendations by the International Society for Clinical Densitometry (ISCD), we computed the least significant change (LSC). (24)(25)(26)…”
Repositioning error in longitudinal high-resolution peripheral-quantitative computed tomography (HR-pQCT) imaging can lead to different bone volumes being assessed over time. To identify the same bone volumes at each time point, image registration is used. While crosssectional area image registration corrects axial misalignment, 3D registration additionally corrects rotations. Other registration methods involving matched angle analysis (MA) or boundary transformations (3D-TB) can be used to limit interpolation error in 3D-registering micro-finite-element data. We investigated the effect of different image registration methods on short-term in vivo precision in adults with osteogenesis imperfecta, a collagen-related genetic disorder resulting in low bone mass, impaired quality, and increased fragility. The radii and tibiae of 29 participants were imaged twice on the same day with full repositioning. We compared the precision error of different image registration methods for density, microstructural, and micro-finite-element outcomes with data stratified based on anatomical site, motion status, and scanner generation. Regardless of the stratification, we found that image registration improved precision for total and trabecular bone mineral densities, trabecular and cortical bone mineral contents, area measurements, trabecular bone volume fraction, separation, and heterogeneity, as well as cortical thickness and perimeter. 3D registration marginally outperformed cross-sectional area registration for some outcomes, such as trabecular bone volume fraction and separation. Similarly, precision of micro-finite-element outcomes was improved after image registration, with 3D-TB and MA methods providing greatest improvements. Our regression model confirmed the beneficial effect of image registration on HR-pQCT precision errors, whereas motion had a detrimental effect on precision even after image registration. Collectively, our results indicate that 3D registration is recommended for longitudinal HR-pQCT imaging in adults with osteogenesis imperfecta. Since our precision errors are similar to those of healthy adults, these results can likely be extended to other populations, although future studies are needed to confirm this.
“…Further, as per recommendations by the International Society for Clinical Densitometry (ISCD), we computed the least significant change (LSC). (24)(25)(26)…”
Repositioning error in longitudinal high-resolution peripheral-quantitative computed tomography (HR-pQCT) imaging can lead to different bone volumes being assessed over time. To identify the same bone volumes at each time point, image registration is used. While crosssectional area image registration corrects axial misalignment, 3D registration additionally corrects rotations. Other registration methods involving matched angle analysis (MA) or boundary transformations (3D-TB) can be used to limit interpolation error in 3D-registering micro-finite-element data. We investigated the effect of different image registration methods on short-term in vivo precision in adults with osteogenesis imperfecta, a collagen-related genetic disorder resulting in low bone mass, impaired quality, and increased fragility. The radii and tibiae of 29 participants were imaged twice on the same day with full repositioning. We compared the precision error of different image registration methods for density, microstructural, and micro-finite-element outcomes with data stratified based on anatomical site, motion status, and scanner generation. Regardless of the stratification, we found that image registration improved precision for total and trabecular bone mineral densities, trabecular and cortical bone mineral contents, area measurements, trabecular bone volume fraction, separation, and heterogeneity, as well as cortical thickness and perimeter. 3D registration marginally outperformed cross-sectional area registration for some outcomes, such as trabecular bone volume fraction and separation. Similarly, precision of micro-finite-element outcomes was improved after image registration, with 3D-TB and MA methods providing greatest improvements. Our regression model confirmed the beneficial effect of image registration on HR-pQCT precision errors, whereas motion had a detrimental effect on precision even after image registration. Collectively, our results indicate that 3D registration is recommended for longitudinal HR-pQCT imaging in adults with osteogenesis imperfecta. Since our precision errors are similar to those of healthy adults, these results can likely be extended to other populations, although future studies are needed to confirm this.
“…The 8% and 7% ROI include both cortical and trabecular bones and exclude the growth plate in most children [ 28 , 30 ]. This protocol was used throughout the mixed-longitudinal UBC Healthy Bones Study [ 1 , 3 , 36 – 42 ], for developing normative data for XCTI in children and adolescents [ 9 ], and by other research groups [ 43 – 46 ]. Fig.…”
Section: Current Pediatric Hr-pqct Protocolsmentioning
confidence: 99%
“…Apparent modulus [MPa] is also often reported, which is the average stress divided by the applied strain. Ultimate stress [MPa] has been reported in several pediatric studies [ 1 , 3 , 41 – 43 ] and is related to the apparent modulus via an empirically derived equation against experimentally determined bone strength [ 15 ]. Lastly, the ratio of force carried by each bone compartment (i.e., trabecular or cortical) as well as specific sub-regions (i.e., distal or proximal) can be estimated.…”
Section: Finite Element Analysismentioning
confidence: 99%
“…Inputs are usually identified by validating against experimentally determined measures of bone strength or local strains from adult cadaveric bone. Acquiring pediatric cadaveric specimens is extremely difficult; thus, pediatric studies reporting μFE-based parameters currently apply the same material properties and failure criterion as adult studies (e.g., Poisson’s ratio of 0.3 and elastic modulus of 10,000 MPa) [ 1 , 3 , 9 , 39 , 41 – 43 , 59 – 63 ]. Adult material properties are assumed to be homogeneous and constant; this assumption may not be true during growth, as tissue density is variable and changes with age.…”
Purpose of Review
The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT).
Recent Findings
Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each. Limiting protocol variation will enhance the uniformity of results and increase our ability to compare study results between different research groups. We outline special cases along with tips and tricks for acquiring and processing scans to minimize motion artifacts and account for growing bone.
Summary
The recommendations in this review are intended to help researchers perform HR-pQCT imaging in pediatric populations and extend our collective knowledge of bone structure, architecture, and strength during the growing years.
“…HR-pQCT has been shown to be a reliable method for evaluating changes in bone strength, but future studies are needed to determine its usefulness fully [ 29 ]. Furthermore, HR-pQCT and its associated image analysis methods and software were designed and validated for mature bone, but it is yet to be validated on immature bone [ 30 ]. By the same token, evidence is still emerging on whether the distal radius or tibia is the ideal site for monitoring therapy directed toward osteoporotic patients susceptible to lumbar spine or proximal femur fractures [ 5 ].…”
Until recently, the evaluation of bone health and fracture risk through imaging has been limited to dual-energy X-ray absorptiometry (DXA) and plain radiographs, with a limited application in the athletic population. Several novel imaging technologies are now available for the clinical assessment of bone health, including bone injury risk and healing progression, with a potential for use in sports medicine. Among these imaging modalities is high-resolution peripheral quantitative computed tomography (HR-pQCT) which is a promising technology that has been developed to examine the bone microarchitecture in both cortical and trabecular bone at peripheral anatomical sites. Technologies that do not expose patients to ionizing radiation are optimal, particularly for athletes who may require frequent imaging. One such alternative is diagnostic ultrasound, which is preferable due to its low cost and lack of radiation exposure. Furthermore, ultrasound, which has not been a common imaging modality for monitoring fracture healing, has been shown to potentially demonstrate earlier signs of union compared to conventional radiographs, including callus mineralization and density at the healing site. Through the use of conventional magnetic resonance imaging (MRI), finite element analysis (FEA) can be used to simulate the structural and mechanical properties of bone. On the other hand, the ultrashort echo time (UTE) MRI can evaluate cortical bone quality by detecting water bound to the organic bone matrix and free water, providing important information about bone porosity. Several novel bone imaging techniques originally developed for osteoporosis assessment have great potential to be utilized to improve the standard of care in bone fracture risk assessment and healing in sports medicine with much greater precision and less adverse radiation exposure.
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