Few studies have analyzed the microstructural properties of bone in cases of Osteogenenis Imperfecta (OI), or ‘brittle bone disease’. Current approaches mainly focus on bone mineral density measurements as an indirect indicator of bone strength and quality. It has been shown that bone strength would depend not only on composition but also structural organization. This study aims to characterize 3D structure of the cortical bone in high-resolution micro CT images. A total of 40 bone fragments from 28 subjects (13 with OI and 15 healthy controls) were imaged using micro tomography using a synchrotron light source (SRµCT). Minkowski functionals - volume, surface, curvature, and Euler characteristics - describing the topological organization of the bone were computed from the images. The features were used in a machine learning task to classify between healthy and OI bone. The best classification performance (mean AUC – 0.96) was achieved with a combined 4-dimensional feature of all Minkowski functionals. Individually, the best feature performance was seen using curvature (mean AUC - 0.85), which characterizes the edges within a binary object. These results show that quantitative analysis of cortical bone microstructure, in a computer-aided diagnostics framework, can be used to distinguish between healthy and OI bone with high accuracy.
Osteogenesis imperfecta (OI) is a genetic disorder leading to increased bone fragility. Recent work has shown that the hierarchical structure of bone plays an important role in determining its mechanical properties and resistance to fracture. The current study represents one of the first attempts to characterize the 3D structure and composition of cortical bone in OI at the micron-scale. A total of 26 pediatric bone fragments from 18 individuals were collected during autopsy (Nc=5) or routing orthopaedic procedures (NOI=13) and imaged by microtomography with a synchrotron light source (SRμCT) for several microstructural parameters including cortical porosity (Ca.V/TV), canal surface to tissue volume (Ca.S/TV), canal diameter (Ca.Dm), canal separation (Ca.Sp), canal connectivity density (Ca.ConnD), and volumetric tissue mineral density (TMD). Results indicated significant differences in all imaging parameters between pediatric controls and OI tissue, with OI bone showing drastically increased cortical porosity, canal diameter, and connectivity. Preliminary mechanical testing revealed a possible link between cortical porosity and strength. Together these results suggest that the pore network in OI contributes greatly to its reduced mechanical properties.
The X-ray micro-Tomography Facility at the Advanced Light Source has been in operation since 2004. The source is a superconducting bend magnet of critical energy 11.5 keV; photon energy coverage is 8-45 KeV in monochromatic mode, and a filtered white light option yields useful photons up to 50 keV. A user-friendly graphical user interface allows users to collect tomographic and radiographic data sets with options including tiled and time series data sets. We will focus on recent projects that utilize sample environments for in-situ imaging. These environments include a high pressure triaxial flow cell which has allowed study of supercritical CO2 transport through brine-saturated sandstone at pressures typical of in-situ conditions for subsurface CO2 sequestration and water transportation within live plants.
Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely
but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of
human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric
analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT)
system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine
surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of
bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity
density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently
higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such
as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed
strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone
testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling
possibilities for the future of OI bone assessment.
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