Targeting cortical bone quality by ultrasound biomarkers - relations to porosity, stiffness and strength
Final Report Abstract
A systematic multiscale, multimodal, and multisite survey of bone properties in tibia and proximal femur and their associations with proximal femur stiffness and ultimate strength has been conducted on a set of left/right tibia/femur pairs from 20 human donors. High-resolution peripheral quantitative computed tomography of the proximal femora (voxel size 30 µm) was used to develop individualized FE models for the prediction macroscopic proximal femur stiffness and strength. Meso- and microscale information of cortical structure, stiffness, and strength in femoral neck, proximal femur shaft, and tibia midshaft were assessed by means of microcomputed tomography, scanning acoustic microscopy, resonant ultrasound spectroscopy, and destructive mechanical testing. In addition to established in-vivo diagnostic imaging modalities (DXA, pQCT) novel quantitative ultrasound technologies were developed and applied for through-transmission, axial transmission, refraction and backscatter measurements. From these measurements, cortical thickness, porosity, pore size, and pore density were derived. All derived data were compiled in a web-based database with on-demand open access. The results of this study demonstrate that • ultrasound velocities in the longitudinal and transverse directions are associated cortical strength and cortical porosity, • cortical thickness and porosity can be assessed reliably using axial transmission and refraction ultrasound, • reduced cortical thickness, increased porosity, and the prevalence of large pores in the tibia are associated with various cortical and trabecular deteriorations in the femoral neck, • reduced cortical thickness and prevalence of large pores in the tibia is associated with reduced hip strength, • the prevalence of large pores could explain up to 17% of the ultimate force not explained by DXA, • cortical pore size can be assessed from the spectral ultrasound backscatter response. In summary, the potential of these new non-ionizing diagnostic modalities and the derived biomarkers have been shown in vitro, and for the axial transmission of guided waves also in vivo. The possibility to assess multiple fracture-risk related bone properties without ionizing radiation instead of one parameter using x-rays is anticipated to open new perspectives for an early identification of patients at risk, the development of improved treatment stratification and monitoring, and thereby the prevention of bone fractures. Some of these new in-vivo techniques have already been commercialized. The other ones will be used in clinical trials and will be further developed as medical products.
Publications
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Computational study of the effect of cortical porosity on ultrasound wave propagation in healthy and osteoporotic long bones. Materials. 2016; 9, 205
Potsika VT, Grivas KN, Gortsas T, Iori G, Protopappas VC, Raum K, Polyzos D, Fotiadis DI
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Elasticity-density and viscoelasticity-density relationships at the tibia mid-diaphysis assessed from resonant ultrasound spectroscopy measurements. Biomech Model Mechanobiol. 2016;15(1):97-109
Bernard S, Schneider J, Varga P, Laugier P, Raum K, Grimal Q
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A critical assessment of the in-vitro measurement of cortical bone stiffness with ultrasound. Ultrasonics. 2017;80:119-26
Peralta L, Cai X, Laugier P, Grimal Q
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Quantification of stiffness measurement errors in resonant ultrasound spectroscopy of human cortical bone. J Acoust Soc Am. 2017;142(5):2755
Cai X, Peralta L, Gouttenoire PJ, Olivier C, Peyrin F, Laugier P, Grimal Q
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BMD-based assessment of local porosity in human femoral cortical bone. Bone. 2018;114:50-61
Iori G, Heyer F, Kilappa V, Wyers C, Varga P, Schneider J, Grasel M, Wendlandt R, Barkmann R, van den Bergh, Raum K
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Ex vivo cortical porosity and thickness predictions at the tibia using full-spectrum ultrasonic guided-wave analysis. Arch Osteoporos. 2019;14(1):21
Schneider J, Iori G, Ramiandrisoa D, Hammami M, Grasel M, Chappard C, Barkmann, R, Laugier, P, Grimal, Q, Minonzio, JG, Raum, K
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In Vivo Measurements of Cortical Thickness and Porosity at the Proximal Third of the Tibia Using Guided Waves: Comparison with Site-Matched Peripheral Quantitative Computed Tomography and Distal High-Resolution Peripheral Quantitative Computed Tomography. Ultrasound Med Biol. 2019
Schneider J, Ramiandrisoa D, Armbrecht G, Ritter Z, Felsenberg D, Raum K, Minonzio, JG
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Large cortical bone pores in the tibia are associated with proximal femur strength, PlosOne, 2019;14(4):e0215405
Iori G, Schneider J, Reisinger A, Heyer F, Peralta L, Wyers C, Gräsel M, Barkmann R, Glüer CC, van den Bergh J, Pahr D, Raum K
