Targeting cortical bone state by quantitative in-vivo ultrasound imaging

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Osteoporosis (OP) is one of the most important global health problems of our aging population. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are not diagnosed as osteoporotic according to the current gold standard to predict bone status (bone mineral density BMD measured with dual energy x-ray absorptiometry DXA). The mechanical integrity of cortical bone (~80% of the human skeleton mass) is a key factor of bone strength at several anatomical sites. As a consequence of an unbalanced intracortical remodeling some large pores appear, leading to a characteristic change of the pore size distribution, increased cortical porosity (Ct.Po) and reduced thickness (Ct.Th). These structural alterations together with compromised viscoelastic tissue matrix properties dramatically reduce bone strength. In a previous bi-national DFG-ANR project “TaCoSound” (2015-2018) a systematic ex-vivo survey of bone properties in human tibia and proximal femur and their associations with proximal femur stiffness and ultimate strength has been conducted. During the past 2 years, the applicant and international collaboration partners proposed original quantitative in-vivo ultrasound US imaging modalities to i) assess sound velocity (resembling Ct.Po and viscoelastic tissue properties) and Ct.Th from refraction-corrected ultrasound images of the cortical bone shell, and ii) to assess from the "spectral fingerprint" of acoustic waves backscattered from cortical pores the respective pore size distribution. The present project builds on TaCoSound and recent findings suggesting that the majority (82%) of variations of proximal femur strength can be predicted by Ct.Th (69%) and the prevalence of large pores (18%) in the tibia midshaft. Promising ex-vivo and preliminary in-vivo results demonstrate that - for the first time in humans – cortical pore size distribution can be assessed noninvasively and together with attenuation provides superior fracture discrimination performance compared to DXA. However, improved image reconstruction algorithms and a more comprehensive backscatter model need to be developed prior a broad clinical application.TaCoSoundInVivo aims at the development of an US imaging modality that combines robust and spatially resolved estimations of macro- and microstructural as well as viscoelastic properties of cortical bone and will apply it on a representative cohort of healthy, osteopenic and osteoporotic people. The fracture discrimination performance of US parameters will be benchmarked i) ex-vivo on well characterized bone phantoms and ii) in-vivo by means of site-matched high-resolution peripheral quantitative computed tomography (HRpQCT). We anticipate to observe age-, gender and disease associated alterations, and that multiple US parameters can identify people at increased fracture risk, particularly in people with normal or reduced BMD.