Bi-Directional Axial Transmission measurements applied in a clinical environment.

Accurate measurement of cortical bone parameters may improve fracture risk assessment and help clinicians on the best treatment strategy. Patients at risk of fracture are currently detected using the current X-Ray gold standard DXA (Dual XRay Absorptiometry). Different alternatives, such as 3D X-Rays, Magnetic Resonance Imaging or Quantitative Ultrasound (QUS) devices, have been proposed, the latter having advantages of being portable and sensitive to mechanical and geometrical properties. The objective of this cross-sectional study was to evaluate the performance of a Bi-Directional Axial Transmission (BDAT) device used by trained operators in a clinical environment with older subjects. The device, positioned at one-third distal radius, provides two velocities: VFAS (first arriving signal) and VA0 (first anti-symmetrical guided mode). Moreover, two parameters are obtained from an inverse approach: Ct.Th (cortical thickness) and Ct.Po (cortical porosity), along with their ratio Ct.Po/Ct.Th. The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. One hundred and six patients (81 women, 25 men) from Marien Hospital and St. Anna Hospital (Herne, Germany) were included in this study. Age ranged from 41 to 95 years, while body mass index (BMI) ranged from 16 to 47 kg.m-2. Three groups were considered: 79 non-fractured patients (NF, 75±13years), 27 with non-traumatic fractures (F, 80±9years) including 14 patients with non-vertebral fractures (NVF, 84±7years). Weak to moderate significant Spearman correlations (R ranging from 0.23 to 0.53, p < 0.05) were found between ultrasound parameters and age, BMI. Using multivariate Partial Least Square discrimination analyses with Leave-One-Out Cross-Validation (PLS-LOOCV), we found the combination of VFAS and the ratio Ct.Po/Ct.Th to be predictive for all non traumatic fractures (F) with the odds ratio (OR) equals to 2.5 [1.6-3.4] and the area under the ROC curve (AUC) equal to 0.63 [0.62-0.65]. For the group NVF, combination of four parameters VA0. Ct.Th, Ct.Po and Ct.Po/Ct.Po, along with age provides a discrimination model with OR and AUC equals to 7.5 [6.0-9.1] and 0.75 [0.73-0.76]. When restricted to a smaller population (87 patients) common to both BDAT and DXA, BDAT ORs and AUCs are comparable or slightly higher to values obtained with DXA. The fracture risk assessment by BDAT method in older patients, in a clinical setting, suggests the benefit of the affordable and transportable device for the routine use.

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.

The aim of this study was to estimate cortical porosity (Ct.Po) and cortical thickness (Ct.Th) using 500-kHz bi-directional axial transmission (AT). Ct.ThAT and Ct.PoAT were obtained at the tibia in 15 patients from a 2-D transverse isotropic free plate model fitted to measured guided wave dispersion curves. The velocities of the first arriving signal (υFAS) and A0 mode (υA0) were also determined. Site-matched peripheral quantitative computed tomography (pQCT) provided volumetric cortical bone mineral density (Ct.vBMDpQCT) and Ct.ThpQCT. Good agreement was found between Ct.ThAT and Ct.ThpQCT (R2 = 0.62, root mean square error [RMSE] = 0.39 mm). Ct.vBMDpQCT correlated with Ct.PoAT (R2 = 0.57), υFAS (R2 = 0.43) and υA0 (R2 = 0.28). Furthermore, a significant correlation was found between AT and distal high-resolution pQCT. The measurement ofcortical parameters at the tibia using guided waves might improve the prediction of bone fractures in a cost-effective and radiation-free manner.

Ex vivo cortical porosity and thickness predictions at the tibia using full-spectrum ultrasonic guided-wave analysis.

The estimation of cortical thickness (Ct.Th) and porosity (Ct.Po) at the tibia using axial transmission ultrasound was successfully validated ex vivo against site-matched micro-computed tomography. The assessment of cortical parameters based on full-spectrum guided-wave analysis might improve the prediction of bone fractures in a cost-effective and radiation-free manner. PURPOSE: Cortical thickness (Ct.Th) and porosity (Ct.Po) are key parameters for the identification of patients with fragile bones. The main objective of this ex vivo study was to validate the measurement of Ct.Po and Ct.Th at the tibia using a non-ionizing, low-cost, and portable 500-kHz ultrasound axial transmission system. Additional ultrasonic velocities and site-matched reference parameters were included in the study to broaden the analysis. METHODS: Guided waves were successfully measured ex vivo in 17 human tibiae using a novel 500-kHz bi-directional axial transmission probe. Theoretical dispersion curves of a transverse isotropic free plate model with invariant matrix stiffness were fitted to the experimental dispersion curves in order to estimate Ct.Th and Ct.Po. In addition, the velocities of the first arriving signal (υFAS) and A0 mode (υA0) were measured. Reference Ct.Po, Ct.Th, and vBMD were obtained from site-matched micro-computed tomography. Scanning acoustic microscopy (SAM) provided the acoustic impedance of the axial cortical bone matrix. RESULTS: The best predictions of Ct.Po (R2 = 0.83, RMSE = 2.2%) and Ct.Th (R2 = 0.92, RMSE = 0.2 mm, one outlier excluded) were obtained from the plate model. The second best predictors of Ct.Po and Ct.Th were vBMD (R2 = 0.77, RMSE = 2.6%) and υA0 (R2 = 0.28, RMSE = 0.67 mm), respectively. CONCLUSIONS: Ct.Th and Ct.Po were accurately predicted at the human tibia ex vivo using a transverse isotropic free plate model with invariant matrix stiffness. The model-based predictions were not further enhanced when we accounted for variations in axial tissue stiffness as reflected by the acoustic impedance from SAM.

Optical protein detection based on magnetic clusters rotation.

In this paper we present a simple method to quantify aggregates of 200nm magnetic particles. This method relies on the optical and magnetic anisotropy of particle aggregates, whereas dispersed particles are optically isotropic. We orientate aggregates by applying short pulses of a magnetic field, and we measure optical density variation directly linked to this reorientation. By computing the scattering efficiency of doublets and singlets, we demonstrate the absolute quantification of a few % of doublets in a well dispersed suspension. More generally, these optical variations are related to the aggregation state of the sample. This method can be easily applied to an agglutination assay, where target proteins induce aggregation of colloidal particles. By observing only aligned clusters, we increase sensitivity and we reduce the background noise as compared to a classical agglutination assay: we obtain a detection limit on the C-reactive protein of less than 3pM for a total assay time of 10min.