Relationships of trabecular bone structure with quantitative ultrasound parameters: in vitro study on human proximal femur using transmission and backscatter measurements.

The present study was designed to assess the relationships between QUS parameters and bone density or microarchitecture on samples of human femoral trabecular bone. The normalized slope of the frequency-dependent attenuation (nBUA), the speed of sound (SOS) and the broadband ultrasound backscatter coefficient (BUB) were measured on 37 specimens of pure trabecular bones removed from upper parts of fresh human femurs. Bone mineral density (BMD) was assessed using a clinical scanner. Finally, 8 mm diameter cylindrical cores were extracted from the specimens and their microarchitecture was reconstructed after synchrotron radiation microtomography experiments (isotropic resolution of 10 microm). A large number of microarchitectural parameters were computed, describing morphology, connectivity and geometry of the specimens. BMD correlated with all the microarchitectural parameters and the number of significant correlations was found among the architectural parameters themselves. All QUS parameters were significantly correlated to BMD (R=0.83 for nBUA, R=0.81 for SOS and R=0.69 for BUB) and to microarchitectural parameters (R=-0.79 between nBUA and Tb.Sp, R=-0.81 between SOS and Tb.Sp, R=-0.65 between BUB and BS/BV). Using multivariate model, it was found that microstructural parameters adds 10%, 19%, and 4% to the respective BMD alone contribution for the three variables BUA, SOS and BUB. Moreover, the RMSE was reduced by up to 50% for SOS, by up to 21% for nBUA and up to 11% when adding structural variables to BMD in explaining QUS results. Given the sample, which is not osteoporosis-enriched, the added contribution is quite substantial. The variability of SOS was indeed completely explained by a multivariate model including BMD and independent structural parameters (R(2)=0.94). The inverse problem on the data presented here has been addressed using simple and multiple linear regressions. It was shown that the predictions (in terms of R(2) or RMSE) of microarchitectural parameters was not enhanced when combining 2 or 3 QUS in multiple linear regressions compared to the prediction obtained with one QUS parameter alone. The best model was found for the prediction of Tb.Th() from BUA (R(2)=0.58, RMSE=17 microm). Given the high values of RMSE, these linear models appear of limited clinical value, suggesting that appropriate models have to be derived in order to solve the inverse problem. In this regard, a very interesting multivariate model was found for nBUA and BUB with Tb.Th and Tb.N, in agreement with single scattering theories by random medium. However, the source of residual variability of nBUA and BUB (15% and 45% respectively) remained unexplained.

Influence of the precision of spectral backscatter measurements on the estimation of scatterers size in cancellous bone.

The goal of this study is to propose a model for the ultrasonic frequency-dependent backscatter coefficient in femoral cancellous bone. This model has been developed with success to predict backscatter in human calcaneal bone [Jenson, Ultr. Med. Biol. 2003]. A weak scattering model is used and the backscatter coefficient is expressed in terms of a Gaussian autocorrelation function of the medium. The backscatter coefficient is computed and comparison is made with experimental data for 37 specimens and for frequency ranging from 0.4 to 1.2 MHz. An excellent agreement between experimental data and predictions is found for both the magnitude and the frequency-dependence of the backscatter coefficient. Then, a nonlinear regression is performed for each specimen, and the mean trabecular thickness is estimated. Experimental data and theoretical predictions are averaged over the 37 specimens. We also find a close agreement between theoretical predictions obtained using the Gaussian autocorrelation function (scatterer size=134+/-15 microm) and the mean trabecular thickness (Tb.Th=132+/-12 microm) derived from the analysis of bone 3-D micro-architecture using high-resolution micro-tomography. However, the correlation between individual experimental and estimated Tb.Th values is moderate (R(2)=0.44). The performance of the estimator are limited mainly by two factors: interference noise due to random positioning of the scatterers and attenuation. We show that the fundamental limitation of our estimator due to the speckle noise is around 5 microm for trabecular thickness estimation. This limitation is lower than the observed biological variability which is around 30 microm and should not be a limiting factor for individual prediction. A second limitation is the tremendous attenuation encountered in highly scattering media such as cancellous bone, which results in highly damped backscatter signals. The compensation for attenuation is difficult to perform, and it may be a critical point that limits the precision of the estimator.

Numerical simulation of wave propagation in cancellous bone.

Numerical simulation of wave propagation is performed through 31 3D volumes of trabecular bone. These volumes were reconstructed from high synchrotron microtomography experiments and are used as the input geometry in a simulation software developed in our laboratory. The simulation algorithm accounts for propagation into both the saturating fluid and bone but absorption is not taken into account. We show that 3D simulation predicts phenomena observed experimentally in trabecular bones : linear frequency dependence of attenuation, increase of attenuation and speed of sound with the bone volume fraction, negative phase velocity dispersion in most of the specimens, propagation of fast and slow wave depending on the orientation of the trabecular network compared to the direction of propagation of the ultrasound. Moreover, the predicted attenuation is in very close agreement with the experimental one measured on the same specimens. Coupling numerical simulation with real bone architecture therefore provides a powerful tool to investigate the physics of ultrasound propagation in trabecular structures.

In vitro ultrasonic characterization of human cancellous femoral bone using transmission and backscatter measurements: relationships to bone mineral density.

Thirty-eight slices of pure trabecular bone 1-cm thickness were extracted from human proximal femurs. A pair of 1-MHz central frequency transducers was used to measure quantitative ultrasound (QUS) parameters in transmission [normalized broadband ultrasound attenuation (nBUA), speed of sound (SOS)] and in backscatter [broadband ultrasound backscatter (BUB)]. Bone mineral density (BMD) was measured using clinical x-ray quantitative computed tomography. Site-matched identical region of interest (ROIs) of 7 x 7 mm2 were positioned on QUS and QCT images. This procedure resulted in 605 ROIs for all the specimens data pooled together. The short-term precision of the technique expressed in terms of CV was found to be 2.3% for nBUA, 0.3% for SOS and 4.5% for BUB. Significant linear correlation between QUS and BMD were found for all the 605 ROIs pooled, with r2 values of 0.73, 0.77, and 0.58 for nBUA, SOS, and BUB, respectively (all p < 0.05). For the BUB, the best regression was obtained with a polynomial fit of second order (r2 = 0.63). An analysis of measurements errors was developed. It showed that the residual variability of SOS is almost completely predicted by measurements errors, which is not the case for BUA and BUB, suggesting a role for micro-architecture in the determination of BUA and BUB.

Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K.

Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.