Stefanie Dencks

Femur ultrasound (FemUS)—first clinical results on hip fracture discrimination and estimation of femoral BMD

SummaryA quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis.IntroductionDual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance.MethodsUsing the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed.ResultsHip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R2 up to 0.72 and a residual error of about one half of a T-score in BMD.ConclusionsQUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.

A device for in vivo measurements of quantitative ultrasound variables at the human proximal femur

Quantitative ultrasound (QUS) at the calcaneus has similar power as a bone mineral density (BMD)- measurement using DXA for the prediction of osteoporotic fracture risk. Ultrasound equipment is less expensive than DXA and free of ionizing radiation. As a mechanical wave, QUS has the potential of measuring different bone properties than dual X-ray absorptiometry (DXA,) which depends on X-ray attenuation and might be developed into a tool of comprehensive assessment of bone strength. However, site- specific DXA at the proximal femur shows best performance in the prediction of hip fractures. To combine the potential of QUS with measurements directly at the femur, we developed a device for in vivo QUS measurements at this site. Methods comprise ultrasound transmission through the bone, reflection from the bone surface, and backscat- ter from the inner trabecular structure. The complete area of the proximal femur can be scanned except at the femoral head, which interferes with the ilium. To avoid edge artifacts, a subregion of the proximal femur in the trochanteric region was selected as measurement region. First, in vivo measurements demonstrate a good signal to noise ratio and proper depiction of the proximal femur on an attenuation image. Our results demonstrate the feasibility of in vivo measurements. Further improvements can be expected by refinement of the scanning technique and data evaluation method to enhance the potential of the new method for the estimation of bone strength.

In Vivo Measurements of Ultrasound Transmission Through the Human Proximal Femur

Quantitative ultrasound (QUS) measurements can be used to estimate osteoporotic fracture risk. The commonly used variables are the speed of sound (SOS) and the frequency dependent sound attenuation (broadband ultrasound attenuation, [BUA]) of a wave propagating through the bone, preferably the calcaneus. The technology, so far, is less suitable for direct measurement in vivo at the spine or the femur for prediction of bone mineral density (BMD) or fracture risk at the main osteoporotic fracture sites. To improve the clinical performance of QUS, we built a device for direct QUS measurements at the human femur in vivo. In vivo images of ultrasound transmission at one of the main fracture sites, the proximal femur, could be acquired. The estimated precision of SOS measurements of 0.5% achieved at the femur is comparable with the precision of peripheral QUS devices.

Model-based estimation of quantitative ultrasound variables at the proximal femur

To improve the prediction of the osteoporotic fracture risk at the proximal femur we are developing a scanner for quantitative ultrasound (QUS) measurements at this site. Due to multipath transmission in this complex shaped bone, conventional signal processing techniques developed for QUS measurements at peripheral sites frequently fail. Therefore, we propose a model-based estimation of the QUS variables and analyze the performance of the new algorithm. Applying the proposed method to QUS scans of excised proximal femurs increased the fraction of evaluable signals from approx. 60% (using conventional algorithms) to 97%. The correlation of the standard QUS variables broadband ultrasound attenuation (BUA) and speed of sound (SOS) with the established variable bone mineral density (BMD) reported in previous studies is maintained (BUA/BMD: r2 = 0.69; SOS/BMD: r2= 0.71; SOS+BUA/BMD: r2 = 0.88). Additionally, different wave types could be clearly detected and characterized in the trochanteric region. The ability to separate superimposed signals with this approach opens up further diagnostic potential for evaluating waves of different sound paths and wave types through bone tissue.

Estimation of multipath transmission parameters for quantitative ultrasound measurements of bone

When applying quantitative ultrasound (QUS) measurements to bone for predicting osteoporotic fracture risk, the multipath transmission of sound waves frequently occurs. In the last 10 years, the interest in separating multipath QUS signals for their analysis awoke, and led to the introduction of several approaches. Here, we compare the performances of the two fastest algorithms proposed for QUS measurements of bone: the modified least-squares Prony method (MLSP), and the space alternating generalized expectation maximization algorithm (SAGE) applied in the frequency domain. In both approaches, the parameters of the transfer functions of the sound propagation paths are estimated. To provide an objective measure, we also analytically derive the Cramér-Rao lower bound of variances for any estimator and arbitrary transmit signals. In comparison with results of Monte Carlo simulations, this measure is used to evaluate both approaches regarding their accuracy and precision. Additionally, with simulations using typical QUS measurement settings, we illustrate the limitations of separating two superimposed waves for varying parameters with focus on their temporal separation. It is shown that for good SNRs around 100 dB, MLSP yields better results when two waves are very close. Additionally, the parameters of the smaller wave are more reliably estimated. If the SNR decreases, the parameter estimation with MLSP becomes biased and inefficient. Then, the robustness to noise of the SAGE clearly prevails. Because a clear influence of the interrelation between the wavelength of the ultrasound signals and their temporal separation is observable on the results, these findings can be transferred to QUS measurements at other sites. The choice of the suitable algorithm thus depends on the measurement conditions.

Model-based parameter estimation in the frequency domain for Quantitative Ultrasound measurement of bone

From Quantitative Ultrasound (QUS) measurements of excised bone samples or intact bones, the multipath transmission of sound waves is a known phenomenon. It has been shown that in the case of superimposed signal components the calculation of the standard QUS parameters Speed-of-Sound (SOS) and Broadband Ultrasound Attenuation (BUA) becomes problematic. Recently, we adapted a model-based parameter estimation in the time domain to allow for evaluating single signal components. Now, we have transferred the parameter estimation into the frequency domain to make its application more flexible. Through applying the model-based signal separation, the uncertainty in computing SOS and BUA is substantially reduced.

Needle visibility for deep punctures with curved arrays

Sonography is the standard technique for monitoring local punctures with needles. Using convex arrays for deeper puncture targets, an increasingly poorer needle visibility is expected. However, it is observed that the needle reappears for large incidence angles of the ultrasound wave to the needle. It is investigated, whether this effect is caused by resonant scattering of the needle. Measurements and simulations demonstrate that resonant scattering occurs for angles of incidence larger than the Rayleigh-angle caused by the excitation of helical guided waves propagating circumferentially and axially. This effect could be exploited to improve needle visibility by adaptive beamforming.

Signal Separation in the Frequency Domain for Quantitative Ultrasound Measurements of Bone

To improve the prediction of the osteoporotic fracture risk at the proximal femur a scanner for Quantitative Ultrasound (QUS) measurements at this site has been developed. Due to the multipath transmission in this complex shaped bone conventional signal processing techniques developed for QUS measurements at peripheral sites frequently failed. Applying a model-based signal separation in the time domain allowed for successfully evaluating both, ex vivo and in vivo measurements. However, this signal separation is restricted to Gaussian modulated cosine pulses. To overcome this limitation we extended the method for its application to arbitrary signals by transferring the parameter estimation into the frequency domain.

2A-6 Optimization Algorithm for Improved Quantitative Ultrasound Signal Processing at the Proximal Femur

To improve the prediction of the osteoporotic fracture risk at the proximal femur we are developing a scanner for quantitative ultrasound (QUS) measurements at this site. Due to multipath transmission in this complex shaped bone conventional signal processing techniques developed for QUS measurements at peripheral sites frequently fail. Applying a model-based estimation method to quantitative ultrasound scans of excised proximal femurs the fraction of evaluable signals can be increased from approx. 60% (using conventional algorithms) to 95%. The correlation of the standard QUS variables broadband ultrasound attenuation (BUA) and speed-of-sound (SOS) with the established variable bone mineral density (BMD) reported in previous studies is maintained (r 2 BUA/BMD = 0.69, r2 SOS/BMD = 0.82). Because of its ability to separate superimposed signals this approach opens up further diagnostic potential by evaluating the information of waves of different sound paths through the bone

Evaluation of bubble tracking algorithms for super-resolution imaging of microvessels

Ultrasound super-resolution imaging of microvessels and quantifying flow velocities have been proposed lately by several authors [1,2,3]. The standard approach is tracking microbubbles (MB) by searching for the nearest neighbor (NN) detection in consecutive frames. In [3] a Markov chain Monte Carlo data association (MCMCDA) algorithm was implemented to handle more complex vessel morphologies and/or higher bubble concentrations. Here, we investigate the performance of the algorithms in random vessel trees with known ground truth which simulate typical measurement conditions when imaging tumors in vivo. By this, we evaluate the quality of vessel reconstruction, the accuracy of velocity estimates and the influence of microbubble concentration. We demonstrate advantages of the MCMCDA in estimation accuracy of tracks and velocities in more complex vessel morphologies as they are expected in tumor microvasculature.