J. Töyräs

Ultrasound Backscatter Imaging Provides Frequency-Dependent Information on Structure, Composition and Mechanical Properties of Human Trabecular Bone

The strength as well as the acoustic properties of trabecular bone are determined by its structure and composition. Consequently, tissue structure and compositional properties also affect the ultrasound propagation in bone. The diagnostic potential of ultrasound has not been fully exploited in clinical quantitative ultrasound devices. The aim of this study was to investigate the ability of quantitative ultrasound pulse-echo imaging, conducted over a broad range of frequencies (1 to 5 MHz), to predict the mechanics, composition and microstructure of trabecular bone. Ultrasound reflection and backscatter parameters correlated significantly with the ultimate strength of the trabecular bone and the bone volume fraction (r=0.76-0.90, n=20, p<0.01). Ultrasound backscatter associated significantly (independently of bone structure or mineral content) with the collagen content of the bone matrix (r=0.75, r(adjusted)=0.66, p<0.01). Interestingly, the applied ultrasound frequency seemed to relate the sensitivity of ultrasound backscatter to different properties of trabecular bone. At frequencies ranging from 1 to 3.5 MHz, the ultrasound backscatter associated significantly with the tissue mechanical and structural parameters. At 5MHz, the composition of the bone matrix was a more significant determinant of the measured backscatter. This study provides useful information for optimizing the use of pulse-echo measurements, and thereby further emphasizes the diagnostic potential of the ultrasound backscatter measurements of trabecular bone.

Multi-site bone ultrasound measurements in elderly women with and without previous hip fractures

SummaryAbout 75% of patients suffering from osteoporosis are not diagnosed. This study describes a multi-site bone ultrasound method for osteoporosis diagnostics. In comparison with axial dual energy X-ray absorptiometry (DXA), the ultrasound method showed good diagnostic performance and could discriminate fracture subjects among elderly females.IntroductionAxial DXA, the gold standard diagnostic method for osteoporosis, predicts fractures only moderately. At present, no reliable diagnostic methods are available at the primary health care level. Here, a multi-site ultrasound method is proposed for osteoporosis diagnostics.MethodsThirty elderly women were examined using the ultrasound backscatter measurements in proximal femur, proximal radius, proximal and distal tibia in vivo. First, we predicted the areal bone mineral density (BMD) at femoral neck by ultrasound measurements in tibia combined with specific subject characteristics (density index, DI) and, second, we tested the ability of ultrasound backscatter measurements at proximal femur to discriminate between individuals with previously fractured hips from those without fractures. Areal BMD was determined by axial DXA.ResultsCombined ultrasound parameters, cortical thickness at distal and proximal tibia, with age and weight of the subject, provided a significant estimate of BMDneck (ru2009=u20090.86, pu2009<u20090.001, nu2009=u200930). When inserted into FRAX (World Health Organization fracture risk assessment tool), the DI indicated the same treatment proposal as the BMDneck with 86% sensitivity and 100% specificity. The receiver operating characteristic analyses, with a combination of ultrasound parameters and patient characteristics, discriminated fracture subjects from the controls similarly as the model combining BMDneck and patient characteristics.ConclusionsFor the first time, ultrasound backscatter measurements of proximal femur were conducted in vivo. The results indicate that ultrasound parameters, combined with patient characteristics, may provide a means for osteoporosis diagnostics.

Ultrasonic assessment of cortical bone thickness in vitro and in vivo

In osteoporosis, total bone mass decreases and the thickness of the cortical layer diminishes in the shafts of the long bones. In this study, a simple ultrasonic in vivo method for determining the thickness of the cortical bone layer was applied, and the suitability of two different signal analysis techniques, i.e., envelope and cepstral methods, for measuring cortical thickness was compared. The values of cortical thickness, as determined with both techniques, showed high linear correlations (r ges 0.95) with the thickness values obtained from in vitro measurements with a caliper or in vivo measurements by peripheral quantitative CT (pQCT). No systematic errors that could be related to the cortical thickness were found. The in vivo accuracy of the measurements was 6.6% and 7.0% for the envelope and cepstral methods, respectively. Further, the in vivo precision for the envelope and cepstral methods was 0.26 mm and 0.28 mm, respectively. Although the results are similar for both of the techniques, the simplicity of the envelope method makes it more attractive for clinical applications. In conclusion, a simple ultrasound measurement provides an accurate estimate of the cortical bone thickness. The techniques investigated may have clinical potential for osteoporosis screening and therefore warrant more extensive clinical investigations with healthy and osteoporotic individuals.

Spatial variation of acoustic properties is related with mechanical properties of trabecular bone

In clinical applications, ultrasound parameters are measured as an average value over a region of interest (ROI) or as a value at a single measurement point. Due to natural adaptation to loading conditions, trabecular bone is structurally, compositionally and mechanically heterogeneous and anisotropic. Thus, spatial variation of ultrasound parameters within ROI may contain valuable information on the mechanical integrity of trabecular bone. However, this issue has not been thoroughly investigated. In the present study, we aimed at investigating the significance of the spatial variation of ultrasound parameters for the prediction of mechanical properties of human trabecular bone. For this aim, parametric maps of apparent integrated backscattering (AIB), integrated reflection coefficient (IRC), speed of sound (SOS), average attenuation (AA) and normalized broadband ultrasound attenuation (nBUA) were calculated for femoral and tibial bone cylinders (n = 19-20). Further, the effect of time window length on the AIB, variation of AIB within ROI and association between AIB and bone mechanical properties were characterized. Based on linear correlation analysis, spatial variation of AIB, assessed as standard deviation of measurements within ROI, was a strong predictor of bone ultimate strength (r = -0.82, n = 19, p < 0.01). Further, the time window length affected absolute values of AIB and strength of correlation between AIB and bone ultimate strength. Interestingly, linear combination of mean IRC and spatial variation of AIB within ROI was the strongest predictor of bone ultimate strength (r = 0.92, n = 19, p < 0.01). In conclusion, our findings suggest that the measurement of two-dimensional parametric maps of ultrasound parameters could yield information on bone status not extractable from single point measurements. This highlights the potential of parametric imaging in osteoporosis diagnostics.

Dual-frequency ultrasound technique minimizes errors induced by soft tissue in ultrasound bone densitometry

Background: Most bone ultrasound devices are designed for through-transmission measurements of the calcaneus. In principle, ultrasound backscattering measurements are possible at more typical fracture sites of the central skeleton. Unfortunately, soft tissue overlying the bones diminishes reliability of these measurements. Purpose: To apply the single-transducer dual-frequency ultrasound (DFUS) technique to eliminate the errors induced by soft tissue on the measurements of integrated reflection coefficient (IRC) in human distal femur in vivo. Material and Methods: Ultrasound and dual-energy X-ray absorptiometry (DXA) examinations were conducted on a bodybuilder during a 21-week training and dieting period. Results: Significant changes in quantity and composition of soft tissue took place during the diet. However, DXA measurements showed no significant effects on bone density measurements. The single transducer DFUS technique enabled the determination of local soft-tissue composition, as verified by comparison with the DXA (r=0.91, n=8, p<0.01). Further, the technique eliminated the soft-tissue-induced error from IRC measured for the bone. The uncorrected IRC associated significantly with the change in local soft-tissue composition (r=−0.83, n=8, p<0.05), whereas the corrected IRC values showed no significant dependence (r=−0.30, n=8, p=0.46) on local soft-tissue composition. Conclusion: The DFUS technique may significantly enhance the accuracy of clinical ultrasound measurements of bone.

Dual-Frequency Ultrasound—New Pulse–Echo Technique for Bone Densitometry

Quantitative ultrasound has been suggested for screening of osteoporosis. Most commercial ultrasound devices are based on the through-transmission measurement of calcaneus, which is not a typical fracture site. In contrast to through-transmission measurements, reflection and backscattering measurements may be conducted at typical fracture sites such as vertebra and proximal femur. At these regions, soft tissues overlying bones affect reliability of the measurements. In this study, a novel dual-frequency ultrasound (DFUS) pulse-echo technique is introduced for reduction of the errors induced by soft tissues. First, DFUS was validated using elastomer samples. For further validation, human trabecular bone samples (n = 25) covered with heterogeneous soft tissues were measured at frequencies of 2.25 MHz and 5.0 MHz. The DFUS technique reduced (p < 0.01) the mean error induced by soft tissue from 58.6% to -4.9% and from 127.4% to 23.8% in broadband ultrasound backscattering and integrated reflection coefficient (at 5.0 MHz), respectively. To conclude, the DFUS, being the first ultrasound technique capable of determination of the composition and thickness of the soft tissue overlying the bone, may enhance the accuracy of clinical ultrasound measurements. Thereby, DFUS shows a significant clinical potential.

Ultrasound Backscatter Measurements of Intact Human Proximal Femurs - Relationships of ultrasound parameters with tissue structure and mineral density.

Ultrasound reflection and backscatter parameters are related to the mechanical and structural properties of bone in vitro. However, the potential of ultrasound reflection and backscatter measurements has not been tested with intact human proximal femurs ex vivo. We hypothesize that ultrasound backscatter can be measured from intact femurs and that the measured backscattered signal is associated with cadaver age, bone mineral density (BMD) and trabecular bone microstructure. In this study, human femoral bones of 16 male cadavers (47.0±16.1 years, range: 21-77 years) were investigated using pulse-echo ultrasound measurements at the femoral neck in the antero-posterior direction and at the trochanter major in the anteroposterior and lateromedial directions. Recently introduced ultrasound backscatter parameters, independent of cortical thickness, e.g., time slope of apparent integrated backscatter (TSAB) and mean of the backscatter difference technique (MBD) were obtained and compared with the structural properties of trabecular bone samples, extracted from the locations of ultrasound measurements. Moreover, more conventional backscatter parameters, e.g., apparent integrated backscatter (AIB) and frequency slope of apparent integrated backscatter (FSAB) were analyzed. Bone mineral density of the intact femurs was evaluated using dual energy X-ray absorptiometry (DXA). AIB and MDB measured from the femoral neck correlated significantly (p<0.01) with the neck BMD (R2=0.44 and 0.45), cadaver age (R2=0.61 and 0.41) and several structural parameters, e.g., bone volume fraction (R2=0.33 and 0.39, p<0.05 and p<0.01), respectively. To conclude, ultrasound backscatter parameters, measured from intact proximal femurs, are significantly related (p<0.05) to structural properties and mineral density of trabecular bone.

New method for point-of-care osteoporosis screening and diagnostics

SummaryDue to the lack of diagnostics in primary health care, over 75xa0% of osteoporotic patients are not diagnosed. A new ultrasound method for primary health care is proposed. Results suggest applicability of ultrasound method for osteoporosis diagnostics at primary health care.IntroductionWe lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a new ultrasound (US) method is proposed for osteoporosis diagnostics.MethodsA total of 572 Caucasian women (age 20 to 91xa0years) were examined using pulse-echo US measurements in the tibia and radius. This method provides an estimate of bone mineral density (BMD), i.e. density index (DI). Areal BMD measurements at the femoral neck (BMDneck) and total hip (BMDtotal) were determined by using axial dual-energy X-ray absorptiometry (DXA) for women older than 50xa0years of age (nu2009=u2009445, ageu2009=u200968.8u2009±u20098.5xa0years). The osteoporosis thresholds for the DI were determined according to the International Society for Clinical Densitometry (ISCD). Finally, the FRAX questionnaire was completed by 425 participants.ResultsOsteoporosis was diagnosed in individuals with a T-score −2.5 or less in the total hip or femoral neck (nu2009=u200975). By using the ISCD approach for the DI, only 28.7xa0% of the subjects were found to require an additional DXA measurement. Our results suggest that combination of US measurement and FRAX in osteoporosis management pathways would decrease the number of DXA measurements to 16xa0% and the same treatment decisions would be reached at 85.4xa0% sensitivity and 78.5xa0% specificity levels.ConclusionsThe present results demonstrate a significant correlation between the ultrasound and DXA measurements at the proximal femur. The thresholds presented here with the application to current osteoporosis management pathways show promise for the technique to significantly decrease the amount of DXA referrals and increase diagnostic coverage; however, these results need to be confirmed in future studies.

Numerical analysis of uncertainties in dual frequency bone ultrasound technique

Quantitative ultrasound (QUS) measurements are used in the diagnostics of osteoporosis. However, the variation in the thickness and composition of the overlying soft tissue causes significant errors to the bone QUS parameters and diminishes the reliability of the technique in vivo. Recently, the dual frequency ultrasound (DFUS) technique was introduced to minimize the errors related to soft tissue effects. In this study, the significance of soft tissue induced errors and their elimination with the DFUS technique were simulated using the finite difference time domain technique. Furthermore, we investigated the potential of the DFUS corrected integrated reflection coefficient (IRC) of bone to detect changes in the cortical bone density. The effects of alterations in the thickness of fat and lean tissue layers and the inclination between the soft-tissues and between the soft tissue-bone layers were simulated. When the angle of the soft tissue interface was zero, i.e., perpendicular to the incident ultrasound beam, the DFUS-calculated soft tissue composition correlated highly linearly with the true soft tissue composition. The inclination between the soft tissue-bone layers was found to be critical. Even a 2-degree inclination between the soft tissue and the bone surface induced an almost 18% relative error in the corrected IRC. Increasing the inclination between the soft tissue layers increased the error in the DFUS-calculated lean and fat tissue thickness. This error was especially significant at inclination angles greater than 20 degrees. The significant soft tissue induced errors in IRC values (>300 %) could be effectively minimized (<10%) by means of the DFUS correction. Importantly, after the DFUS correction, physiologically relevant variation in the cortical bone density could be detected (p<0.05).

Technical and practical improvements in arthroscopic indentation technique for diagnostics of articular cartilage softening

Indentation measurements have been proposed to serve as sensitive in vivo diagnostics of cartilage degeneration. However, practical difficulties have hindered the use of quantitative indentation techniques during routine arthroscopies. In this study we modified the previously commercial indentation technique by designing software for quality control of manual indentations. With the modifications, our aim was to introduce more rapid and less erroneous measurements, as well as more automatic and objective analyses. The performance of the technique was tested in situ using six bovine medial tibial plateaus. All measurements were conducted by three operators. The intraoperator reproducibility was reasonable (CV%u200a=u200a7.1%) and the interoperator reproducibility was good (intraclass correlation coefficientu200a=u200a0.976). Further, the novel technique was tested by a single operator using 10 bovine medial tibial plateaus. The indentation stiffness values determined with the arthroscopic instrument correlated significantly with the dynamic (ru200a=u200a0.823) and equilibrium (ru200a=u200a0.752) moduli as well as tissue water (ru200a=u200a–0.830) and hydroxyproline (ru200a=u200a0.776) contents. To conclude, the novel measurement technique showed good reproducibility and was found to give valuable information on cartilage properties. Most importantly, the measurements and analyses were more straightforward and automatic than those introduced in the original indentation approach.