Bioimpedance-based measurement method for simultaneous acquisition of respiratory and cardiac gating signals.

Respiratory and cardiac motion artefacts impair the quality and reliability of medical imaging, particularly in nuclear medicine. At worst, the interpretation of distorted images may lead to inadequate or unnecessary treatment. Image artefacts can be minimized by gating the image acquisition according to respiratory phase and cardiac contractions. However, currently there are no clinically established dual-gating methods in nuclear medicine imaging. The aim of this study is to validate a previously determined optimized bioimpedance measurement configuration against traditional respiratory and cardiac measurement systems in 12 volunteers. High agreement and excellent correlations (r = 0.944-0.999) were found between respiratory peak-to-peak amplitudes as well as temporal respiratory and cardiac intervals. Above all, good quality respiratory and cardiac gating signals were obtained from all test subjects with a fairly regular sinus rhythm. Importantly, both signals were acquired simultaneously with a single device. Due to the simplicity of this inexpensive method, the technique has high potential to be adopted for dual-gating in clinical practice in the future.

Effect of bone marrow on acoustic properties of trabecular bone--3D finite difference modeling study.

The composition of bone marrow is influenced by many factors, such as age and diseases. The present numerical study investigates the contribution of marrow on the acoustic measurements of trabecular bone. Cylindrical bone samples (n = 11), extracted from three anatomical sites of human cadaver knees, were imaged with a high-resolution microtomography (microCT). Three-dimensional finite difference time domain (FDTD) models (Wave 3000 Pro 2.2, Cyberlogic Inc., NY, USA) were created using the segmented microCT images of each sample. First, we evaluated the effect of voxel size on the computer resource requirements, morphological parameters and acoustic simulations. Second, the effect of bone marrow on ultrasonic measurements was assessed. The simulations were repeated with two voxel sizes before and after substitution of bone marrow (i.e., fat) with water. The voxel size of the FDTD mesh controlled the fine structure of the modeled calcified matrix and significantly affected the simulation results. However, present simulations showed that the effect of bone marrow on ultrasound parameters can be reliably simulated with the applied voxel sizes of 72 and 90 microm. Ultrasound attenuation and speed were found (p < 0.01) to decrease and increase, respectively, when bone marrow was substituted with water. Moreover, reflection from the surface of the sample increased (p < 0.01) and backscatter from internal structures decreased (p < 0.01) after removal of marrow. The effect of bone marrow on the acoustic properties was stronger in samples with low bone volume fraction. The present results indicate that the amount and quality of bone marrow significantly influence the acoustic properties of trabecular bone. Possible interindividual differences in the composition of bone marrow may increase uncertainty in clinical ultrasound diagnostics of osteoporosis. Importantly, the effect is most significant in osteoporotic low-density 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 transmission technique as a potential tool for physical evaluation of monolithic matrix tablets.

The aim of this study was to investigate the effects of tablet porosity and particle size fraction of compacted Starch acetate powders, with and without model drug caffeine, on acoustic properties of tablets. The ultrasound velocity was determined from the transmission measurements. Tablets of starch acetate (SA DS 2.7) powder with two particle size fractions of 0-53 and 0-710 microm were compressed with a compaction simulator. Porosities of tablets varied in the range from 12% to 43% for both particle size fractions. Strong associations were found between the ultrasound velocity and physical properties of the tablets such as porosity and particle size fraction. Interestingly, ultrasound velocity was practically insensitive to inclusion of the model drug caffeine with the concentrations used. Based on this study ultrasound transmission method is a potential non-destructive tool for studying structural changes of tablets and other solid dosage forms.

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.

Acoustic properties of trabecular bone--relationships to tissue composition.

In osteoporosis, changes in tissue composition and structure reduce bone strength and expose it to fractures. The current primary diagnostic technique, i.e., dual energy X-ray absorptiometry, measures areal bone mineral density (BMD) but provides no direct information on trabecular structure or organic composition. Although still poorly characterized, ultrasound techniques may bring about information on bone composition and structure. In this study, relationships of 2.25-MHz ultrasound speed, attenuation, reflection and backscattering with composition of human trabecular bone (n=26) were characterized experimentally, as well as by using numerical analyses. We also determined composition of the trabecular sample (fat and water content, bone volume fraction) and that of the calcified matrix (mineral, proteoglycan and collagen content of trabeculae). In experimental analyses, bone volume fraction and mineral content of the calcified matrix were the only determinants of BMD. Further, bone volume fraction served as the strongest determinant of ultrasound parameters (r=0.51-0.87). In numerical simulations, density and mechanical properties of the calcified matrix systematically affected ultrasound speed, attenuation, reflection and backscattering. However, partial correlation coefficients revealed only low associations(|r|

Effect of human trabecular bone composition on its electrical properties.

Mechanical properties of bone are determined not only by bone mineral density (BMD), but also by tissue trabecular structure and organic composition. Impedance spectroscopy has shown potential to diagnose trabecular bone BMD and strength, however, the relationships between organic composition and electrical and dielectric properties have not been systematically investigated. To investigate these issues organic composition of 26 human trabecular bone samples harvested from the distal femur and proximal tibia was determined and compared with relative permittivity, loss factor, conductivity, phase angle, specific impedance and dissipation factor measured at wide range (50 Hz to 5 MHz) of frequencies. A strong linear correlation was found between the relative permittivity at 1.2 MHz and trabecular bone fat content (r = -0.85, p<0.01, n=26). On the other hand, relative permittivity measured at 200 Hz served as a good predictor of water content (r = 0.83). Phase angle, specific impedance and especially conductivity were strongly related to the trabecular bone dry density and water content (|r| > or = 0.69). Variation in bone tissue collagen content was strongly related to the relative permittivity measured at 1.2 MHz (r = 0.64), but only moderately to other parameters. Glycosaminoglycan content showed no significant relations with any investigated electrical parameters. The present study indicates that if the trabecular bone composition is known, the relationships presented in this study could facilitate calculation of current field distribution, e.g. during electrical stimulation of osteogenesis. On the other hand, our results suggest that permittivity measured at low (<1 kHz) or high (>100 kHz) frequencies could be used, e.g. during implant surgery, for prediction of trabecular bone water or fat contents, respectively.

Prediction of mechanical properties of trabecular bone using quantitative MRI.

Techniques for quantitative magnetic resonance imaging (MRI) have been developed for non-invasive estimation of the mineral density and structure of trabecular bone. The R*(2) relaxation rate (i.e. 1/T*(2)) is sensitive to bone mineral density (BMD) via susceptibility differences between trabeculae and bone marrow, and by binarizing MRI images, structural variables, such as apparent bone volume fraction, can be assessed. In the present study, trabecular bone samples of human patellae were investigated in vitro at 1.5 T to determine the ability of MRI-derived variables (R*(2) and bone volume fraction) to predict the mechanical properties (Young's modulus, yield stress and ultimate strength). Further, the MRI variables were correlated with reference measurements of volumetric BMD and bone area fraction as determined with a clinical pQCT system. The MRI variables correlated significantly (p < 0.01) with the mechanical variables (r = 0.32-0.46), BMD (r = 0.56) and bone structure (r = 0.51). A combination of R*(2) and MRI-derived bone volume fraction further improved the prediction of yield stress and ultimate strength. Although pQCT showed a trend towards better prediction of the mechanical properties, current results demonstrate the feasibility of combined MR imaging of marrow susceptibility and bone volume fraction in predicting the mechanical strength of trabecular bone and bone mineral density.

Interrelationships between electrical properties and microstructure of human trabecular bone.

Microstructural changes, such as reduction of trabecular thickness and number, are characteristic signs of osteoporosis leading to diminished bone strength. Electrical and dielectric parameters might provide diagnostically valuable information on trabecular bone microstructure not extractable from bone mineral density measurements. In this study, structural properties of human trabecular bone samples (n=26) harvested from the distal femur and proximal tibia were investigated using the computed microtomography (microCT) technique. Quantitative parameters, e.g. structural model index (SMI) or trabecular bone volume fraction (BV/TV), were calculated. In addition, the samples were examined electrically over a wide frequency range (50 Hz-5 MHz) using a two-electrode impedance spectroscopy set-up. Relative permittivity, loss factor, conductivity, phase angle, specific impedance and dissipation factor were determined. Significant linear correlations were obtained between the dissipation factor and BV/TV or SMI (|r| 0.70, p<0.01, n=26). Principal component analyses, conducted on electrical and structural parameters, revealed that the high frequency principal component of the dissipation factor was significantly related to SMI (r=0.72, p<0.01, n=26). The linear combination of high and low frequency relative permittivity predicted 73% of the variation in BV/TV. To conclude, electrical and dielectric parameters of trabecular bone, especially relative permittivity and dissipation factor, were significantly and specifically related to a trabecular microstructure as characterized with microCT. The data gathered in this study constitute a useful basis for theoretical and experimental work towards the development of impedance spectroscopy techniques for detection of bone quality in vitro or in special cases of open surgery.

Prediction of mechanical properties of human trabecular bone by electrical measurements.

In trabecular bone, the interrelationships of electrical and dielectric properties with mechanical characteristics are poorly known. Information on these relations is crucial for evaluation of the diagnostic potential of impedance techniques. In this study, electrical and dielectric properties, i.e. permittivity, conductivity, phase angle, loss factor, specific impedance and dissipation factor of human trabecular bone samples (n=26, harvested from the distal femur and proximal tibia) were characterized in a wide frequency range (50 Hz-5 MHz). Mechanical properties, i.e. Young's modulus, ultimate strength, yield stress, yield strain and resilience of the samples (n=20) were determined by using destructive compressive testing. Subsequently, measurements of electrical and dielectric properties were repeated after mechanical testing. The measurements were also repeated for the control samples (n=6) that were not mechanically tested. Electrical, dielectric or mechanical properties showed no significant differences between the intact femoral and tibial samples. The electrical and dielectric parameters as well as the linear correlations between the dielectric and electrical parameters with mechanical parameters were strongly frequency dependent. At the frequency of 1.2 MHz, the relative permittivity showed the strongest linear correlations with the Young's modulus (r=0.71, p<0.01, n=20) and ultimate strength (r=0.73, p<0.01, n=20). Permittivity and dissipation factor showed statistically significant changes after mechanical testing. Our results suggest that the measurements of low frequency electrical and dielectric properties may provide information on the mechanical status of trabecular bone and, possibly, may even help to diagnose bone microdamage. In the future, these measurement techniques may be further developed for use during open surgery, such as bone grafting or total hip replacement surgery.

Dual energy x-ray laser measurement of calcaneal bone mineral density.

In dual energy x-ray absorptiometry (DXA) the photon attenuation is assumed to be similar in soft tissue overlying, adjacent to and inside the measured bone. In the calcaneal dual energy x-ray laser (DXL) technique, this assumption is not needed as attenuation by soft tissues at the local bone site is determined by combining DXA and heel thickness measurements. In the present study, 38 subjects were measured with DXL Calscan, Lunar PIXI and Lunar DPX-IQ DXA instruments and Hologic Sahara ultrasound instrument, and the performance and agreement of the instruments were analysed. Furthermore, numerical simulations on the effect of non-uniform fat-to-lean tissue ratio within soft tissue in heel were conducted. In vivo short-term precision (CV%, sCV%) of DXL Calscan (1.24%, 1.48%) was similar to that of Lunar PIXI (1.28%, 1.60%). Calcaneal areal bone mineral densities (BMD, g cm(-2)) measured using DXL Calscan and Lunar PIXI predicted equally well variations in BMD of femoral neck (r2 = 0.63 and 0.52, respectively) or lumbar spine (r2 = 0.61 and 0.64, respectively), determined with Lunar DPX-IQ. BMD values measured with DXL Calscan were, on average, 19% lower (p < 0.01) than those determined with Lunar PIXI. Interestingly, the difference in BMD values between instruments increased as a function of body mass index (BMI) (r2 = 0.17, p < 0.02) or heel thickness (r2 = 0.37, p < 0.01). Numerical simulations suggested that the spatial variation of soft tissue composition in heel can induce incontrollable inaccuracy in BMD when measured with the DXA technique. Theoretically, in contrast to DXA instruments, elimination of the effect of non-uniform soft tissue is possible with DXL Calscan.

Electrical and dielectric properties of bovine trabecular bone--relationships with mechanical properties and mineral density.

Interrelationships of trabecular bone electrical and dielectric properties with mechanical characteristics and density are poorly known. While electrical stimulation is used for healing fractures, better understanding of these relations has clinical importance. Furthermore, earlier studies have suggested that bone electrical and dielectric properties depend on the bone density and could, therefore, be used to predict bone strength. To clarify these issues, volumetric bone mineral density (BMDvol), electrical and dielectric as well as mechanical properties were determined from 40 cylindrical plugs of bovine trabecular bone. Phase angle, relative permittivity, loss factor and conductivity of wet bovine trabecular bone were correlated with Young's modulus, yield stress, ultimate strength, resilience and BMDvol. The reproducibility of in vitro electrical and dielectric measurements was excellent (standardized coefficient of variation less than 1%, for all parameters), especially at frequencies higher than 1 kHz. Correlations of electrical and dielectric parameters with the bone mechanical properties or density were frequency-dependent. The relative permittivity showed the strongest linear correlations with mechanical parameters (r > 0.547, p < 0.01, n = 40, at 50 kHz) and with BMDvol (r = 0.866, p < 0.01, n = 40, at 50 kHz). In general, linear correlations between relative permittivity and mechanical properties or BMDvol were highest at frequencies over 6 kHz. In addition, a significant site-dependent variation of electrical and dielectric characteristics, mechanical properties and BMDvol was revealed in bovine femur (p < 0.05, Kruskall-Wallis H-test). Based on the present results, we conclude that the measurement of electrical and dielectric properties provides quantitative information that is related to bone quantity and quality.