Christopher F. Njeh

The role of ultrasound in the assessment of osteoporosis : A review

Osteoporosis is now being recognized as a “silent epidemic” and there is an increasing need to improve its diagnosis and management. Quantitative ultrasound (QUS) measurement [broadband ultrasound attenuation (BUA) and velocity] is emerging as an alternative to photon absorptiometry techniques in the assessment of osteoporosis. The fundamental principles governing ultrasound measurements are discussed, and some of the commercially available clinical systems are reviewed, particularly in relation to data acquisition methods. A review of the published in vivo and in vitro data is presented. The general consensus is that ultrasound seems to provide structural information in addition to density. The diagnostic sensitivity of ultrasound measurement of the calcaneus in the prediction of hip fracture has been shown by recent large prospective studies to be similar to hip bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) and superior to spine BMD. Ultrasound has also been shown to correlate better with the type of hip fracture (intertrochanteric or cervical) than BMD and to provide comparable diagnostic sensitivity to spine BMD in vertebral fractures. It has also been observed that combining the results of both ultrasound and DXA BMD significantly improved hip fracture prediction. Areas where further research is required are identified.

Is Quantitative Ultrasound Dependent on Bone Structure? A Reflection

Abstract: Trabecular bone plays a significant role in maintaining bone structural integrity. Its density is a significant determinant of bone strength and fracture risk, but there is still unexplained variance. It has been suggested that the ability to measure structural information will improve the estimation of bone strength and fracture risk. Quantitative ultrasound (QUS) is a mechanical wave that can be influenced by bone structure, in addition to bone mineral density (BMD). This article reviews the evidence in the literature supporting or refuting this assumption. Theoretically, the propagation of QUS is influenced by both structure and density of the medium. QUS measurement in vivo shows weak but significant association with axial BMD. However, the association becomes stronger when measured in vitro. Broadband ultrasound attenuation (BUA) exhibits a nonlinear relationship with density over a large density range. When cubes of cancellous bone are measured in the three orthogonal directions, both BUA and speed of sound (SOS) show significant anisotropy which mirrors mechanical anisotropy. QUS has also been shown to correlate significantly with structural parameters measured by histomorphometry. However, structure remains a significant predictor after adjustment for BMD mainly in bovine samples. Other studies using phantoms of bone samples have also demonstrated that QUS is dependent on structure. There is preliminary indication that fractal dimensions are significantly associated with QUS. The ultimate usefulness of structural dependence of QUS will be in its ability to improve bone strength estimation above and beyond density. There is ample evidence documenting the ability of QUS to predict bone strength in vitro. BMD is a significant predictor of bone strength and the additive value of structure in estimating bone strength is variable. Clinically, ultrasound of the calcaneus is measured in one direction (medio-lateral) and the structural variation in this direction may be limited. Nevertheless, QUS can provide useful additional information to that provided by axial BMD due in part to different precision and accuracy errors and to biological discordance. On the whole one could conclude that ultrasound attenuation is due to structural parameters and these variables are also dependent on density.

Comparison of six calcaneal quantitative ultrasound devices : Precision and hip fracture discrimination

Abstract: Quantitative ultrasound (QUS) is now accepted as a useful tool in the management of osteoporosis. There are a variety of QUS devices clinically available with a number of differences among them, including their coupling methods, parameter calculation algorithms and sites of measurement. This study evaluated the abilities of six calcaneal QUS devices to discriminate between normal and hip-fractured subjects compared with the established method of dual-energy X-ray absorptiometry (DXA). The short-term and mid-term precisions of these devices were also determined. Thirty-five women (mean age 74.5 ± 7.9 years) who had sustained a hip fracture within the past 3 years, and 35 age-matched controls (75.8 ± 5.6 years) were recruited. Ultrasound measurements were acquired using six ultrasound devices: three gel-coupled and three water-coupled devices. Bone mineral density was measured at the hip using DXA. Discrimination of fracture patients versus controls was assessed using logistic regression analysis (expressed as age- and BMI-adjusted odds ratios per standard deviation decrease with 95% confidence interval) and receiver operating characteristics (ROC) curve analysis. Measurement precision was standardized to the biological range (sCV). The sCV ranged from 3.14% to 5.5% for speed of sound (SOS) and from 2.45% to 6.01% for broadband ultrasound attenuation (BUA). The standardized medium-term precision ranged from 4.33% to 8.43% for SOS and from 2.77% to 6.91% for BUA. The pairwise Pearson correlation coefficients between different devices was highly significant (SOS, r= 0.79–0.93; BUA, r= 0.71–0.92). QUS variables correlated weakly, though significantly, with femoral BMD (SOS, r= 0.30–0.55; BUA, r= 0.35–0.61). The absolute BUA and SOS values varied among devices. The gel-coupled devices generally had a higher SOS than water-coupled devices. Bone mineral density (BMD) and BUA were weakly correlated with weight (r= 0.48–0.57 for BMD and r= 0.18–0.54 for BUA), whereas SOS was independent of weight. All the QUS devices gave similar, statistically significant hip fracture discrimination for both SOS and BUA measures. The odds ratios for SOS (2.1–2.8) and BUA (2.4–3.4) were comparable to those for femoral BMD (2.6–3.5), as were the area under the curve (SOS, 0.65–0.71; BUA, 0.62–0.71; BMD, 0.65–0.74) from ROC analysis. Within the limitation of the sample size all devices show similar diagnostic sensitivity.

Ultrasound velocity of trabecular cubes reflects mainly bone density and elasticity.

Abstract. Studies have indicated that quantitative ultrasound (QUS) variables may be influenced by the mechanical properties of bone which in turn are determined by bones material and structural properties. However, from these studies it is unclear what role density, elasticity, and structure play in determining velocity. Eighteen defatted, 12-mm cubic trabecular bone specimens were cut from cadaveric specimens. Amplitude-dependent speed of sound (SOS) using a single point QUS system was assessed in three orthogonal axes. Magnetic resonance images were obtained, from which measures of apparent trabeuclar structure were derived. The specimens were nondestructively tested in compression along three orthogonal axes defined by the sides of the cubes. The elastic modulus (in the three directions) and the strength (in one direction) were determined. Trabecular BMD was measured by quantitative computed tomography. SOS varied significantly with direction of measurement, with the highest value in the axial direction (axial:1715 m/s, sagittal: 1662 m/second, and coronal: 1676 m/s). SOS of each of the three axes was generally associated with the various mechanical (r = 0.30–0.87), density (r = 0.81–0.93), and bone structural variables (0.3–0.8). However, after adjusting the SOS correlations by density, only the correlation with elasticity remained significant in the coronal direction. BMD alone explained 88–93% of variance in SOS whereas in the multivariate model, BMD plus elasticity and/or anisotropic variables explained 96–98% of the variance in SOS. Variability of SOS is explained mostly by density and to a small extent by elasticity or anisotropy. Since only 2–6% of the variance of the QUS measurement is not explained by density and elasticity, one could conclude that the remaining variance reflects other properties of bone or perhaps simply measurement error. Evidence that these other properties may be structure related is only found in the anisotropy of QUS parameter.

Radiation exposure in bone mineral density assessment

Osteoporosis is a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue which leads to diminished biomechanical competence of the skeleton and low-trauma or atraumatic fractures. Due to increased awareness of the impact of osteoporosis on the elderly population, the use of bone densitometric techniques is becoming more widespread. Considerable progress has been made in the development of non-invasive methods for the assessment of the skeleton. While DXA and QCT are commonly used techniques, the popularity of other approaches such as RA, SXA and QUS is gaining grounds. QCT has an advantage over the other techniques in its ability to measure the true volumetric density of trabecular or cortical bone. We therefore present an overview of these current techniques for bone mineral density (BMD) measurements. In the second section we discuss the radiation doses incurred in BMD measurements by patients and methods for reducing patient and staff radiation exposure are given. Studies of radiation dose to patient from DXA confirms that patient dose is small (0.08-4.6 muSv) compared to that given by many other investigations involving ionizing radiation. Fan beam technology with increased resolution has resulted in increase patient dose radiation dose (6.7-31 muSv) but this is still relatively small. Carrying vertebral morphometry using DXA also incurs less radiation dose (< 60 muSv) than standard lateral radiographs QCT has radiation dose (25-360 muSv) comparable to simple radiological examination such as chest X-ray but lower than imaging CT. Radiation dose from other techniques such as RA and SXA are in the same order of magnitude as pencil beam DXA. For pencil beam DXA and SXA systems the time average dose to staff from scatter is very low even with the operator sitting as close as 1 m from the patient during measurement. However the scatter dose from fan beam DXA systems is considerable higher and approaches limits set by regulator bodies for occupational exposure.

Accelerated Partial Breast Irradiation (APBI): A review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.

An in vitro investigation of the dependence on sample thickness of the speed of sound along the specimen

To measure the speed of sound (SOS), most quantitative ultrasound (QUS) devices use the transmission mode, whereby two transducers are placed on opposite sides of the sample. This mode is limited to a few specific skeletal sites because of the varying configuration of bone geometry and varying amounts of overlying soft tissue at most other sites. The aim of this study was to address the dependence of SOS measured along the sample on the thickness and composition of the bone sample. Bovine samples from mid-femur and trochanter, and perspex phantoms were used. We prepared the perspex samples in the shapes of blocks and cylinders to investigate the effect of wall thickness on SOS. The thickness of the blocks was decreased in decrements of 1 mm; a 22 mm diameter hole was drilled through the cylindrical samples and the hole size was gradually increased. The second configuration was also used with the bovine samples. For each experimental set-up five SOS measurements were acquired, with the probe aligned along the sample and a mean value computed. All measurements were taken with castor oil as the coupling agent, and in the cylindrical cases, the oil was used to fill the tube. The measurement precision determined as the root mean square coefficient of variation (RMSCV) was determined to be 0.14% and 0.65% for perspex and bovine samples respectively. The measured SOS on the perspex phantom (2760+/-4 m/s) was within the published values for bulk velocity. It was observed that for both perspex and bovine samples the SOS was independent of sample wall thickness greater than the wavelength (2.2 mm, 2.7 mm and 3.5 mm for perspex, trochanter and mid-femur respectively). The SOS decreased with sample wall thickness smaller than the wavelength in concordance with theoretical predictions. The SOS values obtained for bovine samples reflected either totally cortical (mid-femur) or a composite of cortical and cancellous bone (trochanter).

Quantitative Ultrasound of the Tibia Depends on Both Cortical Density and Thickness

Abstract: This study investigated whether tibial speed of sound (SOS; SoundScan 2000, Myriad Ultrasound Systems, Israel) reflects not only bone mineral density (BMD) but also tibial cortical thickness, as assessed by dual-energy X-ray absorptiometry (DXA) and Quantitative CT (QCT) at a site-matched location. The secondary focus of the study was how tibial SOS compares with BMD at the spine and the hip, the most widely used locations for densitometry. Twenty-two young normal (N) and 23 postmenopausal women with spinal fractures (Fx) (mean (SD) age 35 (8) and 70 (5) years) underwent quantitative ultrasound (QUS) SOS measurement at the left tibial midshaft. From site-matched QCT scans (three 3-mm slices spaced along the QUS measurement region), BMD and cortical thickness were computed (QCT-cBMD, QCT-cTh). The cortex in the CT images was then subdivided into three concentric and equally spaced bands, and QCT-cBMD was computed separately for each band. DXA was performed at the mid-tibia (TIB BMD), at the spine (SPINE BMD) and the hip (total hip, HIP BMD). Correlation coefficients between parameters were determined with least-square linear fits. Intergroup differences were assessed by analysis of covariance, whose r2 value reflects the percentage variation in the data explained by group assignment. SOS correlated significantly with site-matched parameters (QCT-cBMD, QCT-cTh and TIB BMD, all r= 0.6, p < 0.001), SPINE BMD and HIP BMD (both r= 0.5, p < 0.001). Multiple regression with both QCT-cBMD and QCT-cTh against SOS yielded r= 0.7 with both parameters contributing significantly. For the cortex band subdivision, SOS correlated better with QCT-cBMD in the outermost band of the cortex (r= 0.67) than with the more central bands (r= 0.59 and r= 0.53). Group assignment could best explain SPINE BMD (r2= 0.62) and HIP BMD (r2= 0.51). SOS was comparable to TIB BMD (r2= 0.3 vs. r2= 0.35).: Our findings suggest that the tibial SOS measurement depends on both the thickness and density of the tibia, but is more strongly influenced by the density of the cortex near the surface than by its interior parts. The power of tibial ultrasound to discriminate between normal and fracture patients was less than that of spinal and femoral DXA BMD and comparable to site-matched DXA BMD.

Assessment of a new quantitative ultrasound calcaneus measurement: Precision and discrimination of hip fractures in elderly women compared with dual X-ray absorptiometry

Abstract: The incidence of osteoporotic hip fracture increases in postmenopausal women with low hip bone mineral density (BMD). Dual X-ray absorptiometry (DXA) is the most commonly used technique for the assessment of bone status and provides good measurement precision. However, DXA affords little information about bone architecture. Quantitative ultrasound (QUS) systems have been developed to evaluate bone status for assessment of fracture risk. Our study was designed to assess a new QUS system from Hologic, the Sahara; to compare it with a previous model, the Walker-Sonix UBA 575+; and to investigate whether it is able to discriminate between women with and without fracture. Using both ultrasound devices, the measurements were performed at the heels of 33 postmenopausal women who had recently sustained hip fracture. A control group of 35 age-matched postmenopausal women was recruited for comparison. The total, neck and trochanter femoral BMD values were assessed using DXA for both groups. QUS and DXA measurements were significantly lower in fractured patients (p<0.005) than in the control group. The short-term, mid-term and standardized short-term precisions were used to evaluate the reproducibility of the two QUS systems. The Sahara showed a better standardized coefficient of variation for broadband ultrasound attenuation (BUA) than did the UBA 575+ (p<0.001). The correlation of BUA and speed of sound (SOS) between the two QUS devices was highly significant, with an r value of 0.92 for BUA and 0.91 for SOS. However, the correlation between DXA and ultrasound parameters ranged from 0.28 to 0.44. We found that ultrasound measurements at the heel were significant discriminators of hip fractures with odds ratios (OR) ranging from 2.7 to 3.2. Even after adjusting the logistic regressions for total, neck or trochanter femoral BMD, QUS variables were still significant independent discriminators of hip fracture. The areas under the ROC curves of each ultrasound parameter ranged from 0.75 to 0.78, and compared very well with femoral neck BMD (p>0.05). In conclusion, our study indicated that the calcaneal QUS variables, as measured by the Sahara system can discriminate hip fracture patients equally as well as hip DXA.

Assessment of bone status using speed of sound at multiple anatomical sites

Studies in vitro and in vivo have shown that quantitative ultrasound (QUS) is a valid tool for the assessment of bone status. Current QUS methods using the transmission technique are limited to one peripheral bone site. A new system, Sunlight Omnisense (Omnisense, Sunlight Medical Ltd., Rehovot, Israel), measures speed of sound (SOS, in m/s) along the surface of the bone based on an axial transmission technique. The Omnisense can measure SOS at several anatomical sites. This study evaluated the SOS at different anatomical sites in a healthy population. A total of 334 adult women from three research centers in the USA and Canada with a mean (+/- SD) age of 48.8 (+/- 17.4) years were enrolled in this study. SOS was measured at the proximal third phalanx, distal one third radius, midshaft tibia, and fifth metatarsal. The mean SOS (+/- SD) values for the phalanx, radius, tibia and metatarsal were 3984 (+/- 221), 4087 (+/- 147), 3893 (+/- 150) and 3690 (+/- 246) m/s, respectively. Each anatomical site SOS was significantly different (p < 0.001) from that of the other sites. SOS at the different anatomical sites was modestly, but significantly, correlated (r = 0.31 to 0.56, p < 0.001). Similar correlation coefficients were obtained for the T scores. The mean T scores for subjects over the age of 60 years were -1.94, -2.01, -0.97 and -1.42 for the phalanx, radius, tibia and metatarsal, respectively. The age of peak SOS and the rate of change thereafter varied with anatomical site, implying that the prevalence of osteopenia and osteoporosis was site-dependent if only one T score cut-off point was used. Comparing individuals, 10% to 17% of patients had T scores that differed by more than a factor of 2 between sites. Weight and age were some of the contributing factors to this heterogeneity. The Omnisense provides an opportunity to assess bone status at different anatomical sites. Whether or not combining measurements from all these anatomical sites will improve osteoporosis management still needs to be determined.