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Factors Influencing the Speed of Sound Through the Proximal Phalanges
Journal of Clinical Densitometry, vol. 2, no. 3, 241–249, Fall 1999 © Copyright 1999 by Humana Press Inc. All rights of any nature whatsoever reserved. 0169-4194/99/2:241–249/$12.25
Original Article
Factors Influencing the Speed of Sound Through the Proximal Phalanges Christopher F. Njeh PHD, CPHYs, 1,2 Alexander Richards MSC,2 Chris M. Boivin MPHIL, 2 Didier Hans PHD,1 Thomas Fuerst PHD,1 and Harry K. Genant1 MD 1Osteoporosis
and Arthritis Research Group, UCSF, San Francisco, CA; 2Nuclear Medicine Department, Queen Elizabeth Hospital, Birmingham, UK
Abstract The amplitude-dependent speed of sound (AD-SOS) in the proximal phalanges is reported to be sensitive to osteoporotic changes. We investigated the influence of bone thickness and cortical thickness on AD-SOS. Phantoms made of Perspex were designed to simulate different bone width (11–16 mm) and cortical thickness (3–7.5 mm). The phantoms were designed with two opposing flat and cylindrical surfaces. The effect of cortical thickness was examined by drilling holes (simulating the medullary canal) of different diameters (1–7 mm) in the middle of the perspex cylinders. The effect of sample thickness was investigated on solid Perspex phantoms of varied lengths. The standardized precision errors of AD-SOS measurement in vivo and in vitro on volunteers and phantoms were 2.8 and 0.9%, respectively. AD-SOS was influenced by the bone width, cortical thickness, and location along the phalanx. A decrease in either cortical width or cortical thickness resulted in a decrease in AD-SOS. The effect is dependent on whether the contact surface is curved or flat. It is possible that a curved surface has a focusing effect on the wave through the porous core, whereas for a flat surface, the path of the waves might not pass through the center. When cortical thickness and bone width were expressed as a ratio, there was a linear relationship between this ratio and AD-SOS through the phantoms. ADSOS was independent of thickness for samples greater than 11 mm. Key Words:
Quantitative ultrasound; speed of sound; bone width; phantom; combined cortical thickness.
structural deterioration of bone tissue, with a consequent decrease in the mechanical competence of bone, leading to an increase in susceptibility to fracture (1). Osteoporosis is now recognized as a major worldwide public health problem, with a considerable financial burden. Although there are established techniques for the diagnosis of osteoporosis such as dual X-ray absorptiometry (DXA) and quantitative computed tomography (2,3), there is still need for improvement. The clinical end point of osteoporosis is fracture, and bone strength is an important determinant of fracture risk. The literature makes clear
Introduction Bone status assessment has many applications including metabolic bone diseases such as osteoporosis and arthritis. Osteoporosis is a systemic skeletal disease characterized by low bone mass and Received 11/13/98; Revised 03/26/99; Accepted 03/29/99. Address correspondence to Dr. Christopher F. Njeh, Osteoporosis and Arthritis Research Group, 350 Parnassus Avenue, Suite 908, Department of Radiology, University of California, San Francisco, CA 94117-1349. E-mail: [email protected]
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242 that bone mineral density (BMD) is a good predictor of bone strength, accounting for up to 80% of its variance (4). However, there is a general desire to improve prediction of bone strength. Bone strength is dependent on other parameters such as the architecture and geometry of the sample (5). It is thought that ultrasound might give some architectural information about the bone and thus improve prediction of strength. The fact that quantitative ultrasound (QUS) is nonionizing, relatively portable, and relatively less expensive than DXA has generated a growing interest in its potential applications (4,6). Clinical QUS devices became available in the late 1980s. Most measure speed of sound (SOS) and/or broadband ultrasound attenuation (BUA) at the calcaneus. Although based on similar principles, quantitative ultrasound (QUS) instruments from different manufacturers have significant differences, particularly in their calibration methods, measurement sites (mainly at calcaneus, phalanges, or tibia), analysis software, and scanner design (4,7). These devices also vary in precision, the mode of data acquisition (fixed single point or imaging), coupling (water or gel), velocity definition (bone velocity, time of flight, SOS), and transit time measurement (4,8,9). These differences, combined with the fact that no absolute standard exists for ultrasound measurement, cause the readings obtained on the different instruments to vary significantly. As a consequence, results are not directly comparable among technologically different QUS devices (10), and each system must be evaluated independently for clinical utility and precision. In addition to equipment drift, precision is also affected by external factors. For QUS measurements performed with a water-based machine, these factors have been identified to include heel positioning, water temperature, and immersion time (11). Using a novel approach, the DBM Sonic 1200 (IGEA, Carpi, Italy) measures amplitude-dependent SOS (AD-SOS) in the proximal phalanges. AD-SOS is reported to be more sensitive to osteoporotic changes than previous devices. AD-SOS could be affected by different factors that can affect the interpretation of data from cross-sectional or serial measurements. The objectives of this study were as follows:
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Njeh et al. • To determine the impact of bone width and cortical width on AD-SOS • To determine the impact of sample thickness on the accuracy of AD-SOS measurement • To determine the effect of variation on the location of measurement along the proximal phalanges on AD-SOS These factors were investigated using phantoms and volunteers.
Materials and Methods AD-SOS AD-SOS was measured using the DBM Sonic 1200 (IGEA), which uses a fixed-point transmission technique. Two 12-mm diameter, 1.25-MHz transducers are assembled on a high-precision caliper (±0.02 mm) that measures the distance between the probes (Fig. 1) (12). The probes are positioned on the mediolateral phalangeal surfaces using the phalanx head as a reference point. Coupling is achieved by using standard ultrasound gel. The time of flight is defined as the time from emitted pulse to received signal, which is above a predetermined amplitude value. When a normal bone is tested, the amplitude of the first signal received is above the predetermined threshold, but for osteoporotic bone, significant attenuation occurs and the amplitude of the first signal is not enough to trigger the reading. The velocity thus measured is amplitude related, hence AD-SOS. This enables differences in the SOS as measured in normal and in osteoporotic bone to be magnified. The probes are gently rotated until the best signal (defined in terms of number and the amplitude of the peaks) is recorded on the screen. Measurements are carried out on each of the four phalanges and the results are averaged.
Phalangeal Phantoms In a clinical environment, a phantom is designed to mimic the material properties of a natural tissue, with particular reference to the parameter to be measured. The requirements of a bone phantom for ultrasound are as follows: 1. Its material and ultrasonic properties must approach those of bone.
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Fig. 1.
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Schematic representation of the phantom measurement, also indicating the terminology used.
2. Air bubbles must be absent, because they are highly attenuating to ultrasound and will create anomalous results. 3. It should be durable and stable, and allow controlled variation in its properties. Perspex was chosen, even though its ultrasound velocity (2700 m/s) is about 22% lower than that reported for cortical bone (13), because it satisfied the last two conditions. Perspex also has welldocumented acoustic properties. Phantoms made of Perspex were designed based on data obtained from our patient database and were used to simulate different bone widths. The finger mean bone widths (including soft tissue) in the proximal phalangeal region for 120 subjects were 15.57 ± 0.11, 14.74 ± 0.11, 13.93 ± 0.12, and 13.19 ± 0.11 mm for the index, middle, ring, and small finger, respectively. The effect of cortical thickness was examined by drilling holes of different diameters in the middle of the Perspex cylinders (Fig. 2). The diameter of the holes varied from 1 to 7 mm and the width of the
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samples varied from 11 to 17 mm. Perspex blocks 18 mm high and 60 mm long but of varying widths (1.5–16 mm) were used to investigate the effect of uniform sample thickness on AD-SOS. Measurements were carried out with the phantom and probe submerged in a water bath. Five measurements were acquired for each configuration and a mean value was computed. One block of Perspex was measured for 20 d, from which the in vitro measurement precision was determined.
Volunteers Ten healthy volunteers were recruited from Birmingham physics and medical physics departments. Eight men and two women ranging in age from 22 to 29 yr gave oral consent to participate in the study. Four repeated measurements were acquired from each volunteer, with repositioning to determine the precision in vivo. The effect of the position of the transducer along the phalanges was also investigated on these volunteers. Only the index
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Fig. 2. Samples of phantoms used, illustrating phantoms with variable bone width (11–17 mm) and cortical thickness (3.25–6.25 mm) but constant hole diameter (4.5 mm).
and middle fingers were used, because the remaining phalanges were not long enough for three separate readings to be recorded. AD-SOS was measured through the fingers of both hands with the probes in the normal position (i.e., pushed against the distal condyles of the proximal phalanx). In addition, AD-SOS was measured with the probes positioned across the middle phalanx and then at the proximal end of the proximal phalanges. The length of each proximal phalanx was recorded. The locations of the three measurements, which were recorded as a distance along each phalanx from the distal head, were then normalized.
Analysis The terminology used in the report is shown in Fig. 1, where bone width refers to AD, cortical thickness to AB, medullary canal to BC, and combined cortical thickness to AB + CD. In some cases, both bone width and cortical thickness decreased, so a combined parameter called “cortical index” was computed. This was defined as the ratio of combined cortical thickness and bone width: Cortical index = (AB + CD)/AD = (AD – BC)/AD This ratio is supposed to be independent of bone size (14). A similar ratio has been used to quantify osteoporosis (15).
Results The precision errors of AD-SOS measurement in vivo and in vitro on volunteers and phantoms Journal of Clinical Densitometry
were 0.64 and 0.2%, respectively. The standardized precision defined as coefficient of variation (CV)/annual rate of change of AD-SOS was calculated to be 2.8 and 0.9%, respectively (0.23%/yr was used as the annual rate of change [16,17]). The AD-SOS measured on the phantoms ranged from 2400 to 2700 m/s, which was generally higher than clinically observed AD-SOS (1700–2200). For a uniform and homogeneous Perspex block, AD-SOS was independent of sample width for the range of finger width observed clinically in adults (11–17 mm). There was a gradual decrease in AD-SOS in samples with a width of <10 mm, and no values were recorded for sample widths of <4 mm (Fig. 3). Cortical thickness, simulated by drilling holes in the Perspex, ranged from 3 to 7.5 mm. The AD-SOS was dependent on both bone width and cortical thickness (Fig. 4). When the bone width and cortical thickness were expressed as a ratio (cortical index), a linear relationship was observed with AD-SOS through the phantoms. This cortical index has been used before as a means of monitoring osteoporosis (15). It can be seen from Fig. 5 that the behavior of AD-SOS as a function of the cortical index was influenced by whether the interface was curved or flat. For the curved surface, AD-SOS was highly linearly correlated to the cortical index (R2 = 0.97) (Fig. 5). However, a lower correlation was found for ADSOS through the flat surfaces (R2 = 0.82). It is possible that a curved surface has a focusing effect on the wave through the porous core, whereas for a flat
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Fig. 3.
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The effect of the width of a homogeneous sample transversed by ultrasound on the measured SOS (AD-SOS).
Fig. 4. The relationship between AD-SOS and cortical thickness for different bone widths. ◆, 16 mm; ■, 15 mm; ▲, 14 mm; ×, 13 mm.
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Fig. 5. curved.
Njeh et al.
The relationship between AD-SOS and cortical index (ratio of cortical thickness and bone width). ▲, flat; ×,
Fig. 6. The effect of the longitudinal probe location on the proximal phalanges on the measured SOS (AD-SOS). The horizontal line represents the mean of the pooled data. The center line in the diamonds is the mean for each population. The height of the diamonds represents the 95% confidence intervals for the means and widths are proportional to the size of each population.
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Factors Influencing AD-SOS surface, the path of the waves might not necessarily pass through the center. AD-SOS in the volunteers was dependent on the position of the probe along the proximal phalanges. The highest velocity was for the position closest to the head of the phalanx (Fig. 6). The mean values were 2146, 2111, and 2048 m/s for the distal, mid-, and proximal phalanges, respectively. These mean differences among the locations were found to be statistically significant (p = <0.01).
Discussion Precision The AD-SOS measurement precision (CV) reported here is comparable to the manufacturer’s quoted value of 0.5% and similar to the 0.4–0.8% reported by other researchers (16,18). The CV values are similar to those reported for SOS measured by other QUS instruments (4) and are also similar to those reported with BMD at the lumbar spine, but better than BMD at the femur (19). One of the weaknesses of the precision measurement was that it was carried out only on young volunteers, so we cannot indicate whether the precision reported here holds true for older subjects with poorer signals. However, Duboeuf et al. (16) reported similar precision for young and elderly volunteers. As expected, the precision for the phantom was better than for the volunteers since there were no repositioning errors.
Clinical Relevance of Phantom Study AD-SOS is measured in vivo at the distal metaphysis of the proximal phalanx of the last four fingers. In the metaphysis, both cortical and trabecular bone are present, although the region of interest interrogated by the DBM Sonic 1200 is mostly cortical bone. Both types of bone tissue have been reported to be sensitive to age-related bone resorption. Cortical bone usually becomes more porous with advancing age owing to intracortical resorption (20). In addition, the cortices of long bone become thinner because the rate of endosteal resorption exceeds the rate of formation of bone (20–22). Taken together, the age-related losses of cortical and cancellous bone substantially increase the fragility Journal of Clinical Densitometry
247 of bone. We were able to mimic the thinning of the cortical shell by increasing the diameter of the pores in the phantom. Hence, the results reported here are clinically relevant.
Effect of Cortical Thickness The range of cortical thickness investigated was 3–7.5 mm, which was higher than observed in vivo. On a group of cadaver hands, we recorded the cortical thickness in the range of 0.35–2.6 mm (mean = 1.6 mm) (unpublished data). Irrespective of this difference, this investigation shows that AD-SOS is affected by changes in cortical thickness (Fig. 4). It would be expected that SOS decreases when the medullary canal increases since the pores are then occupied by water (or marrow in vivo). Both the pores and the constituents of the sample influence the final SOS. We observed a decrease in AD-SOS with an increase in hole diameter (a decrease in cortical thickness). A 1-mm decrease resulted in a 35m/s (1.3%) decrease in AD-SOS for the curved surface. Considering the AD-SOS measurement precision on the phantom was 0.2%, this decrease was significant. The rate of change was dependent on the contact surface. As evident in Fig. 5, the gradient for a curved surface (501 m/s) was higher than for a flat surface (186 m/s). The curved surface is a closer mimic of the clinical situation. It has been suggested that the curved surface has a focusing effect on the wave, with the ultrasound pathway passing through the center. In a similar experiment, Cadossi and Cane (12) studied the effect of milling and drilling on the second phalanx of the pig. They observed a 265-m/s decrease with a 4.5-mm change in the medullary canal. They also observed that the signal that first reaches the receiving probe represents the part of the ultrasound energy that is transmitted through the center of the phalanx. One clinical implication of the results presented in Fig. 4 is that AD-SOS might be artificially elevated in subjects with small bone width and similar cortical thickness. For example, a 13-mm-wide bone with a 5-mm cortical thickness has about 2.4% higher AD-SOS than a bone 16 mm wide with a 5mm cortical thickness. One could anticipate that in a normal population, cortical thickness will be related to bone width, and hence the observed artificial elevation will not be apparent. But if the cortical thick-
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248 ness becomes reduced because of disease, this will result in a decrease in AD-SOS, as demonstrated in Fig. 4. We were unable to simulate intracortical resorption, which causes an increase in porosity. Reports in the literature have documented that SOS is inversely proportional to porosity (23,24). Therefore, the combined effect of endosteal and intracortical resorption probably should result in a greater change in ADSOS. Cross-sectional studies have reported a decrease of AD-SOS of approx 5 m/s/yr (16).
Effect of Sample Thickness on Accuracy of AD-SOS Theoretically, the speed of ultrasound should be independent of the dimensions of the sample. However, this is only true when the sample thickness is very large compared to the wavelength of sound propagation (25). At sample thicknesses close to the wavelength of ultrasound, a dispersion occurs and SOS decreases with decreasing sample thickness (26). The DBM Sonic 1200 uses a 1.25-MHz transducer, so for this experimental setup the wavelength would be in the range of 1.8–2.2 mm. However, we observed a decrease in SOS from a 10-mm sample. There was no SOS value for samples smaller than 4 mm (Fig. 3). The lack of signal after 4 mm is owing partially to the software design, which records 0 for measurements of SOS lower than that of soft tissue. This is intended to eliminate artifacts, since clinically one does not expect to record a true measurement lower than that of soft tissue.
Effect of Location on AD-SOS A detailed look at the phalanges will reveal changes in their composition from the distal to the proximal part. At the middle, it is mostly cortical bone with the condyles having a high proportion of cancellous bone. Since ultrasound velocity is different in cancellous bone compared to cortical bone, the changes in the composition will affect the velocity. It was observed in Fig. 6 that the SOS was highly dependent on the position of the probe along the phalanx. The differences in the position were also statistically significant (p = 0.005 distal-mid, p = 0.001 distal-proximal, and p = 0.005 mid-proximal). For good reproducibility, it is recommended that a rigid protocol for positioning should be adhered to.
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Njeh et al. One of the weaknesses of the present study is that the cortical thicknesses were larger than those observed clinically. The design of the phantom including two surfaces meant that there was a limit on how small the thickness of the curved surface could be. However, the results could be extrapolated to the clinical range. Also, in the present study we were unable to investigate the impact of soft tissue. This would be especially relevant for rheumatoid arthritis patients in whom swelling occurs along the affected joints. It has been reported, for the calcaneus, that swelling affects both the SOS and BUA measurements for patients with edema (27). The pathway of the ultrasound waves may affect the way they interact with the medium. It has been suggested that for bone with a medullary canal, there is a possibility of two sonic pathways: cortical wave and medullary wave (28). We were unable to identify these two types of waves in our present experimental settings.
Conclusion The results of our study showed that AD-SOS measurement precision was similar to that of other QUS systems. In addition, bone width and cortical thickness affected AD-SOS. Furthermore, AD-SOS was linearly dependent on the cortical index (ratio of the cortical thickness and bone width). For samples without holes, it was observed that AD-SOS was independent of thickness for the range of finger thickness observed clinically in adults (11–17 mm). Finally, the longitudinal placement of the transducers had a significant effect on AD-SOS.
Acknowledgment We would like to acknowledge the assistance of the medical physics department’s workshop (Birmingham University) in preparing the phantoms and all the volunteers for their time. We would also like to thank David Breazeale (UCSF) for editing the manuscript.
References 1. Anonymous. 1993 Consensus development conference: diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 94:646–650.
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Factors Influencing AD-SOS 2. Genant HK, Engelke K, Fuerst T, Glüer CC, Grampp S, Harris ST, Jergas M, Lang T, Lu Y, Majumdar S, Mathur A, Takada M, et al. 1996 Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res 11(6):707–730. 3. Grampp S, Jergas M, Lang P, Steiner E, Fuerst T, Glüer CC, Mathur A, Genant HK, et al. 1996 Quantitative CT assessment of the lumbar spine and radius in patients with osteoporosis. AJR Am J Roentgenol 167(1):133–140. 4. Njeh CF, Boivin CM, Langton CM. 1997 The role of ultrasound in the assessment of osteoporosis: a review. Osteoporos Int 7(1):7–22. 5. Kleerekoper M, Villanueva AR, Stanciu J, Rao DS, Parfitt AM. 1985 The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tissue Int 37(6):594–597. 6. Fuerst T, Glüer CC, Genant HK. 1995 Quantitative ultrasound. Eur J Radiol 20(3):188–92. 7. Hans D, Fuerst T, Duboeuf F. 1997 Quantitative ultrasound bone measurement. Eur Radiol 7(Suppl. 2):S43–S50. 8. Laugier P, Fournier B, Berger G. 1996 Ultrasound parametric imaging of the calcaneus: in vivo results with a new device. Calcif Tissue Int 58(5):326–331. 9. Nicholson PHF, Lowet G, Langton CM, Dequeker J, Van der Perre G. 1996 A comparison of time-domain and frequency-domain approaches to ultrasonic velocity measurement in trabecular bone. Phys Med Biol (UK) 41(11):2421–2435. 10. Glüer CC, Consensus Group. 1997 Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. J Bone Miner Res 12(8):1280–1288. 11. Evans WD, Jones EA, Owen GM. 1995 Factors affecting the in vivo precision of broad-band ultrasonic attenuation. Phys Med Biol 40(1):137–151. 12. Cadossi R, Cane V. 1996 Pathways of transmission of ultrasound energy through the distal metaphysis of the second phalanx of pigs: an in vitro study. Osteoporos Int 6(3):196–206. 13. Hodgskinson R, Njeh CF, Whitehead MA, Langton CM. 1996 The non-linear relationship between BUA and porosity in cancellous bone. Phys Med Biol (UK) 41(11):2411–2420.
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249 14. Colbert C, Bachtell RS. 1981 Radiographic Absorptiometry (Photodensitometry). In: Non-invasive Measurements of Bone Mass and Their Clinical Application Cohn SH, ed. CRC Press, West Palm Beach, FL, 51–84. 15. Havelka S, Bartunkova V, Streda A. 1993 Bone indexes and cortical thickness in assessing osteoporosis in rheumatic patients. Scand J Rheumatol 2:57–60. 16. Duboeuf F, Hans D, Schott AM, Giraud S, Delmas PD, Meunier PJ. 1996 Ultrasound velocity measured at the proximal phalanges: precision and age-related changes in normal females. Rev Rhum Engl Ed 63(6):427–434. 17. Alenfeld FE, Wuster C, Funck C, Pereira-Lima JF, Fritz T, Meeder PJ, Ziegler R. 1998 Ultrasound measurements at the proximal phalanges in healthy women and patients with hip fractures. Osteoporos Int 8(5):393–398. 18. Ventura V, Mauloni M, Mura M, Paltrinieri F, de Aloysio D. 1996 Ultrasound velocity changes at the proximal phalanxes of the hand in pre-, peri- and postmenopausal women. Osteoporos Int 6(5):368–375. 19. Lilley J, Walters BG, Heath DA, Drole Z. 1991 In vivo and in vitro precision for bone density measured by dual-energy X-ray absorption. Osteoporos Int 1(3):141–146. 20. Meema HE, Meema S, Oreopoulos DG. 1998 Periosteal resorption of finger phalanges: radial versus ulnar surfaces. J Can Assoc Radiol 29(3):175–178. 21. Keshawarz NM, Recker RR. 1984 Expansion of the medullary cavity at the expense of cortex in postmenopausal osteoporosis. Metab Bone Dis Relat Res 5(5):223–228. 22. Aguado F, Revilla M, Villa LF, Rico H. 1997 Cortical bone resorption in osteoporosis. Calcif Tissue Int 60(4):323–326. 23. Clarke AJ, Evans JA, Truscott JG, Milner R, Smith MA. 1994 A phantom for quantitative ultrasound of trabecular bone. Phys Med Biol (UK) 39(10):1677–1687. 24. Tavakoli MB, Evans JA. 1992 The effect of bone structure on ultrasonic attenuation and velocity. Ultrasonics 30(6):389–395. 25. Kolsky H. 1963 Stress waves in solid. Oxford: Clarendon Press.
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26. Ashman RB, Cowin SC, Van Buskirk WC, Rice JC. 1984 A continuous wave technique for the measurement of the elastic properties of cortical bone. J Biomech (UK) 17(5):349–361. 27. Johansen A, Stone MD. 1997 The effect of ankle oedema on bone ultrasound assessment at the heel. Osteoporos Int 7(1):44–47. 28. Langton CM, Riggs CM, Evans GP. 1991 Pathway of ultrasound waves in the equine third metacarpal bone. J Biomed Eng 13(2):113–118.
Journal of Clinical Densitometry
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Original Article
Factors Influencing the Speed of Sound Through the Proximal Phalanges Christopher F. Njeh PHD, CPHYs, 1,2 Alexander Richards MSC,2 Chris M. Boivin MPHIL, 2 Didier Hans PHD,1 Thomas Fuerst PHD,1 and Harry K. Genant1 MD 1Osteoporosis
and Arthritis Research Group, UCSF, San Francisco, CA; 2Nuclear Medicine Department, Queen Elizabeth Hospital, Birmingham, UK
Abstract The amplitude-dependent speed of sound (AD-SOS) in the proximal phalanges is reported to be sensitive to osteoporotic changes. We investigated the influence of bone thickness and cortical thickness on AD-SOS. Phantoms made of Perspex were designed to simulate different bone width (11–16 mm) and cortical thickness (3–7.5 mm). The phantoms were designed with two opposing flat and cylindrical surfaces. The effect of cortical thickness was examined by drilling holes (simulating the medullary canal) of different diameters (1–7 mm) in the middle of the perspex cylinders. The effect of sample thickness was investigated on solid Perspex phantoms of varied lengths. The standardized precision errors of AD-SOS measurement in vivo and in vitro on volunteers and phantoms were 2.8 and 0.9%, respectively. AD-SOS was influenced by the bone width, cortical thickness, and location along the phalanx. A decrease in either cortical width or cortical thickness resulted in a decrease in AD-SOS. The effect is dependent on whether the contact surface is curved or flat. It is possible that a curved surface has a focusing effect on the wave through the porous core, whereas for a flat surface, the path of the waves might not pass through the center. When cortical thickness and bone width were expressed as a ratio, there was a linear relationship between this ratio and AD-SOS through the phantoms. ADSOS was independent of thickness for samples greater than 11 mm. Key Words:
Quantitative ultrasound; speed of sound; bone width; phantom; combined cortical thickness.
structural deterioration of bone tissue, with a consequent decrease in the mechanical competence of bone, leading to an increase in susceptibility to fracture (1). Osteoporosis is now recognized as a major worldwide public health problem, with a considerable financial burden. Although there are established techniques for the diagnosis of osteoporosis such as dual X-ray absorptiometry (DXA) and quantitative computed tomography (2,3), there is still need for improvement. The clinical end point of osteoporosis is fracture, and bone strength is an important determinant of fracture risk. The literature makes clear
Introduction Bone status assessment has many applications including metabolic bone diseases such as osteoporosis and arthritis. Osteoporosis is a systemic skeletal disease characterized by low bone mass and Received 11/13/98; Revised 03/26/99; Accepted 03/29/99. Address correspondence to Dr. Christopher F. Njeh, Osteoporosis and Arthritis Research Group, 350 Parnassus Avenue, Suite 908, Department of Radiology, University of California, San Francisco, CA 94117-1349. E-mail: [email protected]
241
242 that bone mineral density (BMD) is a good predictor of bone strength, accounting for up to 80% of its variance (4). However, there is a general desire to improve prediction of bone strength. Bone strength is dependent on other parameters such as the architecture and geometry of the sample (5). It is thought that ultrasound might give some architectural information about the bone and thus improve prediction of strength. The fact that quantitative ultrasound (QUS) is nonionizing, relatively portable, and relatively less expensive than DXA has generated a growing interest in its potential applications (4,6). Clinical QUS devices became available in the late 1980s. Most measure speed of sound (SOS) and/or broadband ultrasound attenuation (BUA) at the calcaneus. Although based on similar principles, quantitative ultrasound (QUS) instruments from different manufacturers have significant differences, particularly in their calibration methods, measurement sites (mainly at calcaneus, phalanges, or tibia), analysis software, and scanner design (4,7). These devices also vary in precision, the mode of data acquisition (fixed single point or imaging), coupling (water or gel), velocity definition (bone velocity, time of flight, SOS), and transit time measurement (4,8,9). These differences, combined with the fact that no absolute standard exists for ultrasound measurement, cause the readings obtained on the different instruments to vary significantly. As a consequence, results are not directly comparable among technologically different QUS devices (10), and each system must be evaluated independently for clinical utility and precision. In addition to equipment drift, precision is also affected by external factors. For QUS measurements performed with a water-based machine, these factors have been identified to include heel positioning, water temperature, and immersion time (11). Using a novel approach, the DBM Sonic 1200 (IGEA, Carpi, Italy) measures amplitude-dependent SOS (AD-SOS) in the proximal phalanges. AD-SOS is reported to be more sensitive to osteoporotic changes than previous devices. AD-SOS could be affected by different factors that can affect the interpretation of data from cross-sectional or serial measurements. The objectives of this study were as follows:
Journal of Clinical Densitometry
Njeh et al. • To determine the impact of bone width and cortical width on AD-SOS • To determine the impact of sample thickness on the accuracy of AD-SOS measurement • To determine the effect of variation on the location of measurement along the proximal phalanges on AD-SOS These factors were investigated using phantoms and volunteers.
Materials and Methods AD-SOS AD-SOS was measured using the DBM Sonic 1200 (IGEA), which uses a fixed-point transmission technique. Two 12-mm diameter, 1.25-MHz transducers are assembled on a high-precision caliper (±0.02 mm) that measures the distance between the probes (Fig. 1) (12). The probes are positioned on the mediolateral phalangeal surfaces using the phalanx head as a reference point. Coupling is achieved by using standard ultrasound gel. The time of flight is defined as the time from emitted pulse to received signal, which is above a predetermined amplitude value. When a normal bone is tested, the amplitude of the first signal received is above the predetermined threshold, but for osteoporotic bone, significant attenuation occurs and the amplitude of the first signal is not enough to trigger the reading. The velocity thus measured is amplitude related, hence AD-SOS. This enables differences in the SOS as measured in normal and in osteoporotic bone to be magnified. The probes are gently rotated until the best signal (defined in terms of number and the amplitude of the peaks) is recorded on the screen. Measurements are carried out on each of the four phalanges and the results are averaged.
Phalangeal Phantoms In a clinical environment, a phantom is designed to mimic the material properties of a natural tissue, with particular reference to the parameter to be measured. The requirements of a bone phantom for ultrasound are as follows: 1. Its material and ultrasonic properties must approach those of bone.
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Fig. 1.
243
Schematic representation of the phantom measurement, also indicating the terminology used.
2. Air bubbles must be absent, because they are highly attenuating to ultrasound and will create anomalous results. 3. It should be durable and stable, and allow controlled variation in its properties. Perspex was chosen, even though its ultrasound velocity (2700 m/s) is about 22% lower than that reported for cortical bone (13), because it satisfied the last two conditions. Perspex also has welldocumented acoustic properties. Phantoms made of Perspex were designed based on data obtained from our patient database and were used to simulate different bone widths. The finger mean bone widths (including soft tissue) in the proximal phalangeal region for 120 subjects were 15.57 ± 0.11, 14.74 ± 0.11, 13.93 ± 0.12, and 13.19 ± 0.11 mm for the index, middle, ring, and small finger, respectively. The effect of cortical thickness was examined by drilling holes of different diameters in the middle of the Perspex cylinders (Fig. 2). The diameter of the holes varied from 1 to 7 mm and the width of the
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samples varied from 11 to 17 mm. Perspex blocks 18 mm high and 60 mm long but of varying widths (1.5–16 mm) were used to investigate the effect of uniform sample thickness on AD-SOS. Measurements were carried out with the phantom and probe submerged in a water bath. Five measurements were acquired for each configuration and a mean value was computed. One block of Perspex was measured for 20 d, from which the in vitro measurement precision was determined.
Volunteers Ten healthy volunteers were recruited from Birmingham physics and medical physics departments. Eight men and two women ranging in age from 22 to 29 yr gave oral consent to participate in the study. Four repeated measurements were acquired from each volunteer, with repositioning to determine the precision in vivo. The effect of the position of the transducer along the phalanges was also investigated on these volunteers. Only the index
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Fig. 2. Samples of phantoms used, illustrating phantoms with variable bone width (11–17 mm) and cortical thickness (3.25–6.25 mm) but constant hole diameter (4.5 mm).
and middle fingers were used, because the remaining phalanges were not long enough for three separate readings to be recorded. AD-SOS was measured through the fingers of both hands with the probes in the normal position (i.e., pushed against the distal condyles of the proximal phalanx). In addition, AD-SOS was measured with the probes positioned across the middle phalanx and then at the proximal end of the proximal phalanges. The length of each proximal phalanx was recorded. The locations of the three measurements, which were recorded as a distance along each phalanx from the distal head, were then normalized.
Analysis The terminology used in the report is shown in Fig. 1, where bone width refers to AD, cortical thickness to AB, medullary canal to BC, and combined cortical thickness to AB + CD. In some cases, both bone width and cortical thickness decreased, so a combined parameter called “cortical index” was computed. This was defined as the ratio of combined cortical thickness and bone width: Cortical index = (AB + CD)/AD = (AD – BC)/AD This ratio is supposed to be independent of bone size (14). A similar ratio has been used to quantify osteoporosis (15).
Results The precision errors of AD-SOS measurement in vivo and in vitro on volunteers and phantoms Journal of Clinical Densitometry
were 0.64 and 0.2%, respectively. The standardized precision defined as coefficient of variation (CV)/annual rate of change of AD-SOS was calculated to be 2.8 and 0.9%, respectively (0.23%/yr was used as the annual rate of change [16,17]). The AD-SOS measured on the phantoms ranged from 2400 to 2700 m/s, which was generally higher than clinically observed AD-SOS (1700–2200). For a uniform and homogeneous Perspex block, AD-SOS was independent of sample width for the range of finger width observed clinically in adults (11–17 mm). There was a gradual decrease in AD-SOS in samples with a width of <10 mm, and no values were recorded for sample widths of <4 mm (Fig. 3). Cortical thickness, simulated by drilling holes in the Perspex, ranged from 3 to 7.5 mm. The AD-SOS was dependent on both bone width and cortical thickness (Fig. 4). When the bone width and cortical thickness were expressed as a ratio (cortical index), a linear relationship was observed with AD-SOS through the phantoms. This cortical index has been used before as a means of monitoring osteoporosis (15). It can be seen from Fig. 5 that the behavior of AD-SOS as a function of the cortical index was influenced by whether the interface was curved or flat. For the curved surface, AD-SOS was highly linearly correlated to the cortical index (R2 = 0.97) (Fig. 5). However, a lower correlation was found for ADSOS through the flat surfaces (R2 = 0.82). It is possible that a curved surface has a focusing effect on the wave through the porous core, whereas for a flat
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Fig. 3.
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The effect of the width of a homogeneous sample transversed by ultrasound on the measured SOS (AD-SOS).
Fig. 4. The relationship between AD-SOS and cortical thickness for different bone widths. ◆, 16 mm; ■, 15 mm; ▲, 14 mm; ×, 13 mm.
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Fig. 5. curved.
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The relationship between AD-SOS and cortical index (ratio of cortical thickness and bone width). ▲, flat; ×,
Fig. 6. The effect of the longitudinal probe location on the proximal phalanges on the measured SOS (AD-SOS). The horizontal line represents the mean of the pooled data. The center line in the diamonds is the mean for each population. The height of the diamonds represents the 95% confidence intervals for the means and widths are proportional to the size of each population.
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Factors Influencing AD-SOS surface, the path of the waves might not necessarily pass through the center. AD-SOS in the volunteers was dependent on the position of the probe along the proximal phalanges. The highest velocity was for the position closest to the head of the phalanx (Fig. 6). The mean values were 2146, 2111, and 2048 m/s for the distal, mid-, and proximal phalanges, respectively. These mean differences among the locations were found to be statistically significant (p = <0.01).
Discussion Precision The AD-SOS measurement precision (CV) reported here is comparable to the manufacturer’s quoted value of 0.5% and similar to the 0.4–0.8% reported by other researchers (16,18). The CV values are similar to those reported for SOS measured by other QUS instruments (4) and are also similar to those reported with BMD at the lumbar spine, but better than BMD at the femur (19). One of the weaknesses of the precision measurement was that it was carried out only on young volunteers, so we cannot indicate whether the precision reported here holds true for older subjects with poorer signals. However, Duboeuf et al. (16) reported similar precision for young and elderly volunteers. As expected, the precision for the phantom was better than for the volunteers since there were no repositioning errors.
Clinical Relevance of Phantom Study AD-SOS is measured in vivo at the distal metaphysis of the proximal phalanx of the last four fingers. In the metaphysis, both cortical and trabecular bone are present, although the region of interest interrogated by the DBM Sonic 1200 is mostly cortical bone. Both types of bone tissue have been reported to be sensitive to age-related bone resorption. Cortical bone usually becomes more porous with advancing age owing to intracortical resorption (20). In addition, the cortices of long bone become thinner because the rate of endosteal resorption exceeds the rate of formation of bone (20–22). Taken together, the age-related losses of cortical and cancellous bone substantially increase the fragility Journal of Clinical Densitometry
247 of bone. We were able to mimic the thinning of the cortical shell by increasing the diameter of the pores in the phantom. Hence, the results reported here are clinically relevant.
Effect of Cortical Thickness The range of cortical thickness investigated was 3–7.5 mm, which was higher than observed in vivo. On a group of cadaver hands, we recorded the cortical thickness in the range of 0.35–2.6 mm (mean = 1.6 mm) (unpublished data). Irrespective of this difference, this investigation shows that AD-SOS is affected by changes in cortical thickness (Fig. 4). It would be expected that SOS decreases when the medullary canal increases since the pores are then occupied by water (or marrow in vivo). Both the pores and the constituents of the sample influence the final SOS. We observed a decrease in AD-SOS with an increase in hole diameter (a decrease in cortical thickness). A 1-mm decrease resulted in a 35m/s (1.3%) decrease in AD-SOS for the curved surface. Considering the AD-SOS measurement precision on the phantom was 0.2%, this decrease was significant. The rate of change was dependent on the contact surface. As evident in Fig. 5, the gradient for a curved surface (501 m/s) was higher than for a flat surface (186 m/s). The curved surface is a closer mimic of the clinical situation. It has been suggested that the curved surface has a focusing effect on the wave, with the ultrasound pathway passing through the center. In a similar experiment, Cadossi and Cane (12) studied the effect of milling and drilling on the second phalanx of the pig. They observed a 265-m/s decrease with a 4.5-mm change in the medullary canal. They also observed that the signal that first reaches the receiving probe represents the part of the ultrasound energy that is transmitted through the center of the phalanx. One clinical implication of the results presented in Fig. 4 is that AD-SOS might be artificially elevated in subjects with small bone width and similar cortical thickness. For example, a 13-mm-wide bone with a 5-mm cortical thickness has about 2.4% higher AD-SOS than a bone 16 mm wide with a 5mm cortical thickness. One could anticipate that in a normal population, cortical thickness will be related to bone width, and hence the observed artificial elevation will not be apparent. But if the cortical thick-
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248 ness becomes reduced because of disease, this will result in a decrease in AD-SOS, as demonstrated in Fig. 4. We were unable to simulate intracortical resorption, which causes an increase in porosity. Reports in the literature have documented that SOS is inversely proportional to porosity (23,24). Therefore, the combined effect of endosteal and intracortical resorption probably should result in a greater change in ADSOS. Cross-sectional studies have reported a decrease of AD-SOS of approx 5 m/s/yr (16).
Effect of Sample Thickness on Accuracy of AD-SOS Theoretically, the speed of ultrasound should be independent of the dimensions of the sample. However, this is only true when the sample thickness is very large compared to the wavelength of sound propagation (25). At sample thicknesses close to the wavelength of ultrasound, a dispersion occurs and SOS decreases with decreasing sample thickness (26). The DBM Sonic 1200 uses a 1.25-MHz transducer, so for this experimental setup the wavelength would be in the range of 1.8–2.2 mm. However, we observed a decrease in SOS from a 10-mm sample. There was no SOS value for samples smaller than 4 mm (Fig. 3). The lack of signal after 4 mm is owing partially to the software design, which records 0 for measurements of SOS lower than that of soft tissue. This is intended to eliminate artifacts, since clinically one does not expect to record a true measurement lower than that of soft tissue.
Effect of Location on AD-SOS A detailed look at the phalanges will reveal changes in their composition from the distal to the proximal part. At the middle, it is mostly cortical bone with the condyles having a high proportion of cancellous bone. Since ultrasound velocity is different in cancellous bone compared to cortical bone, the changes in the composition will affect the velocity. It was observed in Fig. 6 that the SOS was highly dependent on the position of the probe along the phalanx. The differences in the position were also statistically significant (p = 0.005 distal-mid, p = 0.001 distal-proximal, and p = 0.005 mid-proximal). For good reproducibility, it is recommended that a rigid protocol for positioning should be adhered to.
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Njeh et al. One of the weaknesses of the present study is that the cortical thicknesses were larger than those observed clinically. The design of the phantom including two surfaces meant that there was a limit on how small the thickness of the curved surface could be. However, the results could be extrapolated to the clinical range. Also, in the present study we were unable to investigate the impact of soft tissue. This would be especially relevant for rheumatoid arthritis patients in whom swelling occurs along the affected joints. It has been reported, for the calcaneus, that swelling affects both the SOS and BUA measurements for patients with edema (27). The pathway of the ultrasound waves may affect the way they interact with the medium. It has been suggested that for bone with a medullary canal, there is a possibility of two sonic pathways: cortical wave and medullary wave (28). We were unable to identify these two types of waves in our present experimental settings.
Conclusion The results of our study showed that AD-SOS measurement precision was similar to that of other QUS systems. In addition, bone width and cortical thickness affected AD-SOS. Furthermore, AD-SOS was linearly dependent on the cortical index (ratio of the cortical thickness and bone width). For samples without holes, it was observed that AD-SOS was independent of thickness for the range of finger thickness observed clinically in adults (11–17 mm). Finally, the longitudinal placement of the transducers had a significant effect on AD-SOS.
Acknowledgment We would like to acknowledge the assistance of the medical physics department’s workshop (Birmingham University) in preparing the phantoms and all the volunteers for their time. We would also like to thank David Breazeale (UCSF) for editing the manuscript.
References 1. Anonymous. 1993 Consensus development conference: diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 94:646–650.
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Factors Influencing AD-SOS 2. Genant HK, Engelke K, Fuerst T, Glüer CC, Grampp S, Harris ST, Jergas M, Lang T, Lu Y, Majumdar S, Mathur A, Takada M, et al. 1996 Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res 11(6):707–730. 3. Grampp S, Jergas M, Lang P, Steiner E, Fuerst T, Glüer CC, Mathur A, Genant HK, et al. 1996 Quantitative CT assessment of the lumbar spine and radius in patients with osteoporosis. AJR Am J Roentgenol 167(1):133–140. 4. Njeh CF, Boivin CM, Langton CM. 1997 The role of ultrasound in the assessment of osteoporosis: a review. Osteoporos Int 7(1):7–22. 5. Kleerekoper M, Villanueva AR, Stanciu J, Rao DS, Parfitt AM. 1985 The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tissue Int 37(6):594–597. 6. Fuerst T, Glüer CC, Genant HK. 1995 Quantitative ultrasound. Eur J Radiol 20(3):188–92. 7. Hans D, Fuerst T, Duboeuf F. 1997 Quantitative ultrasound bone measurement. Eur Radiol 7(Suppl. 2):S43–S50. 8. Laugier P, Fournier B, Berger G. 1996 Ultrasound parametric imaging of the calcaneus: in vivo results with a new device. Calcif Tissue Int 58(5):326–331. 9. Nicholson PHF, Lowet G, Langton CM, Dequeker J, Van der Perre G. 1996 A comparison of time-domain and frequency-domain approaches to ultrasonic velocity measurement in trabecular bone. Phys Med Biol (UK) 41(11):2421–2435. 10. Glüer CC, Consensus Group. 1997 Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. J Bone Miner Res 12(8):1280–1288. 11. Evans WD, Jones EA, Owen GM. 1995 Factors affecting the in vivo precision of broad-band ultrasonic attenuation. Phys Med Biol 40(1):137–151. 12. Cadossi R, Cane V. 1996 Pathways of transmission of ultrasound energy through the distal metaphysis of the second phalanx of pigs: an in vitro study. Osteoporos Int 6(3):196–206. 13. Hodgskinson R, Njeh CF, Whitehead MA, Langton CM. 1996 The non-linear relationship between BUA and porosity in cancellous bone. Phys Med Biol (UK) 41(11):2411–2420.
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249 14. Colbert C, Bachtell RS. 1981 Radiographic Absorptiometry (Photodensitometry). In: Non-invasive Measurements of Bone Mass and Their Clinical Application Cohn SH, ed. CRC Press, West Palm Beach, FL, 51–84. 15. Havelka S, Bartunkova V, Streda A. 1993 Bone indexes and cortical thickness in assessing osteoporosis in rheumatic patients. Scand J Rheumatol 2:57–60. 16. Duboeuf F, Hans D, Schott AM, Giraud S, Delmas PD, Meunier PJ. 1996 Ultrasound velocity measured at the proximal phalanges: precision and age-related changes in normal females. Rev Rhum Engl Ed 63(6):427–434. 17. Alenfeld FE, Wuster C, Funck C, Pereira-Lima JF, Fritz T, Meeder PJ, Ziegler R. 1998 Ultrasound measurements at the proximal phalanges in healthy women and patients with hip fractures. Osteoporos Int 8(5):393–398. 18. Ventura V, Mauloni M, Mura M, Paltrinieri F, de Aloysio D. 1996 Ultrasound velocity changes at the proximal phalanxes of the hand in pre-, peri- and postmenopausal women. Osteoporos Int 6(5):368–375. 19. Lilley J, Walters BG, Heath DA, Drole Z. 1991 In vivo and in vitro precision for bone density measured by dual-energy X-ray absorption. Osteoporos Int 1(3):141–146. 20. Meema HE, Meema S, Oreopoulos DG. 1998 Periosteal resorption of finger phalanges: radial versus ulnar surfaces. J Can Assoc Radiol 29(3):175–178. 21. Keshawarz NM, Recker RR. 1984 Expansion of the medullary cavity at the expense of cortex in postmenopausal osteoporosis. Metab Bone Dis Relat Res 5(5):223–228. 22. Aguado F, Revilla M, Villa LF, Rico H. 1997 Cortical bone resorption in osteoporosis. Calcif Tissue Int 60(4):323–326. 23. Clarke AJ, Evans JA, Truscott JG, Milner R, Smith MA. 1994 A phantom for quantitative ultrasound of trabecular bone. Phys Med Biol (UK) 39(10):1677–1687. 24. Tavakoli MB, Evans JA. 1992 The effect of bone structure on ultrasonic attenuation and velocity. Ultrasonics 30(6):389–395. 25. Kolsky H. 1963 Stress waves in solid. Oxford: Clarendon Press.
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26. Ashman RB, Cowin SC, Van Buskirk WC, Rice JC. 1984 A continuous wave technique for the measurement of the elastic properties of cortical bone. J Biomech (UK) 17(5):349–361. 27. Johansen A, Stone MD. 1997 The effect of ankle oedema on bone ultrasound assessment at the heel. Osteoporos Int 7(1):44–47. 28. Langton CM, Riggs CM, Evans GP. 1991 Pathway of ultrasound waves in the equine third metacarpal bone. J Biomed Eng 13(2):113–118.
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