Appropriateness of internal digital phantoms for monitoring the stability of the UBIS 5000 quantitative ultrasound device in clinical trials

In bone status assessment, proper quality assurance/quality control is crucial since changes due to disease or therapeutic treatment are very small, in the order of 2–5%. Unlike for dual X-ray absorptiometry, quality control procedures have not been extensively developed and validated for quantitative ultrasound technology, limiting its use in longitudinal monitoring. While the challenge of developing an ideal anthropometric phantom is still open, some manufacturers use the concept of the internal digital phantom mimicking human characteristics to check the stability of their device. The objective of the study was to develop a sensitive model of quality control suitable for the correction of QUS patient data. In order to achieve this goal, we simulated a longitudinal device lifetime with both correct and malfunctioning behaviors. Then, we verified the efficiency of digital phantoms in detecting those changes and subsequently established the in vitro/in vivo relationship. This is the first time that an attempt to validate an internal digital phantom has made, and that this type of validation approach is used. The digital phantom (DP) was designed to mimic normal bone (BUAP2) and osteoporotic bone (BUAP1) properties. The DP was studied using the UBIS 5000 ultrasound device (DMS, France). Diverse malfunctions of the UBIS-5000 were simulated. Several series of measurements were performed on both BUAP1 and 2 and on 12 volunteers at each grade of malfunction. The effect of each simulated malfunction on in vivo and in vitro results was presented graphically by plotting the average BUA values against the percentage change from baseline. The change from baseline in BUA was modeled using linear regression, and the in vivo/in vitro ratio was obtained from the model. All experimentations influenced the measure of BUAP1 and 2 as well as the measure of our 12 volunteers. However, the degree of significance varied as a function of the severity of the malfunction, and the results also differed substantially in magnitude between in vivo and in vitro. Indeed, the DP was about 10 times more sensitive to variations of the transfer function than was the in vivo measurement, which is very reassuring. The sensitivity of the digital phantoms was reliable in the determination of simulated malfunctions of the UBIS-5000. The digital phantoms provided an accurate evaluation of the acoustic performance of the scanner, including the fidelity of transducers. In light of these results, the QC approach of the UBIS-5000 will be extremely simple to implement compared with other devices. Indeed, since the digital phantom was automatically measured during every patient measurement, the QC approach could be built on an individual level basis rather than on an average basis.     

Longitudinal precision of dual-energy x-ray absorptiometry in a multicenter study. The Nafarelin/Bone Study Group

Reproducibility is a key issue in both clinical and research applications of bone mineral density (BMD) measurements. To examine the longitudinal precision of dual-energy x-ray absorptiometry (DEXA) for the measurement of mineral density in vivo and in vitro, the performance of a group of instruments in the course of a multicenter longitudinal clinical trial was monitored. Measures were performed on eight identical machines (Hologic QDR1000) and analyzed using the same automated software program. Short-term precision was good in vitro, [anthropomorphic spine phantoms; mean intrasite coefficient of variation (CV) 0.42 +/- 0.1% (SD)] and in vivo (lumbar spine; CV 1.1 +/- 0.5%). Intersite measures of a single spine phantom (specified mineral content -57.8 g) revealed a range of 57.3-58.4 g (CV 0.7%). In two subjects intersite CV in vivo were 3.7 and 2.1% (spine) and 1.8 and 3.2% (femoral neck). At five sites frequent phantom measures were performed over a 1 year period (mean number of measures 196) and revealed a mean all-point CV of 0.43% (range 0.35-0.53%). Longitudinal precision in vivo was somewhat less (mean CV of spinal measures 1.1%, femoral neck 1.2%, trochanter 1.3%, and Ward's area 2.4%). At one additional site large variations in phantom measures heralded repeated mechanical failures that eventually required machine replacement. In summary, DEXA demonstrates good in vitro and in vivo longitudinal precision, providing the basis for expanded clinical and research usefulness. Nevertheless, stringent quality assurance measures are required to detect and respond to system malfunctions.     

Precision of quantitative ultrasound: comparison of three commercial scanners

Quantitative ultrasound (QUS) measurements of bone have been shown to be independent predictors of osteoporotic fracture risk. Drawbacks of this technique have included the precision of the scanners, which is said to be poorer than in dual-energy X-ray absorptiometry (DXA), in part due to difficulty in repositioning of the foot in an os calcis system and difficulty in comparison across different technologies. A new type of QUS scanner has been introduced that produces an image of the area scanned and is believed to improve precision by aiding repositioning. In this study, we compare three scanners: a dry system (McCue CUBA Clinical); a nonimaging water-bath system (Lunar Achilles(+)); and an imaging water-bath system (Osteometer DTU-One). Short-term phantom precision was calculated by repeating measurements ten times in succession on the manufacturer-supplied phantom. Long-term phantom precision was calculated by examining the phantom measurements over a 6 month period. In vivo precision was calculated in 26 normal volunteers (19 women, 7 men) and 20 women with osteoporosis. Monitoring time intervals (MTIs) were also calculated using the manufacturer's normative database. The MTI is the period between scans required to show that a "true" change has occurred, and was between 0.5 year for stiffness (a derived index produced by the Lunar Achilles instrument) and >5 years for all other measurements. The imaging system did not seem to improve precision. Precision for the QUS phantom was similar to that of DXA with a coefficient of variation (CV) of around 1.5% for BUA and <1% for speed of sound (SOS). The precision was such that the technique may be considered for monitoring skeletal changes. However, the change of bone mass at the os calcis in response to treatment was slow, which made the time needed to wait before assessing change, on the whole, longer than that for DXA. An exception may be the Lunar Achilles "stiffness" parameter, but this can only be determined in a longitudinal, comparative treatment study.     

Precision of Quantitative Ultrasound Measurement of the Heel Bone and Effects of Ambient Temperature on the Parameters

The goal of this study was to determine the magnitude of measurement error of a quantitative ultrasound (QUS) measurement system of the heel bone in a practical setting and to examine the effects of ambient temperature in the test room on QUS parameters. We assessed the intratest, intertest and interdevice coefficients of variation (CVs) for speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness in vitro using phantoms and in vivo using volunteers. The intratest CV was the smallest and the interdevice CV was the greatest for every QUS parameter. The intertest CVs in vivo were 0.50% for SOS, 2.53% for BUA and 4.38% for stiffness. The standardized precision error (sPE) of stiffness, however, was smaller than those of the other two parameters. The intertest sPEs in vivo of the QUS parameters were 2–3 times greater than that of the spine bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA). Using an average of duplicate measurements for the representative value of a subject could improve sPE of the QUS parameters to around 2 times greater than that of spine BMD. We examined five phantoms each with the QUS system under the ambient temperature conditions of 10, 20 and 30 °C. The lower the room temperature, the greater the values of all the QUS parameters obtained. We then assessed the effect of the season on the QUS parameters in healthy five women. SOS and stiffness were significantly greater in February (room temperature, 12.6 °C) than in June (22.4 °C) by 0.74% and 3.2% of overall means, respectively, by 10.1% and 4.3% as a standardized difference, or by 0.422 and 0.214 in Z-scores. This difference was likely to be caused by the difference in heel temperature between the seasons. The precision of the QUS system was inferior to that of conventional DXA densitometry. We recommend that institutions using several QUS system devices throughout the year at various locations monitor the precision of each device, make duplicate measurements for a single subject, use the same device for each patient being followed, and control the heel temperature of subjects by keeping the test room temperature constant throughout the year. Received: 15 October 1998 / Accepted: 19 May 1999     

Precision of dual-energy x-ray absorptiometry: Development of quality control rules and their application in longitudinal studies

In research settings, longitudinal measurements of bone mineral density have become an integral part of the assessment of patients with metabolic skeletal disorders. To adequately utilize longitudinal measures, confidence in the long-term precision of the measurement technique must be very high. Dual-energy x-ray absorptiometry (DXA) has become commonly utilized in this context, and to better understand its long-term precision and to develop quality assurance protocols for its use, we examined the performance of eight DXA machines over a 3 year period. Anthropomorphic spine phantoms were measured frequently on each machine during the period of observation, and precision was estimated from the consistency of these determinations. Overall precision was excellent (mean longitudinal coefficient of variation, 0.4%). Nevertheless, by using a series of objective quality control criteria, small alterations in the performance of each machine were identified (mean number of changes, 4.6 in 3 years; mean magnitude, 0.0039 g/cm², or 0.4%). The cumulative effects of those changes were sufficient to cause a significant (albeit minor) change in the regression slopes (phantom mineral density versus time) of most machines. The same quality control rules were also used to quantitate the magnitude of change and to adjust retrospectively machine performance during the period of observation, such that alterations were minimal and regression slopes were not significantly different from zero. Although the precision of DXA is excellent, alterations in machine function must be anticipated during longitudinal use. The development of quality control protocols provides the means to detect change objectively and to adjust for alterations in performance during the course of longitudinal evaluations.     

The effect of room temperature on dual-energy X-ray absorptiometry

There has been little published data on the effects of temperature on the performance of dual-energy X-ray absorptiometry (DXA) machines. We examined the effect of changes in ambient room temperature on the performance of three DXA scanners (DPXL, Expert-XL and Prodigy). The study involved repeat measurements of bone mineral density (BMD) using three different spine phantoms scanned at different ambient room temperatures, both before and after calibration procedures. The calibration or quality assurance (QA) scan calibrates the scanner, adjusting for the ambient room temperature at the time of calibration. There was a moderate correlation between change in temperature and change in BMD measured prior to recalibration for the Expert-XL ( r=0.58) during normal clinical scanning conditions. There was no observed change in phantom BMD with change in temperature measured using the DXPL or Prodigy. After temperature change, without repeat calibration measurements, there was a strong correlation between temperature change and change in BMD measured using the Expert-XL ( r=0.96, p<0.001). From the regression equation, a change of 2.5 degrees C could alter the calculated BMD result measured by the Expert-XL by 1.5%, which would significantly affect the precision of the DXA system. There was no significant correlation between temperature and BMD in the DXPL or Prodigy. The observed differences between the densitometers and the effect of temperature change are most likely due to the differing types of detector systems used. Operators must be made aware that solid state detectors of the sort used in the Expert-XL (charge-coupled devices, CCDs) are significantly affected by changes in ambient room temperature.     

A Comparison of Phantoms for Cross-Calibration of Lumbar Spine DXA

The aim of this project was to compare three phantoms used for cross-calibration of dual-energy X-ray absorptiometers with an in vivo cross-calibration. The phantoms used were the Bona Fide Phantom (BFP), the European Spine Phantom (ESP) and the GE Lunar Aluminum Spine Phantom (ASP). The cross calibration was for L2–L4 lumbar spine bone mineral density (BMD) on a GE Lunar DPX-L and Hologic QDR 2000. The in vivo cross-calibration was obtained using 72 subjects (61 female, 11 male; mean age 49 years, range 14–84 years). The phantoms were measured 10 times without repositioning on both instruments. A further, long-term cross-calibration was obtained with the BFP over a 9 month period. The true linear relationship between the two instruments was calculated used a standardized principal components method. The mean residuals were calculated between each phantom cross-calibration line and the in vivo data to obtain a measure of the goodness of fit between the phantom cross-calibration and the in vivo data. There was no significant difference between the in vitro and in vivo cross-calibrations. The long-term BFP cross-calibration gave an in vitro cross-calibration that is closest to the in vivo cross-calibration in this group of subjects. When calculating Hologic QDR BMD from results on the GE Lunar DPX-L, the ASP underestimates Hologic QDR 2000 BMD by 4% at high BMD and overestimates by 4% at low BMD. The ESP cross-calibration overestimates Hologic QDR2000 BMD by 1% at high BMD and 4% at low BMD. The BFP performs best, overestimating Hologic QDR2000 BMD by between 1.2% and 1.8%, whilst the difference between the long-term BFP cross-calibration and the in vivo data is less than 1% over the range of BMD covered. Received: 19 October 2001 / Accepted: 9 July 2002     

Reproducibility of Fan-Beam DXA Measurements in Adults and Phantoms

As part of a multicenter study, we examined the intersite reproducibility of bone mineral content (BMC) and areal density (BMD) among three fan-beam dual-energy X-ray absorptiometry (DXA) instruments from one manufacturer, all using the same software version. Spine, femur, and body-composition phantoms were each scanned nine times at each center. Over a 3-wk period, the same 10 adults were scanned once at each of the three centers. For the spine and femur phantoms, the precision errors were 0.3-0.7%. For the body-composition phantom, the precision errors were 0.8-2.8%. The intersite coefficients of variation for the human measurements varied from 1.1 to 6.8%, depending on the bone site. We conclude that even when using the same fan-beam DXA model and software, an intersite cross-comparison using only phantoms may be inadequate. Comparisons based solely on the use of a spine phantom are insufficient to ensure compatibility of human bone mineral data at other bone sites or for the whole body.     

Performance of a dedicated light delivery and dosimetry device for photodynamic therapy of nasopharyngeal carcinoma: phantom and volunteer experiments

The objective of this study was to develop a light delivery and measurement device for photodynamic therapy (PDT) in the nasopharyngeal cavity, which achieves a homogeneous and reproducible fluence rate distribution to a target area and provides proper shielding of predefined risk areas.MATERIALS AND METHODS: A flexible silicone applicator was developed, incorporating light delivery and dosimetry fibers. The applicator can be inserted through the mouth and fixed in the nasopharyngeal cavity. Tissue optical phantoms were prepared on the basis of optical properties measured in vivo using diffuse reflectance spectroscopy (DRS). The fluence rate over the length of the applicator surface was measured in air, in tissue optical phantoms and in five healthy volunteers. RESULTS: The fluence rate distribution over the applicator surface in air and tissue optical phantom was found to be more homogeneous (SD/mean 3.8% and 18.3%, respectively) than the fluence rate distribution in five volunteers (SD/mean ranging from 19% up to 52%). The maximum observed fluence rate build-up in the nasopharynx varied between subjects and ranged from a factor of 4.1-6.9. Shielding of the risk area such as the soft palate and tongue was effective. CONCLUSIONS: In air and in tissue optical phantoms the fluence rate distribution of the device was highly homogeneous. The observed inter-subject and intra-subject variations in fluence rate in healthy volunteers originated from differences in optical properties and nasopharyngeal geometry. Light delivery based on a single tissue surface measurement will not be adequate. In situ dosimetric measurements are required to determine the light fluence delivered to a geometrically complex site such as the nasopharynx. These observations should be taken in consideration when developing light applicators for PDT of the nasopharynx and other non-uniform surfaces.     

Ultrasound measurements on os calcis: Precision and age-related changes in a normal female population

We performed ultrasound measurements in the calcaneus of 512 healthy women. Broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were obtained with a Lunar Achilles ultrasonic instrument. Subjects studied were one group of 67 women working in our hospital (group A) and two groups which are part of two large prospective cohort studies (groups B and C). Group B consisted of 244 women aged 31–79 years randomly selected from a large insurance company, and group C consisted of 201 women aged 74–91 years randomly selected from the electoral rolls. Dual-energy X-ray absorptiometry (DXA) measurements of femoral neck and total body were performed with a Hologic QDR 2000 for group B and with a Lunar DPX Plus for group C. The in vitro precision of the Achilles, estimated by measuring a phantom daily for 45 days, was 0.84% for BUA and 0.12% for SOS. We assessed the in vivo short-term precision in 20 healthy volunteers working at the hospital, measured three times each. The coefficients of variation were 0.93% (±0.21) for BUA and 0.15% (±0.03) for SOS. The precision error was compared with the true variation, to obtain a standardized coefficient of variation. We analysed the three groups pooled together (n=512) and found for BUA an average 20% decrease and for SOS a 5% decrease between the ages of 20 and 90 years. We also performed separate analyses of subjects younger than 50 and older than 50 years, and within each 10-year age group we found that BUA was stable or slightly increased from 20 to 50 years and then decreased after 50. In contrast, SOS did not increase but decreased from the age of 20. We compared DXA measurements of the femoral neck and the total body with ultrasound measurements in groups B and C. In both groups the correlations were better with total body DXA than with femoral neck and spine DXA.     

Which bone densitometry and which skeletal site are clinically useful for monitoring bone mass?

Long-term precision, as well as reproducibility, is important for monitoring bone mineral density (BMD) alteration in response to aging or therapy. In order to investigate which bone densitometry and which skeletal site are clinically useful for monitoring bone mass, we examined the standardized long-term precision of several bone density measurements in 83 healthy Japanese women. Annual BMD measurements were performed for 5 or 6 years using dual X-ray absorptiometry (DXA) on the lumbar spine, radius (EXP5000) and calcaneus (HeelScan); peripheral quantitative computed tomography (pQCT) on the radius (Densiscan1000); and quantitative ultrasound (QUS) on the calcaneus (Achilles+). The long-term precision error for the individual subject was given by the standard error of estimate (SEE), and the standardized long-term precision was defined as the percentage coefficient of variation (CV%) divided by the percentage ratio of the annual bone-loss rate. Based on the CV% of spinal DXA, speed of sound (SOS) and diaphyseal pQCT showed significantly higher precision than others, while radial ultradistal (UD) DXA and heel DXA showed significantly lower precision. The long-term precision errors of other measurements were statistically the same as that of the spinal DXA. The spinal DXA, the radial DXA, and pQCT at both the distal metaphysis and diaphysis showed high rates of annual bone loss. The radial trabecular BMD (pQCT) was significantly higher than that of spinal DXA. The annual rates of bone loss of QUS and of heel DXA were significantly lower than that of spinal DXA. Taken together, standardized long-term precision was obtained in the spinal DXA and radial pQCT. In conclusion, spinal DXA and radial pQCT were considered the most useful monitoring method for osteoporosis, while QUS was considered less useful.     

Switching from DXA pencil-beam to fan-beam. I: Studies in vitro at four centers

The performance of the Hologic QDR-2000 DXA osteodensitometer was critically evaluated at four centers, using at all four centers one bone equivalent humanoid spine phantom supplied by the manufacturer. Results were compared with results from Hologic QDR-1000/W using that phantom tested at the same centers.

It appears that the concept of fan-beam scanning—as used in the QDR-2000: a fan-beam, a linear array detector above the phantom, and an x-ray tube located rather close to the spine below the phantom—creates problems due to the magnification effect of the fan beam. The effect of decreasing the distance between the “vertebrae” of the phantom and the couch are: bone mineral content (BMC) increases by 2.8% per cm, projected area (Area) by 2.8% per cm, and bone mineral density (BMD) is unchanged.

When QDR-1000/W is upgraded to QDR-2000, BMD is relatively constant, but there are shifts of BMC and Area which are partly due to the magnification effect of the fanbeam. Replacement of a QDR-1000/W with a QDR-2000 can invalidate longitudinal measurements, even for BMD, unless the proportionality factors of the QDR-2000 are checked and, if necessary, changed. This is true for switching from QDR-1000/W to pencil-beam mode of QDR-2000 or to fanbeam mode of QDR-2000.

Even with pencil-beam mode, the long-term precision error with phantoms is higher for QDR-2000 than for QDR-1000/W (for BMD, 0.47% versus 0.35%).     

Precision and accuracy of joint space width measurements of the medial compartment of the knee using standardized MTP semi-flexed radiographs

OBJECTIVE: To quantify the precision and accuracy of measurements of joint space width (JSW) and joint space narrowing (JSN) from the medial tibiofemoral compartment of knee radiographs using a simple and easily adaptable protocol. METHODS: Radiographs of a caliper (a surrogate for JSW) were obtained to determine the precision limits of the system under ideal conditions. Bilateral knee radiographs from 10 healthy volunteers were obtained at three different times using the metatarsophalangeal (MTP) semi-flexed view posterior-anterior position without fluoroscopy. A backlit digitizing tablet and three manual methods were used to measure JSW and analyses of precision were performed. The accuracy of measuring change in JSW (a measure of JSN) was estimated from radiographs of cadaver knees that were placed in a servo-hydraulic device that moved the femur relative to the tibia through known intervals. RESULTS: Radiographic measurements of the caliper inter-blade distance were comparable to the resolution limits of the backlit digitizing tablet (0.025 mm). Repeated radiography of healthy subject knees produced JSW standard deviation (SD) measurements of 0.08 mm by the median SD method, and 0.11 mm by repeated measures analysis. The accuracy of JSN measurements in the cadaver knees as a mean difference from the known reference value was 0.09 mm. CONCLUSION: The results indicate a high level of precision in measurements of JSW from MTP semi-flexed view knee radiographs of normal volunteers. Reproducibility was attained through careful subject positioning without fluoroscopy and the use of a backlit digitizing tablet. From the cadaver study we can predict that greater than 0.13 mm of measured JSN represents actual or true change in JSN. This radiographic technique can be used as a primary measure for early knee osteoarthritis (OA) when cartilage thickness is decreasing and limited bony remodeling has occurred.     

Inaccuracies inherent in patient-specific dual-energy X-ray absorptiometry bone mineral density measurements: comprehensive phantom-based evaluation.

An extensive series of dual-energy X-ray absorptiometry (DXA) scans and dual polyenergetic X-ray simulation studies of 150 different phantom arrays were carried out to evaluate quantitatively the extent of systematic inaccuracies inherent in DXA in vivo bone mineral density (BMD). These measurements are particularly relevant to lumbar vertebral and proximal femoral sites. The phantoms were specially fabricated near perfect absorptiometric representations of bone material, red marrow (RM) and yellow marrow (YM), and extraosseous mixtures of fat (F) and lean muscle that spanned the full range of soft tissue anthropometrics encountered clinically. In each case, the DXA-measured BMD values obtained using Hologic, Lunar, and Norland densitometers were found to be virtually the same and to be in excellent agreement with the corresponding quantitative simulation study BMD results. Comparisons of the known phantom BMD values and DXA-measured BMD in each case allowed the BMD inaccuracies to be evaluated. These present findings show that these ubiquitous inaccuracies in DXA BMD methodology are of in vivo soft tissue anthropometric genesis. It is found that patient-specific DXA-measured in vivo BMD inaccuracies as high as 20% or more can be readily anticipated clinically, particularly in cases of osteopenic, osteoporotic, and elderly patients. As these inaccuracies exceed considerably DXA precision errors, they may compromise patient-specific evaluations of fracture risk and, in prospective studies, mask or exaggerate clinically significant true changes in BMD. It is concluded that the magnitudes and variability of inherent inaccuracies in DXA-measured in vivo BMD underscore the need for prudence and circumspection in interpretations and assessments of DXA-based clinical studies.     

Changes in QUS and BMD Measurements with Antiresorptive Therapy: A Two-Year Longitudinal Study

There is lack of consensus on whether quantitative ultrasound (QUS) measurements can be used to monitor response to therapy. The aim of this 2-year longitudinal study was to assess whether calcaneal QUS measurement variables respond to antiresorptive therapy and whether these measurements display adequate long-term precision to be useful for monitoring purposes. The study population consisted of 195 postmenopausal women divided into three groups: Group 1: 39 women treated with antiresorptive therapy who commenced treatment at baseline; Group 2: 25 women treated with antiresorptive therapy who had been on treatment for at least 2 years at baseline; Group 3: 131 women who did not taken estrogen, bisphosphonates, or calcium during the 2-year study period. Subjects had baseline and 12 and 24 months follow-up BMD measurements at the lumbar spine (LS), femoral neck (FN), and total hip (THIP) and calcaneal QUS measurements of broadband ultrasound attenuation (BUA) and speed of sound (SOS). BUA and SOS were combined to provide an estimate of heel BMD (Est heel BMD). For women in Group 1, all BMD and QUS measurement variables increased significantly from baseline after 2 years of treatment. For women in Group 2, only THIP BMD and BUA increased significantly after 2 years and the changes were less than those observed in Group 1 women. The overall treatment effect for each measurement variable, defined as the difference in the mean absolute changes between Groups I and 3 after 2 years, was 0.08, 0.03, and 0.04 g/cm2 for LS, FN, and THIP BMD, and for BUA, SOS, and Est heel BMD it was 5.8 dB/MHz, 13.1 m/sec, and 0.05 g/cm2, respectively. When the overall treatment effect was expressed in T-score units, the effect was greatest for LS BMD (0.65 T-score units) and lowest for FN BMD (0.31 T-score units). QUS measurement variables yielded intermediate values of 0.43- 0.52 T-score units. The average least significant change (LSC) was 0.38 T-score units for BMD measurements, whereas the LSC for QUS measurements was three times greater at approximately 1.20 T-score units. Ninety-four percent of the women in Group 1 showed changes in LS BMD that exceeded the LSC after two years, while the percentage was lower for the other measurement variables ranging from approximately 6% for FN BMD, SOS and Est heel BMD to 50% for THIP BMD. A lower percentage of women in Groups 2 and 3 displayed changes that exceeded the LSC for both BMD and QUS measurement variables. Changes in all QUS variables were significantly correlated with changes in LS BMD, with correlation coefficients ranging from 0.26 to 0.40. In conclusion, calcaneal QUS measurement variables were found to show a highly significant response to antiresorptive therapy. However, the precision of QUS measurements was not good enough to allow QUS to be used for monitoring response to treatment. Future improvements in the precision of calcaneal QUS measurements are required to increase the utility of QUS for monitoring purposes.     

Measurement of human trabecular bone by novel ultrasonic bone densitometry based on fast and slow waves

Summary  Two longitudinal transmitted waves, fast and slow waves, were observed by employing a new quantitative ultrasound (QUS) method. The trabecular bone measurements generated by this method reflect three-dimensional structural information, and the new QUS parameters were able to identify vertebral fractures. Introduction  The aims were to identify new quantitative ultrasound (QUS) parameters that based on new QUS method reflecting not only bone volume but also the microstructures of trabecular bone ex vivo and to observe how much they predict fracture risk in vivo. Methods   Ex vivo measurement: Three human femoral heads were used for the experiment. Attenuation of the slow wave, attenuation of the fast wave, speed of the slow wave, speed of the fast wave (SOFW), bone mass density of trabecular bone, and elastic modulus of the trabecular bone (EMTb) of each specimen were obtained using a new QUS method and compared with three-dimensional structural parameters measured by micro-computed tomography. In vivo measurement: Eighty-nine volunteers were enrolled, and the bone status in the distal radius was measured using a new QUS method. These parameters were compared with data evaluated by peripheral quantitative computed tomography and dual X-ray absorptiometry. Results   Ex vivo measurement: SOFW and EMTb showed correlations with the parameter of trabecular anisotropy. In vivo measurement: The new QUS parameters were able to identify vertebral fractures. Conclusion  The newly developed QUS technique reflects the three-dimensional structure and is a promising method to evaluate fracture risk.     

Long-term and resegmentation precision of quantitative cartilage MR imaging (qMRI)

OBJECTIVE: Follow up of osteoarthritis (OA) and evaluation of structure modifying OA drugs require longitudinal data on cartilage structure. The aim of this study was to analyse the long term and resegmentation precision of quantitative cartilage analysis with magnetic resonance imaging (qMRI) in vivo, and to relate precision errors to the estimated cartilage loss in OA. METHOD: Sagittal MR images of the knee were obtained in 14 individuals, four datasets being acquired in a first imaging session. In 12 subjects, two further datasets were acquired over the next months. Image analysis was performed in the same session for image data obtained under short-term and long-term imaging conditions, and in three different sessions (months apart) for the first data set (resegmentation precision). RESULTS: Long-term precision errors ranged from 1.4% (total knee) to 3.9% (total femur) for cartilage volume and thickness and were only marginally higher than those under short term conditions. In the medial tibia, the error was 84 mm(3) compared with an estimated loss of >1,200 mm(3) in varus OA. Precision errors for resegmentation were somewhat higher, but considerably smaller than the intersubject variability. CONCLUSIONS: Scanner drift and changes in imaging or patient conditions appear not to represent a critical problem in quantitative cartilage analysis with magnetic resonance imaging (qMRI). In longitudinal studies, image analysis of sequential data should be performed within the same post-processing session. Under these conditions, qMRI promises to be a very powerful method to assess structural change of cartilage in OA.     

双能X线骨密度仪精密度和准确度的研究

目的：通过测量长、短期精密度和短期准确度对双能X线吸收法（ dual－energy X－ray absorptiometry ,DXA）骨密度仪进行质量控制。方法①长期精密度：对质量保证（Quality Assurance,QA）模块连续1年的测试数据进行统计分析,分别计算其高、中、低骨密度、均值骨密度、骨矿盐含量、投影面积的变异系数（ coefficient of variation ,CV）;②短期精密度：取连续25天的QA模块测试数据,计算高、中、低骨密度平均值和标准差（standard deviation,SD）,制作Shewhart质控图。另外选取30名志愿者,分别测量L1－4椎体,双侧股骨颈、大粗隆、Ward＇s三角、全髋关节的骨密度（bone mineral density,BMD）值,计算均方根变异系数（ root mean square of the CV ,RMS－CV）;③短期准确度：取连续25天的QA模块测试数据,计算高、中、低骨密度的准确度。结果①长期精密度：QA模块测量高、中、低骨密度、均值骨密度、骨矿盐含量、投影面积的CV分别为0．37％、0．37％、0．41％、0．43％、0．47％、0．12％;②短期精密度：连续25天QA模块测试数据均符合Shewhart 法则;30例受试者L1－4椎体,双侧股骨颈、大粗隆、Ward＇s 三角、全髋关节各测量部位的RMS－CV 分别为1．3％、0．8％、0．9％、1．2％、1．3％、1．5％、1．6％、0．6％、0．6％;③短期准确度：连续25天QA模块测试数据的高、中、低骨密度的准确度分别为－0．07％、0．10％、0．60％。结论进行长、短期精密度和准确度测试能反映双能X线吸收骨密度仪的一致性和可靠性,可有效提高骨质疏松的流行病学研究、诊断、治疗、药物试验研究的可信度。     

In vivo and in vitro precision for bone density measured by dual-energy X-ray absorption

An investigation was made into some of the major sources of error influencing the bone mineral density (BMD) measurements of the lumbar vertebrae, the femoral neck and the greater trochanter. The effect on accuracy and reproducibility of the following parameters was investigated: influence of patient positioning, patient size, scan speed, the technique of scan analysis and the temporal variation in instrument performance.The in vitro precision, both long-term and short-term, was assessed using aluminium phantoms supplied by the manufacturer. For the spine phantom, the precision expressed as a percentage coefficient of variation (%CV) was found to be 0.4% (10 scans) in the short term and 0.55% (15 scans) in the long term. Measured precision (short-term) for the three regions of the femur phantom analysed by the software was 1.3% for the neck of femur, 1.7% for Ward's triangle and 0.6% for the trochanter. Long-term precision was 1.0%, 1.9% and 1.1% respectively. No statistically significant difference was found between long- and short-term results.Short-term in vitro precision on a low density anthropological phantom was 4.1%, 4.2%, 2.4% and 0.61% for neck of femur, Ward's triangle, trochanter and spine respectively.In vivo short-term precision for the lumbar spine (L2–L4), measured by scanning four normal volunteers five times in one session, was found to be 0.8±0.25%. In vivo precision for the femur, measured on seven volunteers was 1.6±0.8% for the neck of femur, 3.2±1.7% for Ward's triangle and 2.2±1.1% for the trochanter.The variation in density results caused solely by analysis was investigated by analysing ten randomly selected normal femoral scans five times on five different days. Again results are expressed as a coefficient of variation and were 1.3±0.8% for the neck of femur, 2.4±1% for Ward's triangle and 0.8±0.7% for the trochanter, suggesting that most of the variation in the femur density results can be attributed to the analysis procedure.     

Calibration and standardization of bone mineral densitometers

Measurements of bone mineral density (BMD) by four 153Gd and two x-ray bone densitometers were compared utilizing spine phantoms that simulated the human lumbar spine. The six instruments provided BMD values that differed by as much as 16%, due to differences as large as 8% in bone mineral content and as large as 7% in bone area. Instrument calibration curves, determined by measuring thin, medium, and thick hydroxyapatite blocks, were linear (r = 0.99) but had different (p less than 0.0001) slopes and intercepts. Serial measurements of spine and total body phantoms were employed to evaluate the long-term stability of 153Gd bone densitometry. These measurements of spine phantom BMD increased 1.0-2.6% (p less than 0.0001) following a software change, and measurements of total body bone density increased 4-6% after 153Gd source replacement. The changes occurred at a time when serial measurements of cylindrical calibration standards were stable, indicating that such simple standards are unable to detect and correct for changes in instrumental response. We conclude that investigators, manufacturers, and government regulatory agencies must develop and implement the following: (1) effective calibration procedures that would assure comparability among instruments, and (2) appropriate quality control phantoms that would allow the confident interpretation of serial patient measurements.