Biomedical subjects

R Barkmann

Publications and source records attributed to R Barkmann.

17 recordsLinked to original sources

PubMed2006

Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs.

The Göttingen minipig is one of the few large animal models that show glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of bone mineral density (BMD) and bone strength in minipigs can be recovered by treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were allocated to 4 groups when they were 30 months old: GC treatment for 8 months (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5 mg/kg body weight. IBN was administered intramuscularly and intermittently with an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and 15. Blood and urine samples were obtained every 2-3 months. After sacrificing the animals lumbar vertebrae L4 were tested mechanically (Young's modulus and ultimate stress). Histomorphometry was performed on L2 and mineral content determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean, p<0.001) during the first 8 months were more than recovered during the following 7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22% (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2) while deoxypyridinoline was comparable. This minipig study demonstrates that GC-induced impairment of bone strength can be effectively and consistently treated by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be monitored in vivo using QCT of the spine and by biochemical analyses, reflecting the changes in bone strength.

Absorptiometry, Photon↗

PubMed2006

A method for the estimation of femoral bone mineral density from variables of ultrasound transmission through the human femur.

Quantitative ultrasound (QUS) measurements at peripheral sites can be used to estimate osteoporotic fracture risk. However, measurements at these sites are less suitable to predict bone mineral density (BMD) or fracture risk at the central skeleton. We investigated whether direct QUS measurements at the femur would allow to estimate dual X-ray absorptiometry (DXA) BMD of the total proximal femur with errors comparable to established DXA accuracy errors. Two independent sets of femora were measured in Kiel (6 f, 4 m, age: 55-90) and Paris (19 f, 20 m age: 45-95) using different benchtop systems in the two laboratories. The femora were scanned in transverse transmission mode using focused US transducers of 500 kHz center frequency. The QUS values were averaged over a region similar to the total hip region of dual X-ray absorptiometry (DXA) measurements. BMD was measured using DXA. SOS and BMD correlated significantly (p<0.0001) in both data sets (R2=0.81-0.93). Correlations between BUA and BMD were also significant at p<0.001, but correlation coefficients were lower (R2=0.61-0.75). Residual errors for the estimation of BMD were 8%-10% for SOS as predictor, and 14%-16% for BUA as predictor. The residual error of 8 to 10% for the estimation of BMD from SOS is comparable to variabilities among different DXA femur subregions and accuracy errors of femoral DXA measurements caused by the impact of soft tissue. It is substantially smaller than the errors of 13% for the estimation of total femur BMD from spine BMD, 14% for the estimation of total femur BMD from calcaneus SOS or 16% for the estimation of ash weight from DXA. The results of the study show that SOS is able to predict total BMD with adequate accuracy. If femoral BMD could be obtained in vivo with comparable accuracy, femoral QUS would be suited for the assessment of bone status at one of the main osteoporotic fracture sites.

Absorptiometry, Photon↗

PubMed2006

Numerical simulation of the dependence of quantitative ultrasonic parameters on trabecular bone microarchitecture and elastic constants.

Finite-difference numerical simulation of ultrasound propagation in complex media such as cancellous bone represents a fertile alternative to analytical approaches because it can manage the complex 3D bone structure by coupling the numerical computation with 3D numerical models of bone microarchitecture obtained from high-resolution imaging modalities. The objective of this work was to assess in silico the sensitivity of ultrasound parameters to controlled changes of microarchitecture and variation of elastic constants. The simulation software uses a finite-difference approach based on the Virieux numerical scheme. An incident plane wave was propagated through a volume of bone of approximately 5 x 5 x 8 mm(3). The volumes were reconstructed from high-resolution micro-computed tomography data. An iterative numerical scenario of "virtual osteoporosis" was implemented using a dedicated image processing algorithm in order to modify the initial 3D microstructures. Numerical computations of wave propagation were performed at each step of the process. The sensitivity to bone material properties was also tested by changing the elastic constants of bone tissue. Our results suggest that ultrasonic variables (slope of the frequency-dependent attenuation coefficient and speed of sound) are mostly influenced by bone volume fraction. However, material properties and structure also appear to play a role. The impact of modifications of the stiffness coefficients remained lower than the variability caused by structural variations. This study emphasizes the potential of numerical computations tools coupled to realistic 3D structures to elucidate the physical mechanisms of interaction between ultrasound and bone structure and to assess the sensitivity of ultrasound variables to different bone properties.

Algorithms↗

PubMed2006

[Quantitative ultrasound].

Methods of quantitative ultrasound (QUS) can be used to obtain knowledge about bone fragility. Comprehensive study results exist showing the power of QUS for the estimation of osteoporotic fracture risk. Nevertheless, the variety of technologies, devices, and variables as well as different degrees of validation of the single devices have to be taken into account. Using methods to simulate ultrasound propagation, the complex interaction between ultrasound and bone could be understood and the propagation could be visualized. Preceding widespread clinical use, it has to be clarified if patients with low QUS values will profit from therapy, as it has been shown for DXA. Moreover, the introduction of quality assurance measures is essential. The user should know the limitations of the methods and be able to interpret the results correctly. Applied in an adequate manner QUS methods could then, due to lower costs and absence of ionizing radiation, become important players in osteoporosis management.

Fractures, Spontaneous↗

PubMed2006

[Parametric biomedical imaging--what defines the quality of quantitative radiological approaches?].

Quantitative parametric imaging approaches provide new perspectives for radiological imaging. These include quantitative 2D, 3D, and 4D visualization options along with the parametric depiction of biological tissue properties and tissue function. This allows the interpretation of radiological data from a biochemical, biomechanical, or physiological perspective. Quantification permits the detection of small changes that are not yet visually apparent, thus allowing application in early disease diagnosis and monitoring therapy with enhanced sensitivity. This review outlines the potential of quantitative parametric imaging methods and demonstrates this on the basis of a few exemplary applications. One field of particular interest, the use of these methods for investigational new drug application studies, is presented. Assessment criteria for judging the quality of quantitative imaging approaches are discussed in the context of the potential and the limitations of these methods. While quantitative parametric imaging methods do not replace but rather supplement established visual interpretation methods in radiology, they do open up new perspectives for diagnosis and prognosis and in particular for monitoring disease progression and therapy.

Algorithms↗

PubMed2005

Optimal prediction of bone mineral density with ultrasonic measurements in excised human femur.

Bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) techniques is the current gold standard for osteoporotic fracture risk prediction. Quantitative ultrasound (QUS) techniques in transmission measurements are, however, increasingly recognized as an alternative approach. It is feasible to select different QUS methods, one type being optimized to assess microarchitectural properties of bone structure and another to assess BMD. Broadband ultrasonic attenuation (BUA) and ultrasonic velocity (UV) measured on the proximal human femur have been shown to be both significantly correlated with BMD. However, a great diversity of algorithms has been reported to measure the time-of-flight used to derive UV values. The purpose of this study was to determine which procedure results in the optimal BMD prediction at the proximal femur from ultrasound measurements. Thirty-eight excised human femurs were measured in transmission with a pair of focused 0.5-MHz central frequency transducers. Two-dimensional scans were performed and radiofrequency (RF) signals were recorded digitally at each scan position. BUA was estimated and eight different signal processing techniques were performed to estimate UV. For each signal-processing technique UV was compared to BMD. We show that the best prediction of BMD was obtained with signal-processing techniques taking into account only the first part of the transmitted signal (r2BMD-SOS = 0.86). Moreover, we show that a linear multiple regression using both BUA and speed of sound (SOS) and applied to site-matched regions of interest improved the accuracy of BMD predictions (r2BMD-SOS/BUA = 0.95). Our results demonstrate that selecting specific signal-processing methods for QUS variables allows optimal assessment of BMD. Correlation is sufficiently high that this specific QUS method can be considered as a good surrogate of BMD.

Absorptiometry, Photon↗

PubMed2005

In vitro speed of sound measurement at intact human femur specimens.

Quantitative ultrasound has been recognized as a useful tool for fracture risk prediction. Current measurement techniques are limited to peripheral skeletal sites. Our objective was to demonstrate the in vitro feasibility of ultrasonic velocity measurements on human proximal femur and to investigate the relationship between velocity and bone mineral density (BMD). Sound velocity images were computed from 2-D scans performed on 38 excised human femurs in transmission at 0.5 MHz. Different regions-of-interest were investigated. Dual x-ray absorptiometry scans have been achieved for BMD measurements in site-matched regions. Our study demonstrates the feasibility of ultrasonic velocity measurements at the hip with reasonable precision (coefficient of variation of 0.3%). The best prediction of BMD was reached in the intertrochanter region (r(2) = 0.91, p < 10(-4)), with a residual error of 0.06 g/cm(2) (10%). Because BMD measured at the femur is the best predictor of hip fracture risk, the highly significant correlation and small residual error found in this study suggest that speed of sound measurement at the femur might be a good candidate for hip fracture risk prediction.

Absorptiometry, Photon↗

PubMed2004

[Quantitative ultrasound for the diagnosis of osteoporosis].

Quantitative ultrasound (QUS) methods are promising tools for the assessment of the bone status in osteoporosis. The techniques are based on changes in speed and amplitude of a broadband ultrasound signal propagating through the bone. However, ultrasound propagation through the anisotropic bone is complex and cannot be described in a simple way. The devices are easy to use, inexpensive, portable, do not use ionizing radiation, and therefore have advantages compared to conventional densitometry. This review discusses the technical basics, current research, clinical applications, points of weakness, and future prospects of QUS. For better understanding ultrasound propagation through bone is visualized with a simulation software.

Bone and Bones↗

PubMed2002

German pediatric reference data for quantitative transverse transmission ultrasound of finger phalanges.

Quantitative ultrasound (QUS) of the finger phalanges is a useful tool in the assessment of disease- or age-related deterioration of bone. For studying the impact of juvenile diseases or growth disorders affecting the skeleton, a reference database for QUS parameters is needed. The aim of this study was to establish a calibrated reference database of parameters of transverse ultrasound transmission through juvenile finger phalanges. A total of 1328 children (650 females, 678 males; ages 3-17 years) were measured in Heidelberg and Kiel in order to establish a German reference database. Highly significant gender-specific correlations (p<0.0001) were found between the QUS parameters amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) versus age, body height and body mass index (BMI). For AD-SoS the correlation coefficients were R2 = 0.64 against age in males and R2 = 0.73 in females, R2 = 0.60 against body height in males and R2 = 0.68 in females, and R2 = 0.19 against BMI in males and R2 = 0.23 in females. For BTT the correlation coefficients were R2 = 0.74 against age in males and R2 = 0.79 in females, R2 = 0.75 against body height in males and R2 = 0.77 in females, and R2 = 0.32 against BMI in males and R2 = 0.35 in females. Age and height were the strongest determinants of QUS results. Gender-specific differences were observed in AD-SoS (significant for ages 11-14 years and for 150-170 cm body height) and in BTT (significant for ages 7 and 11-17 years and for 160-170 cm body height). Tables of QUS parameters versus age and height can serve as a basis for the evaluation of the impact of skeletal diseases or growth disorders on phalangeal QUS. Depending on the type of disease or growth disorder, measurement results can be compared with age- or height- specific reference data. In this way a simple and radiation-free assessment of juvenile skeletal disorders using quantitative ultrasound might be possible in the future.

Adolescent↗

PubMed2001

Correlation of thoracic and lumbar vertebral failure loads with in situ vs. ex situ dual energy X-ray absorptiometry.

In this study we explore the hypothesis that estimates of failure loads in the thoracic spine by lumbar dual energy X-ray absorptiometry (DXA) are compromised of skeletal heterogeneity throughout the spine and artifacts of spinal DXA. We studied the correlation between mechanical failure loads of thoracic and lumbar vertebrae, and that of in situ vs. ex situ lumbar DXA with thoracic and lumbar fracture loads, respectively. One hundred and nineteen subjects (76 female, age 82+/-9yr; 43 male, age 77+/-11yr) were examined under in situ conditions (anterior-posterior direction), the scans being repeated ex situ (lateral projection) in 68 cases. The failure loads of thoracic vertebrae (T) 6 and 10, and lumbar vertebra (L) 3 were determined in axial compression, using a functional 3-segment unit. The correlation between thoracic failure loads (T6 vs. T10) was significantly (p<0.01) higher (r=0.85) than those between thoracic and lumbar vertebrae (r=0.68 and 0.61, respectively). Lateral ex situ DXA displayed a significantly higher correlation (p<0.05) with lumbar vertebral fracture loads than in situ anterior-posterior DXA (r=0.85 vs. 0.71), but the correlation of thoracic failure loads with lateral ex situ lumbar DXA was similar to that obtained in situ in anterior-posterior direction (r=0.69 vs. 0.69 for T10, and r=0.61 vs. 0.65 for T6). The correlation between fracture loads of different spinal segments, and between DXA and failure loads was not significantly different between men and women. The results demonstrate a substantial heterogeneity of mechanical competence throughout the spine in elderly individuals. Because of the high incidence of fractures in the thoracic spine, these findings suggest that, clinically, lateral DXA involves no relevant advantage over anterior-posterior measurements of the lumbar spine.

Absorptiometry, Photon↗

PubMed2001

Assessment of phalangeal bone loss in patients with rheumatoid arthritis by quantitative ultrasound.

OBJECTIVE: Periarticular osteopenia is an early radiological sign of rheumatoid arthritis (RA). Quantitative ultrasound (QUS) devices have recently been shown to be useful for assessing osteoporosis. In this study the capability of a transportable and easy to use QUS device to detect skeletal impairment of the finger phalanges in patients with RA was investigated. METHODS: In a cross sectional study 83 women (30 controls, 29 with glucocorticosteroid (GC) treated RA, and 24 with GC treated vasculitis) were examined. QUS measurements were obtained at the metaphyses of the proximal phalanges II-V and directly at the proximal interphalangeal joints II-IV with a DBM Sonic 1200 (IGEA, Italy) QUS device. Amplitude dependent speed of sound (AD-SoS) was evaluated. In 23 of the patients with RA, hand radiographs were evaluated. RESULTS: Significant differences between patients with RA and the other groups were found for AD-SoS at both measurement sites. Compared with age matched controls, the AD-SoS of patients with RA was lowered by two and three standard deviations at the metaphysis and joint, respectively. Fingers of patients with RA without erosions (Larsen score 0-I) already had significantly decreased QUS values, which deteriorated further with the development of erosions (Larsen II-V). CONCLUSION: This study indicates that QUS is sensitive to phalangeal periarticular bone loss in RA. QUS is a quick, simple, and inexpensive method free of ionising radiation that appears to be suited to detection of early stages of periarticular bone loss. Its clinical use in the assessment of early RA should be further evaluated in prospective studies.

Adult↗

PubMed2000

Assessment of the geometry of human finger phalanges using quantitative ultrasound in vivo.

Quantitative Ultrasound (QUS) methods have been shown to be useful in the assessment of bone status. Nevertheless, ultrasound transmission depends on a variety of skeletal parameters, and a detailed understanding of ultrasound propagation through bone is important for the accurate interpretation of QUS results. In this study we wanted to elucidate the pathways of an ultrasound wave through finger phalanges and determine correlations between geometric and QUS parameters. Phalanges of a subject group were measured using QUS and magnetic resonance imaging (MRI). MRI was used for the derivation of the geometric parameters. Similar assessments were performed on cylindrical tubes and with a simulation program. New parameters related to speed of sound (SOS) and amplitude of the wave (A2P) were calculated. Strong correlations between QUS parameters and morphologic cross-sectional areas were observed in vivo and in phantoms. Similar correlations could be found in the calculations using the simulation software. Cross-sectional cortical area, medullary canal area and relative cortical area could be calculated from the QUS parameters (subjects: R2 = 0.71 for cortical area, R2 = 0.45 for medullary canal area and R2 = 0.61 for relative cortical area; phantoms: R2 = 0.98 for cortical area, R2 = 0.78 for medullary canal area and R2 = 0.77 for relative cortical area). In vivo, phantom and simulation results consistently showed that SOS was correlated with cortical area but not with medullary canal area while the opposite was found for A2P. Pathways of the ultrasound wave through solid cortical bone and the medullary canal could be identified and the propagation of the wave could be depicted. These results help to interpret QUS findings and provide information that may be helpful in improving the performance of QUS.

Adult↗

PubMed2000

A new method for quantitative ultrasound measurements at multiple skeletal sites: first results of precision and fracture discrimination.

We investigated a new multisite quantitative ultrasound device that measures the acoustic velocity in axial transmission mode along the cortex. Using a prototype of the Omnisense (Sunlight Ultrasound Technologies, Rehovot, Israel), we tested the performance of this instrument at four sites of the skeleton: radius, ulna, metacarpal, and phalanx. Intraobserver (interobserver) precision errors ranged from 0.2% to 0.3% (0.3% to 0.7%) for triplicate measurements with repositioning. Fracture discrimination was tested by comparing a group of 34 women who had previously suffered a fracture of the hip, spine, ankle, or forearm to a group of 28 healthy women who had not suffered a fracture. Age-adjusted standardized odds ratios ranged from 1.6 to 4.5. Except for the ulna the sites showed a significant fracture discrimination (p < 0.01). The areas under the receiver operating curves (ROC) curves were from 0.88 to 0.89 for radius, metacarpal, and phalanx. A combination of the results from the three sites showed a significant increase of the ROC area to 0.95 (p < 0. 05). Our results show promising performance of this new device. The ability to measure a large variety of sites and the potential to combine these measurements are promising with regard to optimizing fracture risk assessment.

Aged↗

PubMed2000

[Quantitative ultrasonic diagnosis for the assessment of osteoporosis].

In recent years Quantitative Ultrasound (QUS) approaches have increasingly been used for the assessment of osteoporosis. Extensive study results exist for the estimation of osteoporotic fracture risk. Also, results exist for the analysis of properties which characterize osteoporosis--low bone mass and deterioration of bone architecture. However, the existence of different methods, devices and parameters has to be taken into account. Moreover, the status of the evaluation is different for each type of device. Measures of quality assurance and in-depth knowledge about limitations of the approach are of substantial importance for clinical use. Because of the lack of ionising radiation and their lower cost, QUS approaches--if used appropriately--can play an important role in the assessment of osteoporotic fracture risk.

Bone Density↗

PubMed1999

[Quantitative ultrasound. State of the art 1999].

In recent years Quantitative Ultrasound (QUS) approaches have increasingly been used for the assessment of osteoporosis. The development of new technologies has accelerated, and today a number of different devices are commercially available. For a balanced evaluation of the approaches one needs to recognise two issues: There are different applications for QUS, and there are different QUS approaches and devices. Regarding the applications, today the main area for use of QUS approaches is the assessment of a fracture risk. For use in monitoring and diagnosis, further advances and studies are required. Regarding the various approaches, one needs to recognise the differences between the measurement parameters Speed Of Sound (SOS) and Broadband Ultrasound Attenuation (BUA), the different measurement sites and the different technologies employed. Moreover, some of the earlier devices are very well validated whereas newer machines may feature more advanced technology--which, however, needs to be tested and validated. Whatever the choice of a device will be, adequate and regularly performed measures for quality assurance and in-depth knowledge on the general and device specific limitations of the approach are of substantial importance. When used appropriately, QUS devices can play an important role in the assessment of osteoporosis.

Humans↗

PubMed1999

Does combining the results from multiple bone sites measured by a new quantitative ultrasound device improve discrimination of hip fracture?

There is a growing interest in the use of quantitative ultrasound (QUS) measurements as an alternative to current radiation-based bone densitometry techniques for the noninvasive assessment of fracture risk. While most of the commercialized ultrasound devices measure only single predefined peripheral skeletal sites, the Omnisense prototype (Sunlight Ltd., Israel) can be used on multiple bones, including the spinous processes. In this study, we examined the ability of speed of sound measured at the calcaneus, distal third and ultradistal radius, proximal third phalanx, metacarpal, capitate, patella, and the posterior process of the thoracic spine to differentiate subjects with hip fractures from normal controls. Seventy-nine postmenopausal Caucasian Israeli women who had sustained an atraumatic fracture of the proximal femur within the last 6 months were recruited from the local population (mean age 80 +/- 8.9 years). As controls, 295 postmenopausal Caucasian Israeli women without osteoporotic fractures were also included (mean age 70 +/- 8.7 years). Discrimination of hip fractures with QUS at all ultrasound sites was highly statistically significant (p < 0.01) (odds ratios [ORs] = 1.4-3.0; area under the ROC curve [AUC] 77-92%), except for the hand metacarpal. Distal radius and calcaneus measurements (ORs = 2.4 and 3.0) were the best discriminators of hip fracture patients from controls. Using a forward selective linear regression model, the discriminator values of combined assessment at two sites were investigated. There was moderate improvement in diagnostic value, but the best combination was the calcaneus with the distal radius, which improved the AUC by 3% and raised both the sensitivity and specificity to 94%. These data demonstrate the encouraging potential of improving discrimination of hip fracture by using multiple-site ultrasonic measurements.

Aged↗

PubMed1998

[Ultrasound--already clinically relevant?].

The rapid development of Quantitative Ultrasound (QUS) methods in recent years allows to use these devices in a clinical setting. Their primary role is the assessment of fracture risk due to osteoporosis. Further investigations are required for use of QUS for monitoring and diagnostic purposes. Differences between the QUS parameters, Speed of Sound (SOS) and Broadband Ultrasound Attenuation (BUA), between different measurement sites and measurement technology need to be appreciated. Consequently, QUS devices need to be validated individually. In addition, adequate quality assurance measures need to be implemented. QUS and bone densitometry have different complementing features and both should find their place in the clinical arena. These recent developments open up the opportunity to reduce the number of fractures by targeted diagnostic assessments which should lead to medical progress and should also bring along socio-economical advantages.

Bone Density↗