Mikko Hakulinen

Bio: Mikko Hakulinen is an academic researcher from University of Eastern Finland. The author has contributed to research in topics: Bone mineral & Ultrasound. The author has an hindex of 22, co-authored 47 publications receiving 1195 citations.

Ultrasonic characterization of human trabecular bone microstructure.

Abstract: New quantitative ultrasound (QUS) techniques involving ultrasound backscattering have been introduced for the assessment of bone quality. QUS parameters are affected by the transducer characteristics, e.g. frequency range, wave and pulse length. Although frequency-dependent backscattering has been studied extensively, understanding of the ultrasound scattering phenomenon in trabecular bone is still limited. In the present study, the relationships between QUS parameters and the microstructure of human trabecular bone were investigated experimentally and by using numerical simulations. Speed of sound (SOS), normalized broadband ultrasound attenuation (nBUA), average attenuation, integrated reflection coefficient (IRC) and broadband ultrasound backscatter (BUB) were measured for 26 human trabecular bone cylinders. Subsequently, a high-resolution microCT system was used to determine the microstructural parameters. Moreover, based on the sample-specific microCT data, a numerical model for ultrasound propagation was developed for the simulation of experimental measurements. Experimentally, significant relationships between the QUS parameters and microstructural parameters were demonstrated. The relationships were dependent on the frequency, and the strongest association (r = 0.88) between SOS and structural parameters was observed at a centre frequency of 5 MHz. nBUA, average attenuation, IRC and BUB showed somewhat lower linear correlations with the structural properties at a centre frequency of 5 MHz, as compared to those determined at lower frequencies. Multiple regression analyses revealed that the variation of acoustic parameters could best be explained by parameters reflecting the amount of mineralized tissue. A principal component analysis demonstrated that the strongest determinants of BUB and IRC were related to the trabecular structure. However, other structural characteristics contributed significantly to the prediction of the acoustic parameters as well. The two-dimensional numerical model introduced in the present study demonstrated good agreement with the experimental measurements. However, further studies with the simulation model are warranted to systematically investigate the relation between the structural parameters and ultrasound scattering.

Ability of ultrasound backscattering to predict mechanical properties of bovine trabecular bone.

Abstract: Ultrasound (US) backscatter measurements have been proposed for the quantitative evaluation of bone quality. In this study, we explored the ability of broadband US backscatter (BUB) and integrated reflection coefficient (IRC) to predict density and mechanical properties of trabecular bone, as compared to normalized broadband US attenuation (nBUA) and speed of sound (SOS). These acoustic parameters were measured in 41 in vitro samples of bovine trabecular bone and correlated with a number of mechanical parameters and with volumetric bone mineral density (BMDvol). BUB correlated statistically significantly with the volumetric bone mineral density (r = 0.61, p < 0.01), Young’s modulus (r = 0.40, p < 0.01) and ultimate strength (r = 0.40, p < 0.01). IRC was even more strongly correlated with BMDvol (r = 0.92, p < 0.01) and most of the mechanical parameters (0.81 < r < 0.85). Strong correlations were also found between mechanical parameters and SOS (0.87 < r < 0.90). No significant correlation was found between attenuation (nBUA) and either BMDvol or mechanical parameters. Reproducibilities (standardized CV%) of BUB (3.5%) and IRC (1.5%) were comparable to those of nBUA (2.3%) and SOS (0.5%). To conclude, BUB and IRC are promising parameters for the evaluation of density and mechanical properties of trabecular bone. Advantageously, BUB and IRC can be determined with a single transducer, hypothetically enabling measurements at many clinically relevant fracture sites. (E-mail: Mikko.Hakulinen@uku.fi)

Assessment of body composition by dual-energy X-ray absorptiometry, bioimpedance analysis and anthropometrics in children: the Physical Activity and Nutrition in Children study.

Abstract: Summary Objective and methods We compared InBody720 segmental multifrequency bioimpedance analysis (SMF-BIA) with Lunar Prodigy Advance dual-energy X-ray absorptiometry (DXA) in assessment of body composition among 178 predominantly prepubertal children. Segmental agreement analysis of body compartments was carried out, and inter-relationships of anthropometric and other measures of body composition were defined. Moreover, the relations of different reference criteria for excess body fat were evaluated. Results The prevalence of excess body fat varies greatly according to the used criteria. Intraclass and Pearson's correlations between SMF-BIA and DXA were >0·92 in total body and >0·74 in regional measures. SMF-BIA underestimated percentage body fat (%BF) and fat mass (FM), and overestimated lean mass (LM) and percentage LM with significant offset trend bias. Higher adiposity increased offsets, and overall agreement was poorer in girls. On average, %BF offsets (girls/boys) and limits of agreement (LA) were 3·9/1·6% [(−)1·4–9·2%/(−)3·4–6·7%]. Interestingly percentage offsets of fat content (%BF: 18·9/10·1%, FM: 18·8/11·1%) showed no significant bias trends indicating that the corresponding absolute methodological offset depends on the amount of fat content. The smallest percentage offset was found with LM: 4·3/0·1%, referring offset (LA) of 0·88/0·03 kg (±2·05/±1·71 kg). Correspondingly, segmental LM had poorer agreement than total body LM. All anthropometrics except for the waist-to-hip ratio showed strong correlations (r = 0·76–0·95) with abdominal and total body fat. Conclusion Segmental multifrequency bioimpedance analysis is precise enough for total-LM analysis and had also sufficient trueness for total body composition analysis to be used in epidemiological purposes. There is need to generate scientifically and clinically relevant criteria and reference values for excess body fat.

Multi-site bone ultrasound measurements in elderly women with and without previous hip fractures

Abstract: About 75% of patients suffering from osteoporosis are not diagnosed. This study describes a multi-site bone ultrasound method for osteoporosis diagnostics. In comparison with axial dual energy X-ray absorptiometry (DXA), the ultrasound method showed good diagnostic performance and could discriminate fracture subjects among elderly females. Axial DXA, the gold standard diagnostic method for osteoporosis, predicts fractures only moderately. At present, no reliable diagnostic methods are available at the primary health care level. Here, a multi-site ultrasound method is proposed for osteoporosis diagnostics. Thirty elderly women were examined using the ultrasound backscatter measurements in proximal femur, proximal radius, proximal and distal tibia in vivo. First, we predicted the areal bone mineral density (BMD) at femoral neck by ultrasound measurements in tibia combined with specific subject characteristics (density index, DI) and, second, we tested the ability of ultrasound backscatter measurements at proximal femur to discriminate between individuals with previously fractured hips from those without fractures. Areal BMD was determined by axial DXA. Combined ultrasound parameters, cortical thickness at distal and proximal tibia, with age and weight of the subject, provided a significant estimate of BMDneck (r = 0.86, p < 0.001, n = 30). When inserted into FRAX (World Health Organization fracture risk assessment tool), the DI indicated the same treatment proposal as the BMDneck with 86% sensitivity and 100% specificity. The receiver operating characteristic analyses, with a combination of ultrasound parameters and patient characteristics, discriminated fracture subjects from the controls similarly as the model combining BMDneck and patient characteristics. For the first time, ultrasound backscatter measurements of proximal femur were conducted in vivo. The results indicate that ultrasound parameters, combined with patient characteristics, may provide a means for osteoporosis diagnostics.

Prediction of density and mechanical properties of human trabecular bone in vitro by using ultrasound transmission and backscattering measurements at 0.2-6.7 MHz frequency range.

Abstract: The ultrasound (US) backscattering method has been introduced as an alternative for the through-transmission measurement of sound attenuation and speed in diagnosis of osteoporosis. Both attenuation and backscattering depend strongly on the US frequency. In this study, 20 human trabecular bone samples were measured in transmission and pulse-echo geometry in vitro. The aim of the study was to find the most sensitive frequency range for the quantitative ultrasound (QUS) analyses. Normalized broadband US attenuation (nBUA), speed of sound (SOS), broadband US backscatter (BUB) and integrated reflection coefficient (IRC) were determined for each sample. The samples were spatially scanned with five pairs of US transducers covering a frequency range of 0.2-6.7 MHz. Furthermore, mechanical properties and density of the same samples were determined. At all frequencies, SOS, BUB and IRC showed statistically significant linear correlations with the mechanical properties or density of human trabecular bone (0.51 < r < 0.82, 0.54 < r < 0.81 and 0.70 < r < 0.85, respectively). In contrast to SOS, IRC and BUB, nBUA showed statistically significant correlations with mechanical parameters or density at the centre frequency of 1 MHz only. Our results suggest that frequencies up to 5 MHz can be useful in QUS analyses for the prediction of bone mechanical properties and density. Since the use of higher frequencies provides better axial and spatial resolution, improved structural analyses may be possible. While extensive attenuation of high frequencies in trabecular bone limits the clinically feasible frequency range, selection of optimal frequency range for in vivo QUS application should be carefully considered.

Electrical conductivity of tissue at frequencies below 1 MHz.

Abstract: A two-pronged approach, review and measurement, has been adopted to characterize the conductivity of tissues at frequencies below 1 MHz. The review covers data published in the last decade and earlier data not included in recent reviews. The measurements were carried out on pig tissue, in vivo, and pig body fluids in vitro. Conductivity data have been obtained for skeletal and myocardial muscle, liver, skull, fat, lung and body fluids (blood, bile, CSF and urine). A critical analysis of the data highlights their usefulness and limitations and enables suggestions to be made for measuring the electrical properties of tissues.

Pitfalls in the measurement of muscle mass: a need for a reference standard

Abstract: BACKGROUND: All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. METHODS: Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings were organized for the whole group to make amendments and discuss further recommendations. RESULTS: A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X-ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. CONCLUSIONS: Based on the feasibility, accuracy, safety, and low cost, dual energy X-ray absorptiometry can be considered as the reference standard for measuring muscle mass.