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Biomedical subjects

Pascal Laugier

Publications and source records attributed to Pascal Laugier.

At least 19 recordsLinked to original sources

Experimental evaluation of bone quality measuring speed of sound in cadaver mandibles.

OBJECTIVES: To demonstrate in vitro the feasibility of speed of sound (SOS) measurements through the mandible and to investigate the relationships between mandibular SOS, local bone mineral density (BMD), and the ratio between trabecular and cortical thicknesses (Tb.Th/Cort.Th). The long-term goal is to find a safe, simple test for bone quality in sites for dental implant placement. METHODS: Excised human mandibles (N = 23) were used for the measurement of sound transmission with two 1.6 MHz transducers. Three regions of interest (ROIs) were selected in each of the specimens, namely incisor, premolar, and molar regions. To determine short-term precision, 10 measurements (with repositioning between measures) were performed for each ROI. Local BMD and mandibular cross-sectional morphological characteristics were determined by dual x-ray absorptiometry (DXA) and computed tomography (CT). RESULTS: The coefficient of variation for SOS was found to be 1%. SOS measurements at different sites were significantly different. A significant linear relationship was found between SOS and BMD (r2 = 0.62; P < .0001), whereas a nonlinear relationship was found between SOS and Tb.Th/Cort.Th (r2 = 0.53; P < .0001). CONCLUSION: This in vitro study demonstrated the feasibility of SOS measurement through the mandible. Mandibular SOS reflects local BMD and Tb.Th/Cort.Th. In vivo studies are now required to confirm the predictive power of SOS measurement for bone quality assessment and its potential usefulness as a clinical diagnostic technique.

Absorptiometry, Photon↗

Assessment of bone structure and acoustic impedance in C3H and BL6 mice using high resolution scanning acoustic microscopy.

Two hundred-MHz time-resolved scanning acoustic microscopy was applied for the investigation of acoustic and structural bone properties of mice from two inbred strains. Transverse sections of femur taken from 5 C57BL/6J@Ico and 5 C3H/HeJ@Ico mice were explored. Both strains had the same bone diameter, but the C3H/HeJ@Ico mice had greater cortical thickness, smaller cancellous diameter, and greater acoustic impedance values than C57BL/6J@Ico mice. The strong differences in the measured acoustic impedances among the two inbred strains indicate that the impedance is a good parameter to detect genetic variations of the skeletal phenotype in small animal models.

Animals↗

Derivation of elastic stiffness from site-matched mineral density and acoustic impedance maps.

200 MHz acoustic impedance maps and site-matched synchrotron radiation micro computed tomography (SR-muCT) maps of tissue degree of mineralization of bone (DMB) were used to derive the elastic coefficient c(33) in cross sections of human cortical bone. To accomplish this goal, a model was developed to relate the DMB accessible with SR-muCT to mass density. The formulation incorporates the volume fractions and densities of the major bone tissue components (collagen, mineral and water), and accounts for tissue porosity. We found that the mass density can be well modelled by a second-order polynomial fit to DMB (R(2) = 0.999) and appears to be consistent with measurements of many different types of mineralized tissues. The derived elastic coefficient c(33) correlated more strongly with the acoustic impedance (R(2) = 0.996) than with mass density (R(2) = 0.310). This finding suggests that estimates of c(33) made from measurements of the acoustic impedance are more reliable than those made from density measurements. Mass density and elastic coefficient were in the range between 1.66 and 2.00 g cm(-3) and 14.8 and 75.4 GPa, respectively. Although SAM inspection is limited to the evaluation of carefully prepared sample surfaces, it provides a two-dimensional quantitative estimate of elastic tissue properties at the tissue level.

Acoustics↗

High-frequency ultrasound detection and follow-up of Wilms' tumor in the mouse.

The goal of this study was to validate high-frequency (24 MHz) ultrasound imaging techniques for early detection and follow-up of renal tumors in a murine Wilms' tumor model (n = 26). For 11 mice, maximum tumor dimensions were estimated from images along three orthogonal axes for comparison with posteuthanasia caliper and histologic measurements. Tumor size in the 15 remaining mice was checked biweekly. The mice were then euthanized and histologic study assessed tumor position and nature. Tumors were detected in vivo between 7 to 14 days after injection of tumor-inducing cells. Tumor maximum cross-sectional area varied from 0.07 mm2 to 5.7 mm2 at the time of initial detection. The relative r.m.s. error between ultrasonic and histologic estimations of maximum cross-sectional area was estimated to be 19%. Results demonstrate feasibility of noninvasive ultrasound biomicroscopy early detection and characterization of renal tumor development for longitudinal monitoring of the same animal.

Animals↗

Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

Acoustics↗

Effects of frequency-dependent attenuation and velocity dispersion on in vitro ultrasound velocity measurements in intact human femur specimens.

Numerous studies have shown that ultrasonic velocity measured in bone provides a good assessment of osteoporotic fracture risk. However, a lack of standardization of signal processing techniques used to compute the speed of sound (SOS) complicates the comparison between data obtained with different commercial devices. In this study, 38 intact femurs were tested using a through-transmission technique and SOS determined using different techniques. The resulting difference in measured SOS was determined as functions of the attenuation and the velocity dispersion. A numerical simulation was used to explain how attenuation and dispersion impact two different SOS measurements (group velocity, velocity based on the first zero crossing of the signal). A new method aimed at compensating for attenuation was devised and led to a significant reduction in the difference between SOS obtained with both signal processing techniques. A comparison between SOS and X-ray density measurements indicated that the best correlation was reached for SOS based on the first zero crossing apparently because it used a marker located in the early part of the signal and was less sensitive to multipath interference. The conclusion is that first zero crossing velocity may be preferred to group velocity for ultrasonic assessment at this potential fracture site.

Aged↗

Estimation of trabecular thickness using ultrasonic backcatter.

We present a method to estimate trabecular thickness (Tb.Th) in trabecular bones from ultrasound backscatter measurements. The estimation scheme is based on a nonlinear adjustment of predictions from a model to experimental data. The model assumes weak scattering from bone, where scattering is assumed to arise from the elastic solid trabeculae. The fluctuations of acoustical properties between bone tissue and the saturating fluid are assumed to be random and are described by the 3-D spatial autocorrelation function of the medium. In this paper, a Gaussian autocorrelation function is used. The inversion procedure is applied to a set of data measured on 33 femoral bone specimens. Results show that the model can predict both the magnitude and the frequency-dependence of the backscatter coefficient (root mean square error RMSE = 1 dB). The estimated trabecular thickness values are compared to the true trabecular thickness measured on high resolution microcomputed tomography 3-D reconstruction of bones microarchitecture. A close agreement is obtained on average over the group of specimens between predictions and the reference values: true Tb.Th is 132 +/- 12 microm and estimated Tb.Th is 134 +/- 15 microm. However, a moderate correlation between actual and estimated Tb.Th values is found (R2 = 0.44, p<10(-4), RMSE = 8.7 microm) suggesting a modest predictability at the individual level. Sources for the variability of the estimator are studied. Using synthetic rf signals, we demonstrate that the fundamental limitation of the estimator due to speckle noise is approximately 5 microm. Taking into account the measurement errors, the total uncertainty on Tb.Th estimates is of the order of 7 microm. The influence of the attenuation compensation function used to derive the backscatter coefficient is studied. In particular, we demonstrate the necessity of compensating for the effect of the gating time window. The results are discussed with respect to their meaningful clinical value. The requirements to be fulfilled by the performance of the technique change with regard to the question being posed. Two different strategies are examined: 1. characterize trabecular thickness without consideration of bone quantity (or bone mineral density) and 2. estimate trabecular thickness after adjustment for BMD. Considering the first strategy, a comparison between the precision of our estimator and the biological variability leads us to the conclusion that our estimator should only permit to distinguish between micro-architectures characterized by extreme values of trabecular thickness (i.e., very thin or very thick trabecular thickness). In this respect, it would be interesting to test whether the estimator is able to discriminate between rod-like (thin) and plate-like (thick) structures that are known to influence differently bone strength. The second strategy is more demanding in terms of technique performance and our estimator is not able yet to catch small differences in Tb.Th values expected after adjustment to bone density. Progress in the field will require a significant reduction in speckle noise and measurement errors and/or the development of other and more efficient microstructural estimators.

Artifacts↗

Ultrasonic backscatter and attenuation (11-27 MHz) variation with collagen fiber distribution in ex vivo human dermis.

This ex vivo study explores the relationship of ultrasonic attenuation and backscatter to dermal microarchitecture by comparing ultrasonic measurements of these parameters (11-27 MHz) to a microscopic analysis of three parameters describing the collagen distribution (mean thickness and spacing of collagen bundles along the insonification direction and the percent area occupied by collagen). Skin samples (N= 31) were obtained from patients undergoing breast or abdominal reduction surgery. Radio-frequency (rf) signals were acquired in a B-scan format using an ultrasound system developed for skin imaging (Ultrasons Technologies, Tours, France). Ultrasonic data were analyzed to calculate average integrated backscatter (IBS in dB) and frequency dependence of backscatter (n, dimensionless) of each specimen at depths centered approximately 370,620 and 880 microm beneath the skin surface. Average integrated attenuation coefficient (IA in dB.cm(-1)) and frequency dependence of attenuation coefficient (beta in dB.cm(-1).MHz(-1)) were estimated across the depth between 240 and 1,000 microm. The three collagen distribution parameters were estimated using digitized microcopic fields from matched regions of histological sections stained with hematoxylin-eosin-saffron. No significant correlation was identified between collagen distribution parameters and IA or beta. For the most superficial depth studied in abdominal skin, n was inversely correlated to collagen bundle thickness (r = -0.67,p = 0.002) and percent area (r = -0.65,p = 0.003). At the same depth, IBS was inversely correlated to percent area of collagen (r = -0.51,p = 0.03). The rather high collagen packing (48 to 82% area) measured in histological sections and the inverse relationship observed between IBS and percent area of collagen suggest that a packing factor should be included in models relating skin collagen distribution to ultrasound spectral parameters. A better understanding of the relationship between ultrasound parameters and the microarchitecture of the dermis should help to interpret changes in ultrasonic parameters observed during in vivo ultrasonic skin examinations.

Abdomen↗

Three-dimensional simulation of ultrasound propagation through trabecular bone structures measured by synchrotron microtomography.

Three-dimensional numerical simulations of ultrasound transmission were performed through 31 trabecular bone samples measured by synchrotron microtomography. The synchrotron microtomography provided high resolution 3D mappings of bone structures, which were used as the input geometry in the simulation software developed in our laboratory. While absorption (i.e. the absorption of ultrasound through dissipative mechanisms) was not taken into account in the algorithm, the simulations reproduced major phenomena observed in real through-transmission experiments in trabecular bone. The simulated attenuation (i.e. the decrease of the transmitted ultrasonic energy) varies linearly with frequency in the MHz frequency range. Both the speed of sound (SOS) and the slope of the normalized frequency-dependent attenuation (nBUA) increase with the bone volume fraction. Twenty-five out of the thirty-one samples exhibited negative velocity dispersion. One sample was rotated to align the main orientation of the trabecular structure with the direction of ultrasonic propagation, leading to the observation of a fast and a slow wave. Coupling numerical simulation with real bone architecture therefore provides a powerful tool to investigate the physics of ultrasound propagation in trabecular structures. As an illustration, comparison between results obtained on bone modelled either as a fluid or a solid structure suggested the major role of mode conversion of the incident acoustic wave to shear waves in bone to explain the large contribution of scattering to the overall attenuation.

Algorithms↗

Progress towards in vitro quantitative imaging of human femur using compound quantitative ultrasonic tomography.

The objective of this study is to make cross-sectional ultrasonic quantitative tomography of the diaphysis of long bones. Ultrasonic propagation in bones is affected by the severe mismatch between the acoustic properties of this biological solid and those of the surrounding soft medium, namely, the soft tissues in vivo or water in vitro. Bone imaging is then a nonlinear inverse-scattering problem. In this paper, we showed that in vitro quantitative images of sound velocities in a human femur cross section could be reconstructed by combining ultrasonic reflection tomography (URT), which provides images of the macroscopic structure of the bone, and ultrasonic transmission tomography (UTT), which provides quantitative images of the sound velocity. For the shape, we developed an image-processing tool to extract the external and internal boundaries and cortical thickness measurements. For velocity mapping, we used a wavelet analysis tool adapted to ultrasound, which allowed us to detect precisely the time of flight from the transmitted signals. A brief review of the ultrasonic tomography that we developed using correction algorithms of the wavepaths and compensation procedures are presented. Also shown are the first results of our analyses on models and specimens of long bone using our new iterative quantitative protocol.

Algorithms↗

Bone status in primary hyperparathyroidism assessed by regional bone mineral density from the whole body scan and QUS imaging at calcaneus.

To assess the bone mineral density status in primary hyperparathyroidism (PHPT), we studied 64 females with PHPT and 17 healthy women. Regional BMD (arms, trunk, legs) from the whole body scan and conventional sites (lumbar spine, femur, radius) were assessed by DXA. Quantitative ultrasound (QUS) imaging measurements were performed at calcaneus. Sixteen women had history of renal lithiasis, 11 had low impact fracture and 37 women had neither renal lithiasis nor fracture. In the entire group, the mean Z-scores were significantly decreased at all sites (lumbar spine, femur, radius). In all clinical subgroups, the mean Z-scores were significantly decreased at radius. The mean Z-scores in premenopausal women were significantly decreased comparatively to postmenopausal women at lumbar spine and femur. In a group of PHPT females matched to controls for age and BMI, only BMD values at radius were lower in PHPT patients than in control (P < 0.03). However, from the whole body scan data, all sites but no trunk were significantly involved in PHPT patients (P < 0.04). Using QUS measurements at calcaneus, the BUA but not SOS in PHPT females was significantly lower (P = 0.03) than in controls. Our results suggest that low BMD at lumbar spine and femur is encountered preferentially in premenopausal women. The BMD decrease predominates at limbs in PHPT with presumably a gradient from proximal to distal part of the limbs. Indeed, the distal part of the limbs are the most affected areas in PHPT whatever the amount of cortical or trabecular bone.

Absorptiometry, Photon↗

Recent developments in trabecular bone characterization using ultrasound.

Currently available quantitative ultrasound technologies to assess cancellous bone are based on the measurements in transmission of speed of sound or slope of frequency-dependent attenuation (so called broadband ultrasonic attenuation). These two parameters are now considered as surrogate markers of site-matched bone mineral density. The ability of ultrasound techniques to provide non-bone mineral density-related bone properties (eg, microstructure) has not been clearly demonstrated yet. This is mainly because of two factors: a lack of understanding of ultrasound propagation with clear identification of the different underlying physical interactions; and the difficulty of performing experiments because of the limited sample size, the large number of statistical relationships to be tested with multiple variables, and the usual strong covariance observed between bone quantity and microarchitecture. The aim of this paper is to review the most recent development in the field of ultrasound characterization of trabecular bone. We present research work on ultrasound backscatter and how it could be used to estimate microarchitectural properties independently of bone quantity, and the first promising results obtained for the estimation of trabecular thickness. We then introduce numeric simulations of wave propagation through trabecular microarchitecture and show how it could contribute to elucidate and better characterize the physical underlying physics and result in more predictive models. These innovative acquisition schemes and the possibility of virtual experiments should altogether contribute to rapid advancement of ultrasonic bone characterization.

Bone Density↗

Monitoring cell adhesion processes on bioactive polymers with the quartz crystal resonator technique.

The Thickness Shear Mode (TSM) quartz crystal resonator has been extensively used as sensitive sensor in various electrochemical and biological applications. This technique based on the propagation of an ultrasonic shear wave generated by a sinusoidal electric field through a piezoelectric quartz resonator, provides a non-destructive and powerful means to probe changes at solid-solid or solid-liquid interfaces. In this study, TSM was used to characterize cell-polymer interactions developing during the cell adhesion process. TSM sensing was used to monitor the inhibiting properties of bioactive polymers towards fibroblast McCoy adhesion processes. For this purpose, thin films of various bioactive polymers exhibiting either carboxylate or/and sulfonate functional groups were deposited onto the TSM. Measurements of the time variation of the electrical motional resistance in the vicinity of the mechanical sensor resonant frequency were performed as the quartz crystal resonator was either coated with the continuous polymer phase or polymer plus cell suspensions. Cell adhesion processes on these surfaces was investigated by cell counting and the quartz resonator-based technique. Inhibition of fibroblast McCoy adhesion onto thin polymer films of various chemical compositions was analyzed and discussed in the perspective of a possible application of these bioactive polymers to fabricate intraocular lenses able to prevent secondary cataract phenomena.

Biocompatible Materials↗

Bone microstructure and elastic tissue properties are reflected in QUS axial transmission measurements.

Accurate clinical interpretation of the sound velocity derived from axial transmission devices requires a detailed understanding of the propagation phenomena involved and of the bone factors that have an impact on measurements. In the low megahertz range, ultrasonic propagation in cortical bone depends on anisotropic elastic tissue properties, porosity and the cortical geometry (e.g., thickness). We investigated 10 human radius samples from a previous biaxial transmission study using a 50-MHz scanning acoustic microscope (SAM) and synchrotron radiation microcomputed tomography. The relationships between low-frequency axial transmission sound speed at 1 and 2 MHz, structural properties (cortical width Ct.Wi, porosity, Haversian canal density and material properties (acoustic impedance, mineral density) on site-matched cross-sections were investigated. Significant linear multivariate regression models (1 MHz: R(2) = 0.84, p < 10(-4), root-mean-square error (RMSE) = 38 m/s, 2 MHz: R(2) = 0.65, p < 10(-4), RMSE = 48 m/s) were found for the combination of Ct.Wi with porosity and impedance. A new model was derived that accounts for the nonlinear dispersion relation with Ct.Wi and predicts axial transmission velocities measured at different ultrasonic frequencies (R(2) = 0.69, p < 10(-4), RMSE = 52 m/s).

Aged↗

Nonlinear resonant ultrasound spectroscopy (NRUS) applied to damage assessment in bone.

Nonlinear resonant ultrasound spectroscopy (NRUS) is a resonance-based technique exploiting the significant nonlinear behavior of damaged materials. In NRUS, the resonant frequency(ies) of an object is studied as a function of the excitation level. As the excitation level increases, the elastic nonlinearity is manifest by a shift in the resonance frequency. This study shows the feasibility of this technique for application to damage assessment in bone. Two samples of bovine cortical bone were subjected to progressive damage induced by application of mechanical cycling. Before cycling commenced, and at each step in the cycling process, NRUS was applied for damage assessment. For independent assessment of damage, high-energy x-ray computed tomography imaging was performed but was only useful in identifying the prominent cracks. As the integral quantity of damage increased, NRUS revealed a corresponding increase in the nonlinear response. The measured change in nonlinear response is much more sensitive than the change in linear modulus. The results suggest that NRUS could be a potential tool for micro-damage assessment in bone. Further work must be carried out for a better understanding of the physical nature of damaged bone and for the ultimate goal of the challenging in vivo implementation of the technique.

Animals↗

An in vitro study of the ultrasonic axial transmission technique at the radius: 1-MHz velocity measurements are sensitive to both mineralization and intracortical porosity.

UNLABELLED: The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). Using synchrotron radiation microCT, we investigated, in vitro, the relationships between 1-MHz axial transmission SOS measurements at the radius and site-matched measurements of C.Th, POR, MIN, and vBMD. INTRODUCTION: The ultrasonic axial transmission technique allows for investigating skeletal sites such as the cortical layer of long bones (radius, tibia, phalanges). MATERIALS AND METHODS: Using synchrotron radiation microCT, we investigated, in vitro, the relationships between 1-MHz axial transmission speed of sound (SOS) measurements at the radius and site-matched measurements of cortical thickness (C.Th), intracortical porosity (POR), tissue mineralization (MIN), and volumetric BMD (vBMD). SOS measurements were based on bidirectional axial transmission and were performed with a 1-MHz proprietary probe on 39 excised human radii. RESULTS: The highest correlations between SOS values and bone parameters (R(2)(SOS/POR) = 0.28, p < 10(-3); R(2)(SOS/MIN) = 0.38, p < 10(-4); R(2)(SOS/vBMD) = 0.57, p < 10(-3)) were found for bone parameters assessed in a 1-mm-thick periosteal region of the cortex rather than throughout the whole cortex. The observed moderate correlation between SOS and C.Th values (R(2)(SOS/C.Th) = 0.20, p < 10(-2)) disappeared when controlled for other variables. The two best multilinear predictive models, including either BMD alone or the pair of dependent variables MIN and POR (all assessed in the periosteal cortex), were equally accurate in predicting SOS values (R(2)(SOS/(POR,MIN)) = 0.59, p < 10(-5); R(2)(SOS/vBMD) = 0.57, p < 10(-5)). CONCLUSION: For the first time, the respective adjusted contributions of POR (-24 m/s%(-1)) and tissue mineralization (+3.5 m/s/mg/cm(-3)) to SOS values were assessed. These results suggest potential sensitivity of axial transmission SOS values to changes in cortical bone status under different pathological conditions or treatments affecting POR and/or tissue mineralization.

Aged↗

Bidirectional axial transmission can improve accuracy and precision of ultrasonic velocity measurement in cortical bone: a validation on test materials.

The axial transmission technique uses a linear arrangement of ultrasonic emitters and receivers placed on a same side of a cortical bone site in contact with the skin, involving ultrasonic propagation along the axis of bone. The velocity of the waves radiated from bone has been shown to reflect bone status. The thickness and composition of soft tissue may vary along the length of the bone, between different skeletal sites, or between subjects. Hence, accurate estimates of velocity require first to eliminate the effect of the overlying soft tissue that is traversed by the ultrasound wave. To correct for such bias without measuring soft tissue properties, we designed new ultrasonic probes in the 1-2 MHz frequency range. It is based on propagation along the bone surface in two opposite directions from two sources placed on both sides of a unique group of receivers. The aim is to obtain an unbiased estimate of the velocity without any intermediate calculation of soft tissue properties, such as thickness variation or velocity. Validation tests were performed on academic material such as Perspex or aluminum. We found that head wave velocity values could be biased by more than 10% for inclination of a few degrees between the test specimen surface and the probe. On test materials, the compensation procedure implemented in our probe led to a relative precision error on velocity measurement lower than 0.2 to 0.3%. These results suggest that the correction procedure allows measuring in vivo velocities independently of soft tissue properties.

Algorithms↗