Elasticity Maps Research Articles

Magnetic Resonance Elastography for the Noninvasive Staging of Liver Fibrosis

The purpose of our study was to prospectively compare the success rate and diagnostic accuracy of magnetic resonance elastography, ultrasound elastography, and aspartate aminotransferase to platelets ratio index (APRI) measurements for the noninvasive staging of fibrosis in patients with chronic liver disease. We performed a prospective blind comparison of magnetic resonance elastography, ultrasound elastography, and APRI in a consecutive series of patients who underwent liver biopsy for chronic liver disease in a university-based hospital. Histopathologic staging of liver fibrosis according to the METAVIR scoring system served as the reference. A total of 141 patients were assessed. The technical success rate of magnetic resonance elastography was higher than that of ultrasound elastography (133/141 [94%] vs 118/141 [84%]; P = .016). Magnetic and ultrasound elastography, APRI measurements, and histopathologic analysis of liver biopsy specimens were technically successful in 96 patients. The areas under the receiver operating characteristic curves of magnetic resonance elasticity (0.994 for F >or= 2; 0.985 for F >or= 3; 0.998 for F = 4) were larger (P < .05) than those of ultrasound elasticity, APRI, and the combination of ultrasound elasticity and APRI (0.837, 0.709, and 0.849 for F >or= 2; 0.906, 0.816, and 0.936 for F >or= 3; 0.930, 0.820, and 0.944 for F = 4, respectively). Magnetic resonance elastography has a higher technical success rate than ultrasound elastography and a better diagnostic accuracy than ultrasound elastography and APRI for staging liver fibrosis.

Elasticity Imaging Using Conventional and High-Frame Rate Ultrasound Imaging: Experimental Study

High-frame rate ultrasound imaging is necessary to track fast deformation in ultrasound elasticity imaging, but the image quality may be degraded. Previously, we investigated the performance of strain imaging using numerical models of conventional and ultrafast ultrasound imaging techniques. In this paper, we performed experimental studies to quantitatively evaluate the strain images and elasticity maps obtained using conventional and high frame rate ultrasound imaging methods. The experiments were carried out using point target and tissue mimicking phantoms. The experimental results were compared with the results of numerical simulation. Our experimental studies confirm that the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and axial/lateral resolution of the displacement and strain images acquired using high-frame rate ultrasound imaging are slightly lower but comparable with those obtained using conventional imaging. Furthermore, the quality of elasticity images also exhibits similar trends. Thus, high-frame rate ultrasound imaging can be used reliably for static elasticity imaging to capture the internal tissue motion if the frame rate is critical.

Noninvasive Vascular Elastography: Toward A Complementary Characterization Tool of Atherosclerosis in Carotid Arteries

Only a minority of patients with carotid arterial disease have warning symptoms, because the majority of strokes are caused by previously asymptomatic lesions. Because morbidity and mortality after acute stroke are high, patients should be diagnosed and treated before symptoms develop. The hypothesis of this study is that vascular elasticity maps (or elastograms) of carotids are of predictive value for plaque characterization. The strain tensor from either cross-sectional or longitudinal ultrasound radiofrequency data were assessed by a new implementation of the Lagrangian speckle model estimator (LSME), which considers local echogenicity variations. A 26-year-old healthy male (HS1), a 40-year-old (HS2) normal female subject and two 75-year-old asymptomatic patients with severe carotid stenoses were scanned. Reproducible elastograms were obtained as a function of time over five to seven cardiac cycles. Stress-strain modulus elastograms were computed for normal subjects. Stiffening of healthy carotid walls was estimated to be 148 ± 7 kPa and 163 ± 30 kPa at peak-systole for HS1 and HS2, respectively. For patients with heterogeneous plaques, strain and shear elastograms revealed interesting information about plaque size, tissue composition and mechanical interaction between structures. In conclusion, the LSME provides a promising approach for strain and shear estimates to characterize vulnerable plaque. (E-mail: guy.cloutier@umontreal.ca)

New developments in transient elastography

An ultra-high-rate ultrasonic scanner has been developed that can give 5000 ultrasonic images per second of the body. With such a high frame rate, the propagation of transient shear waves can be followed, and from the spatio-temporal evolution of the displacement fields, various inversion algorithms allow us to recover the shear modulus map. A discussion on the various inversion algorithms will be presented. In order to obtain unbiased shear elasticity map, different configurations of shear sources induced by radiation pressure of focused transducer arrays are used. Both 2-D and 3-D imaging can obtained with this technique. In vitro and in vivo results on breast will be presented that demonstrate the interest of elasticity imaging with transient elastography.

Liver fibrosis: non‐invasive assessment with MR elastography

The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis. Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study. The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0, no fibrosis, to F4, cirrhosis. MR elastography was performed by transmitting low-frequency (65 Hz) mechanical waves into the liver with a transducer placed at the back of the patients. The MR pulse sequence was a motion-sensitized spin-echo sequence, phase-locked to the mechanical excitation. The phase maps were processed to obtain shear elasticity and shear viscosity maps. The mean hepatic shear elasticity increased with increasing stage of fibrosis. The mean elasticity was 2.24 +/- 0.23 kPa in the 11 patients without substantial fibrosis (F0-F1 grades), 2.56 +/- 0.24 kPa in the four patients with substantial fibrosis (F2-F3) and 4.68 +/- 1.61 kPa in the 10 patients with cirrhosis (F4). The differences between groups were statistically significant (p <or= 0.05). The mean shear viscosity was significantly higher in the patients with cirrhosis (5.19 +/- 1.85 Pa x s) than in the patients without cirrhosis (2.39 +/- 0.86 Pa x s in F0-F1 and 2.27 +/- 0.38 Pa x s in F2-F3 patients). It is concluded that non-invasive MR elastography is a feasible method to assess the stage of liver fibrosis.

Magnetic Resonance Elastography of the Plantar Fat Pads

To test the feasibility of applying the magnetic resonance elastography (MRE) technique to map the elastic modulus of the plantar fat pads in diabetic and nondiabetic subjects. A prototype MRE imaging apparatus was used to produce quantitative maps of the heel fat pad in a pilot study of 12 volunteers and 4 patients with diabetes with neuropathy. Anatomic images corresponding to MRE maps allowed precise selection of regions of interest in the fat. Magnetic resonance elastograms of the heel fat pads were successfully created; mean measurements in the volunteers and the diabetic patients were 4.85 and 5.26 kPa, respectively. It is feasible to perform MRE on the plantar fat pads and to produce elasticity maps. The trend toward stiffer fat pads, as demonstrated in patients with diabetes, suggests that the fat pads were qualitatively different. Magnetic resonance elastography offers great potential to investigate the mechanical properties of soft tissues in vivo noninvasively.

Microscopic dynamic magnetic resonance elastography

Microscopic magnetic resonance elastography (uMRE) is a high resolution imaging technique for measuring the viscoelastic properties of small synthetic and biological samples. Mechanical shear waves, typically with amplitudes of less than 100 μm and frequencies of 500–600 Hz, are induced using a piezoelectric oscillator directly coupled to the region of interest. By using multiple phase offsets and motion encoding gradients we acquire data that allows the generation of images that depict shear wave motion and the calculation of local values of the tissue viscoelastic properties. Recent MRE investigations are increasingly being conducted at higher spatial resolution to establish histological correlations between elasticity maps and tissue structures; such microscopic MRE studies require stronger static fields, stronger magnetic field gradients, higher performance RF coils, and more compact, higher frequency mechanical actuators. Microscopic MRE experiments were conducted at 11.74 T in a 54 mm diameter vertical bore magnet with a 10 mm diameter×25 mm length cylindrical space available for imaging. The field-of-view ranged from 4 to 14 mm. The study was conducted on agarose gel phantoms of different concentrations ranging from 025%–1% w. Different biological samples, including frog oocytes and tissue engineered constructs, were also tested.

Imaging and elasticity measurements of the sarcolemma of fully differentiated skeletal muscle fibres

This study aimed to describe the three-dimensional structure and the elastic properties of the sarcolemma of adult, fully differentiated, skeletal muscle fibres combining Atomic Force Microscopy (AFM) and optical microscopy. Single fibres were enzymatically dissociated from Flexor Digitorum Brevis of adult mice and were maintained in culture up to 3 weeks. On the sixth day after dissociation, the upper surface of intact fibres, either alive in solution or fixed and kept in solution or fixed and exposed in air, was analysed with AFM. The most prominent features in AFM images were periodic transversal foldings with an interval that corresponded to the sarcomere length. More detailed analysis of the topography profile showed that the depth in the folding decreased with increasing sarcomere length and that the crests of the foldings corresponded to the Z-lines. Minor periodic structures could be detected in the valleys between the major foldings. AFM images also showed deep depressions on the sarcolemma likely corresponding to openings of T tubules and caveolae. Two-dimensional elasticity maps were obtained using AFM as an indenter and showed that the crests of the transversal foldings correspond to higher stiffness regions. This study provides the first complete three-dimensional topography and mechanical characterization of intact, living skeletal muscle fibres and might form the basis for further investigations aimed to compare healthy and dystrophic muscles.

In vivo breast tumor detection using transient elastography

This paper presents first in vivo experiments for breast tumor detection using transient elastography. This technique has been developed for detection and quantitative mapping of hard lesions in soft tissues. It consists in following the propagation inside soft tissues of very low-frequency shear waves (∼ 60 Hz) generated by a vibrating system located at the body surface. Because transient shear waves propagate through the medium in less than 0.1 s, the shear propagation imaging is performed with an ultrafast echographic scanner able to reach frame rates up to 6000 Hz. The local shear wave speed is directly linked to the local shear Young's modulus of the medium. The shear elasticity map of the medium can then be computed using an inversion algorithm. In vivo experiments were conducted on 15 women who had palpable breast lesions. For clinical adaptability reasons, shear waves were generated by the surface of the ultrasound (US) imaging transducer itself, which was linked to a mechanical vibrator. Our preliminary in vivo results demonstrate the clinical applicability of the transient elastography technique for breast lesion detection. (E-mail: michael.tanter@espci.fr)

Imaging of lactic acid bacteria with AFM—elasticity and adhesion maps and their relationship to biological and structural data

The adhesion of lactic acid bacteria to the intestinal epithelium is one of the most important factors determining probiotic ability of a bacterial strain. Studying bacterial adhesion requires knowledge of the structure and properties of the bacterial surface, which can be studied by atomic force microscopy under native conditions. The observation of the surface topography of bacteria from the species Lactobacillus crispatus, L. helveticus and L. johnsonii shows major differences between bacteria having a crystalline-like protein layer as part of the cell wall and those without such layers. Force volume images calculated into elasticity and adhesion force maps of different bacterial strains show that L. crispatus and L. helveticus have a surface with a homogeneous stiffness with no adhesion events. This is most likely caused by the S-layer, which completely covers the surface of the bacteria. We infer that the absence of adhesion peaks is caused by the semi-crystalline character of such protein layers, in agreement with the results obtained from electron microscopy. Analysis of a number of L. johnsonii strains shows that these bacteria have surface properties which strongly differ from the L. crispatus and L. helveticus strains. For L. johnsonii DMS20533 and L. johnsonii ATCC33200 high adhesion forces are observed, which can be related to a surface rich in polysaccharides. L. johnsonii ATCC332 has lower adhesion forces compared to the other two and, furthermore, the surface topography shows depressions. We suppose that this strain has a surface pattern consisting of crystalline-like proteins alternating with polysaccharide-rich domains. The wide variety in surface properties of lactobacilli could well have wide-ranging implications for food processing and for health benefits.

Supersonic imaging of elasticity

This paper shows the new possibilities of supersonic imaging of elasticity. It combines ultra‐high speed ultrasonic imaging of tissues with low frequency supersonic shear sources induced in the body by radiation pressure. We have built an Ultrafast Scanner providing up to 5000 frames/s and using conventional arrays linked to a new beamformer. We will show how this scanner is able to follow in real time tissue displacements induced by the transient propagation of LF shear wave in the human body. From the spatio‐temporal evolution of the displacements, a shear elasticity map is constructed using a local inversion algorithm. In order to obtain unbiased shear elasticity map, different configurations of shear sources induced by radiation pressure of focused transducer arrays are used. A very interesting configuration that induces quasi plane shear waves will be described. It used a shear source that moves at supersonic velocities, and that is created by using a very peculiar beam forming in the transmit mode. ...

Ultrafast imaging of shear waves induced by the acoustic radiation force for elasticity imaging in soft tissues

Shear wave propagation induced by the acoustic radiation force is currently under investigation. In our experiments, an ultrafast scanner is used both to generate and detect shear waves propagation. The scanner is first used to focus, at a chosen location, a high intensity ultrasonic beam. The resulting acoustic radiation force induces in the focal zone a shear source. The system allows us then to apply very high ultrasound frame rates (up to 5000 images/s) in order to image the shear wave propagation, which velocity is linked to local elasticity properties of the medium. The elasticity map is recovered by solving the inverse problem. Actually, the generation of shear displacement requires high level insonifications at the threshold of FDA norms. Thus, the great advantage of such an ultrafast scanner is to recover the complete propagation by generating a unique palpation inside the medium. Measurements have been performed in several soft tissue mimicking phantoms with different elastic properties and in beef muscles. The 3-D finite differences simulations have been used to support our experimental results: the delivered acoustic power and the resulting heating induced by the acoustic focused beam can be estimated and compared with the FDA requirements.

Force Modulation Elasticity Mapping of Plastic-embedded, Thin-sectioned Skeletal Muscle.

We have been researching the capability of atomic force microscopy to reveal nontopographic properties of tissue embedded in plastic and sectioned with standard electron microscopic techniques. We present topography and elasticity maps of plastic-embedded, thin sections of muscle tissue. The images show topography correlated with the normal repeating structure of the sarcomere. Elasticity mapping using force modulation revealed contrast between the actin- and myosin-rich areas. We attribute the observed contrast in elasticity to the difference in local concentrations of biological material in embedding plastic.

Nano- to microscale wear and mechanical characterization using scanning probe microscopy

Scanning probe microscopy (SPM) techniques, specifically so-called atomic force/friction force microscopy (AFM/FFM) are increasingly used for tribological studies of engineering surfaces at scales ranging from atomic and molecular to microscales. AFMs with suitable tips are being used to study microscratching, microwear and nanowear and nano/picoindentation behavior of solid surfaces and thin films. AFMs have also been used for nanofabrication/nanomachining purposes. Scratch and wear properties of a variety of materials have been measured. Mechanisms of material removal on the microscale are studied. Wear precursors can be detected at early stages of wear using localized surface potential measurements. Localized surface elasticity maps of composite materials with penetration depths of less than 100 nm can be obtained. Nanoindentation hardness and Young’s modulus of elasticity can be measured with a depth of indentation as low as 1 nm. Scratching and indentation on the nanoscale are powerful ways to screen for adhesion and resistance to deformation of ultrathin coatings. These studies provide insight into failure mechanisms of materials and thin coatings. Finally, in situ surface characterization of local deformation of materials and thin coatings helps to develop better understanding of failure mechanisms.

Force Modulation Elasticity Mapping of Plastic-embedded, Thin-sectioned Skeletal Muscle

AbstractWe have been researching the capability of atomic force microscopy to reveal nontopographic properties of tissue embedded in plastic and sectioned with standard electron microscopic techniques. We present topography and elasticity maps of plastic-embedded, thin sections of muscle tissue. The images show topography correlated with the normal repeating structure of the sarcomere. Elasticity mapping using force modulation revealed contrast between the actin- and myosin-rich areas. We attribute the observed contrast in elasticity to the difference in local concentrations of biological material in embedding plastic.

The application of the atomic force microscope to studies of medically important protozoan parasites.

Both living and fixed specimens of the medically-important parasitic protozoa, Trypanosoma cruzi, Toxoplasma gondii, Giardia lamblia, Entamoeba histolytica, and Acanthamoeba spp. were studied by atomic force microscopy (AFM). The preparation of fixed specimens was similar to methods used for either scanning or transmission electron microscopy. AFM scanning was performed using both contact and tapping modes. A classical fixation procedure utilizing glutaraldehyde followed by ethanol dehydration was not suitable for all parasite species. AFM images could not be obtained from fixed samples of T. cruzi, T. gondii or E. histolytica. However, excellent topographic images could be obtained from specimens of G. lamblia and Acanthamoeba under identical conditions. Critical point drying permitted AFM imaging of both trypomastigote and epimastigote stages of T. cruzi. Phase imaging of T. cruzi elucidated unique surface details at a level of resolution not visible using any other imaging modalities. AFM elasticity map imaging of T. cruzi-infected and T. gondii-infected cells demonstrated that both parasites were markedly firmer than the surrounding host cell cytoplasm. The parasitophorous vacuole surrounding replicating T. gondii tachyzoites was also visualized by elasticity map imaging. These data suggest that although much remains to be learned about preparing parasitic protozoa for AFM imaging, the technique has the potential of providing unique and important insights into these disease causing organisms.

Drug-Induced Changes of Cytoskeletal Structure and Mechanics in Fibroblasts: An Atomic Force Microscopy Study

The effect of various drugs affecting the integrity of different components of the cytoskeleton on the elasticity of two fibroblast cell lines was investigated by elasticity measurements with an atomic force microscope (AFM). Disaggregation of actin filaments always resulted in a distinct decrease in the cell’s average elastic modulus indicating the crucial importance of the actin network for the mechanical stability of living cells. Disruption or chemical stabilization of microtubules did not affect cell elasticity. For the f-actin-disrupting drugs different mechanisms of drug action were observed. Cytochalasins B and D and Latrunculin A disassembled stress fibers. For Cytochalasin D this was accompanied by an aggregation of actin within the cytosol. Jasplakinolide disaggregated actin filaments but did not disassemble stress fibers. Fibrous structures found in AFM images and elasticity maps of fibroblasts could be identified as stress fibers by correlation of AFM data and fluorescence images.

Quantitative analyses of topography and elasticity of living and fixed astrocytes

The topography and elasticity of living and fixed astrocytes cultured from the rat cerebra were studied quantitatively by atomic force microscopy (AFM). Ridge-like structures reflecting F-actin beneath the cell membrane were prominent in the contact-mode images of living astrocytes. Many of these ridges became unclear after fixation (2% glutaraldehyde). In addition, the ridge-like structures were invisible in the topography of living cells observed at zero-loading force in the force mapping mode, which is considered to show the real cell surface not pressed down by an AFM tip. The topography of fixed cells observed both in the contact mode and at zero-loading force in the force mapping mode was similar to that of living cells observed at zero-loading force in the force mapping mode, although some deformed areas were detected in the fixed cells. The elasticity map images of living astrocytes showed that the cell membrane above the nucleus was softer (2-3 kPa) than the surroundings, and that the cell membrane above F-actin was stiffer (10-20 kPa) than the surroundings. In the elasticity map images of fixed astrocytes, on the other hand, the elasticity of the cells was found to be relatively uniform (200-700 kPa) irrespective of the inner structures of cells. These results show that images observed by AFM should be carefully examined in consideration of the force introduced to specimens and the elasticity of specimens to find out the real surface topography.

Wear and mechanical characterisation on micro- to picoscales using AFM

Atomic force/friction force microscopy (AFM/FFM) techniques are increasingly used for tribological studies of engineering surfaces at scales ranging from atomic and molecular to microscales. An AFM with a suitable diamond tip can be used to measure microscratching/microwear and nano-/picoindentation behaviour of solid surfaces and thin films. AFM has also been used for nanofabrication/nanomachining purposes. Scratch and wear properties of a variety of materials have been measured. Mechanisms of material removal on microscales are studied. Wear precursors can be detected at early stages of wear using localised surface potential measurements. Localised surface elasticity maps of composite materials with penetration depths of less than 100 nm can be obtained. Nanoindentation hardness and Young's modulus of elasticity can be measured with a depth of indentation as low as 1 nm. Scratching and indentation on nanoscales are the powerful ways to screen for adhesion and resistance to deformation of ultrathin films. These studies provide insight into failure mechanisms of materials and thin films. Furthermore, in situ surface characterisation of local deformation of materials helps to develop better understanding of fracture mechanisms and the brittle to ductile transition in materials. These studies are directly applicable to interfacial phenomena of microdevices and magnetic storage devices.

Relative Microelastic Mapping of Living Cells by Atomic Force Microscopy

The spatial and temporal changes of the mechanical properties of living cells reflect complex underlying physiological processes. Following these changes should provide valuable insight into the biological importance of cellular mechanics and their regulation. The tip of an atomic force microscope (AFM) can be used to indent soft samples, and the force versus indentation measurement provides information about the local viscoelasticity. By collecting force-distance curves on a time scale where viscous contributions are small, the forces measured are dominated by the elastic properties of the sample. We have developed an experimental approach, using atomic force microscopy, called force integration to equal limits (FIEL) mapping, to produce robust, internally quantitative maps of relative elasticity. FIEL mapping has the advantage of essentially being independent of the tip-sample contact point and the cantilever spring constant. FIEL maps of living Madine-Darby canine kidney (MDCK) cells show that elasticity is uncoupled from topography and reveal a number of unexpected features. These results present a mode of high-resolution visualization in which the contrast is based on the mechanical properties of the sample.