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Modality independent elastography (MIE): a new approach to elasticity imaging.

The correlation between tissue stiffness and health is an accepted form of organ disease assessment. As a result, there has been a significant amount of interest in developing methods to image elasticity parameters (i.e., elastography). The modality independent elastography (MIE) method combines a nonlinear optimization framework, computer models of soft-tissue deformation, and standard measures of image similarity to reconstruct elastic property distributions within soft tissue. In this paper, simulation results demonstrate successful elasticity image reconstructions in breast cross-sectional images acquired from magnetic resonance (MR) imaging. Results from phantom experiments illustrate its modality independence by reconstructing elasticity images of the same phantom in both MR and computed tomographic imaging units. Additional results regarding the performance of a new multigrid strategy to MIE and the implementation of a parallel architecture are also presented.

Algorithms↗

A three-parameter mechanical property reconstruction method for MR-based elastic property imaging.

A reconstruction process featuring full parameterization of the three dimensional, time-harmonic equations of linear elasticity is developed and reconstructed property images are presented from simulation-based investigation. While interesting in its own right through the potential for increased adaptability of these reconstructive elastic imaging techniques, this study also presents a set of analysis tools used to study the poor convergence behavior found in the case of tissue like conditions (i.e. nearly incompressible materials). The choice of elastic properties for imaging in elastography research remains an open question at this point; the use of the stability and sensitivity-based analytical methods described here will help to predict and understand the value and reliability of different parameterizations of elasticity imaging. Additionally, though results indicate significant work needs to be done to achieve effective multiparameter reconstructive imaging, the methods detailed here offer the promise of increased flexibility and sophistication in elastographic imaging techniques.

Algorithms↗

The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force.

Several ultrasound-based techniques for the estimation of soft tissue elasticity are currently being investigated. Most of them study the medium response to dynamic excitations. Such responses are usually modeled in a purely elastic medium using a Green's function solution of the motion equation. However, elasticity by itself is not necessarily a discriminant parameter for malignancy diagnosis. Modeling viscous properties of tissues could also be of great interest for tumor characterization. We report in this paper an explicit derivation of the Green's function in a viscous and elastic medium taking into account shear, bulk, and coupling waves. From this theoretical calculation, 3D simulations of mechanical waves in viscoelastic soft tissues are presented. The relevance of the viscoelastic Green's function is validated by comparing simulations with experimental data. The experiments were conducted using the supersonic shear imaging (SSI) technique which dynamically and remotely excites tissues using acoustic radiation force. We show that transient shear waves generated with SSI are modeled very precisely by the Green's function formalism. The combined influences of out-of-plane diffraction, beam shape, and shear viscosity on the shape of transient waves are carefully studied as they represent a major issue in ultrasound-based viscoelasticity imaging techniques.

Acoustics↗

Dynamic mechanical response of elastic spherical inclusions to impulsive acoustic radiation force excitation.

Acoustic radiation force impulse imaging has been used clinically to study the dynamic response of lesions relative to their background material to focused, impulsive acoustic radiation force excitations through the generation of dynamic displacement field images. Dynamic displacement data are typically displayed as a set of parametric images, including displacement immediately after excitation, maximum displacement, time to peak displacement, and recovery time from peak displacement. To date, however, no definitive trends have been established between these parametric images and the tissues' mechanical properties. This work demonstrates that displacement magnitude, time to peak displacement, and recovery time are all inversely related to the Young's modulus in homogeneous elastic media. Experimentally, pulse repetition frequency during displacement tracking limits stiffness resolution using the time to peak displacement parameter. The excitation pulse duration also impacts the time to peak parameter, with longer pulses reducing the inertial effects present during impulsive excitations. Material density affects tissue dynamics, but is not expected to play a significant role in biological tissues. The presence of an elastic spherical inclusion in the imaged medium significantly alters the tissue dynamics in response to impulsive, focused acoustic radiation force excitations. Times to peak displacement for excitations within and outside an elastic inclusion are still indicative of local material stiffness; however, recovery times are altered due to the reflection and transmission of shear waves at the inclusion boundaries. These shear wave interactions cause stiffer inclusions to appear to be displaced longer than the more compliant background material. The magnitude of shear waves reflected at elastic lesion boundaries is dependent on the stiffness contrast between the inclusion and the background material, and the stiffness and size of the inclusion dictate when shear wave reflections within the lesion will interfere with one another. Jitter and bias associated with the ultrasonic displacement tracking also impact the estimation of a tissue's dynamic response to acoustic radiation force excitation.

Acoustics↗

Degree of ultraviolet-induced tortuosity of elastic fibers in rat skin is age dependent.

To elucidate differential effects of ultraviolet (UV) exposure on three-dimensional networks of elastic fibers during maturation of rat skin, Sprague-Dawley rat hind limbs were irradiated with suberythemal doses of UV light (UVB, 130 mJ/cm2, or UVA, 27 J/cm2) in three different time courses of exposure: 3-9 weeks old, 9-15 weeks old, and 3-15 weeks old. Three-dimensional arrangement with special reference to linearity of elastic fibers was quantified by image analysis using a scanning electron microscope after a combination of intravascular resin injection and selective digestion technique using formic acid. Among the three irradiation groups, the group irradiated with UVB or UVA between 3 and 15 weeks old (UVB, three times per week; UVA, five times per week) elicited the most marked decrease in the linearity of elastic fibers. Despite the same irradiation period, there was a significant difference in the decreased linearity between the two irradiation groups of 3-9 and 9-15 weeks old, with the former irradiation group exhibiting greater loss of linearity than the latter irradiation group. The magnitude of the decreased linearity was greater in the UVB-exposed groups than in the UVA-exposed group. These findings indicate that the three-dimensional linearity of elastic fibers is more susceptible to disruption by UV exposures during the growth period than that after the growth period.

Aging↗

Oxytalan, elaunin, and elastic fibers in the human skin.

The elastic system of normal human skin was studied by light and electron microscopy. By light microscopy three different types of fibers were observed: oxytalan, elaunin, and elastic. The most superficial ones (oxytalan fibers) are very thin and directed perpendicularly to the dermoepidermal junction. They start from a plexus with the tinctorial characteristics of elaunin fibers which is connected with the thicker elastic fibers of the reticular dermis. At the electron microscopic level the oxytalan fibers are formed by bundles of tubular microfibrils 10 to 12 nm in diameter. In the deepest layers of the dermis an amorphous material is seen in the core of these bundles. In the elaunin fibers the amorphous material is sparse, while in the elastic fibers it is abundant and compact.

Adolescent↗

Elastic fibers in fetal dermis.

Dermal elastic tissue in fetal skin was evaluated by light microscopy using three different staining techniques. Postmortem skin was obtained from the abdominal wall of 45 fetuses ranging in age from 8 to 42 weeks. Elastic fibers were first detected in skin from fetuses of 22 weeks and, with increasing gestational age, appeared to increase in quantity and complexity. Skin from fetuses older than 32 weeks had a well-developed network of elastic fibers throughout the dermis. There was no diminution of dermal elastic tissue during the latter part of the sixth lunar month as had been reported in a previous study.

Body Weight↗

Pulmonary elastic tissue in generalized elastolysis (cutis laxa) and Marfan's syndrome: a light and electron microscopic study.

We have studied elastic tissue changes in the lungs from patients with Marfan's syndrome, generalized elastolysis, patients with emphysema of other cause, and those dying from unrelated causes. Degenerative changes were seen in the elastic tissue fibers in patient's with Marfan's syndrome; they varied from mild to severe. Elastic fibers in the lungs of patients with cutis laxa showed by light and electron microscopy the same morphologic changes previously reported in the skin and vessels. While the alterations in individual elastic fibers in the alveolar septa appeared similar, in cutix laxa there was severe involvement of almost all fibers, whereas in Marfan's syndrome the involvement was not so severe, nor did it affect all fibers. On examination of lung sections from patients with cutis laxa or Marfan's syndrome, both were readily separable from normal and abnormal controls.

Adult↗

Immunohistochemical demonstration of age-related deposition of vitronectin (S-protein of complement) and terminal complement complex on dermal elastic fibers.

Immunoreactivity of vitronectin was investigated in 100 skin specimens from different body regions in 87 individuals of different ages using monoclonal and polyclonal anti-vitronectin antibodies in an avidin-biotin-peroxidase complex technique. Vitronectin immunoreactivity was found in conjunction with dermal elastic fibers in all subjects older than 13 years. No vitronectin immunostaining was detected in subjects younger than six years, suggesting deposition of vitronectin during late childhood or early adolescence. Using an immunogold staining procedure, vitronectin immunoreactivity was ultrastructurally localized to the periphery of elastic fibers. The blood level of vitronectin in 20 healthy newborns was 67% of the adult level, suggesting active biosynthesis already in the fetus. To investigate whether vitronectin is deposited as part of the SC5b-9 complex or as uncomplexed protein, the immunoreactivity of vitronectin was compared with that of C9, using monoclonal and polyclonal antibodies against the C9 neoantigen. Distinct C9 neoantigen immunoreactivity was demonstrated in association with dermal elastic fibers in human skin in adults but only in subjects older than 30 years. The intensity of C9 neoantigen immunoreactivity appeared to increase with age and was found to be stronger in sun-exposed skin than in sun-protected skin. These findings indicate that uncomplexed vitronectin is deposited during childhood or early adolescence and that terminal complement complexes (C5b-9 and/or SC5b-9) are deposited on elastic fibers later on in life. Hypothetically, the tissue form of vitronectin may be involved in the prevention of tissue damage in proximity to local complement activation. In addition, it may be physiologically important as substratum for cells, stimulating cell migration and anchorage.

Adolescent↗

Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology.

Deficiency of the extracellular matrix protein tenascin-X (TNX) was recently described as the molecular basis of a new, recessive type of Ehlers-Danlos syndrome. Here we report gross abnormalities of the elastic fibers and microfibrils in the dermis of these patients, and reduced dermal collagen content, as determined by quantitative image analysis. The ascending, fine elastic fibers in the papillary dermis were absent or inconspicuous and had few branches. The coarse elastic fibers of the reticular dermis were fragmented and clumped. At the ultrastructural level, irregular and immature elastin fibers and fibers devoid of microfibrils were observed. In TNX-deficient patients the dermal collagen density was reduced, but no structural abnormalities in the collagen fibrils were found. These findings suggest that both elastic fiber abnormalities and reduced collagen content contribute to the observed phenotype in TNX-deficient patients.

Adult↗

Measurement of skin elastic properties with a new suction device (II): systemic sclerosis.

We previously reported the skin elastic properties of normal subjects as measured by a newly developed suction device (6). In the present report, we examined the skin elastic properties of 62 patients with systemic sclerosis (SSc), clinically diagnosed as limited or diffuse type. We measured the skin elastic properties on the forearm and chest and investigated correlations with disease type and clinical skin score. Patients with the diffuse type SSc showed significantly lower values than those with the limited type SSc or normal subjects in distention and retraction ability at the chest and forearm. This suction device is clinically useful for the objective evaluation of skin elastic properties in diffuse systemic sclerosis.

Adult↗

Transepithelial elimination of elastic fibres in the regenerated human epidermis.

The elimination of elastic fibres through the regenerated epidermis of human skin was studied using histochemical, immunofluorescent and electron microscopic techniques. No abnormality was detected in the elastic fibres which were being eliminated, but they were in direct contact with the cytomembranes of some lymphocytes and were captured by histiocytes. It seemed that these elastic fibres were recognized as a foreign substance and provoked inflammation. Lymphocytes and histiocytes may play an important role in the transepithelial elimination of elastic fibres.

Adult↗

Elastic fibres in normal and sun-damaged skin: an immunohistochemical study.

Sun-exposed and sun-protected skin obtained at post mortem from the nape of the neck in 14 subjects was immunostained using antisera to elastin, lysozyme, amyloid P component, and the plasma protease inhibitors alpha-I antitrypsin, alpha-I antichymotrypsin and alpha-2 macroglobulin. Both the normal elastic fibres in sun-protected skin, and elastosis in sun-exposed skin were positively immunostained for elastin, lysozyme and amyloid P component. Collagen fibres were unstained. No immunostaining of normal elastic fibres or elastosis in the skin was obtained with antisera to alpha-I antitrypsin, alpha-I antichymotrypsin or alpha-2 macroglobulin. It was concluded that the elastosis in sun-exposed skin does contain elastic fibres. The absence of immunostaining for plasma protease inhibitors probably indicates that the elastic material is mature, and not newly-formed.

Elastic Tissue↗

Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers.

Biopsies were taken from the upper and inner arm of 10 60-year-old male cigarette smokers and compared with 10 age-matched controls who were non-smokers. The mean relative area, number and thickness of the elastic fibres were significantly increased in the cigarette smokers compared to the controls. These results were confirmed using antibodies to elastin or the microfibrillar component of elastic tissue. In the smokers the broader and more fragmented elastic fibres in the skin were not as intensely stained as those of the non-smokers and the ultrastructural alterations of the elastic fibres were similar to those in solar elastosis.

Antibodies↗

Structure-staining relationships in histochemistry and biological staining. II. Mechanistic and practical aspects of the staining of elastic fibres.

Correlations between the structural features of dyes and staining performance for elastic fibres were investigated. Dyes studied included the traditional stains (such as Gomori's Aldehyde-Fuchsin and Weigert's Resorcin-Fuchsin), acid dyes used from alkaline aqueous-organic solvent mixtures (the Horobin-James system), and basic dyes used from acidic aqueous-ethanolic mixtures (the Taenzer-Unna system). In all three classes effective elastic fibre stains had large conjugated bond numbers, and were often hydrophobic (i.e. had high Hansch pi values). By choosing dyes with conjugated bond numbers at or over a critical value (25 for the TU system, 35 for the HJ) it is possible to select new and effective dyes for use in the HJ and TU staining systems. Mechanistically these results support the view that for typical commercial dyes and also for the traditional stains van der Waals attractions provide the important contributions to dye-elastic fibre affinities, with hydrophobic bonding playing a subsidiary role. However, supporting the views of Lillie, it was also noted that even hydrophilic dyes of low conjugated bond number could stain elastic fibres, if the dye carried a sufficiently reactive primary amino group as a substituent. The additional substituent groupings needed to generate such reactivity have been specified, for both acidic and alkaline reaction conditions.

Animals↗

The determination of elastic recovery of impression materials at the setting time.

One of the prime requisites of an elastomeric impression material is that it should possess adequate elastic recovery on removal from undercut areas. Most standard methods of measuring elastic recovery rely on the preparation of specimens in moulds. The specimens are subsequently removed and subjected to compressive or tensile stresses several minutes after the setting time. The equipment described in this paper has been developed to enable elastic recovery values to be determined at times in the vicinity of the setting time. A shear strain is induced in the material for a short time and the resulting recovery recorded graphically. Results indicate that there is a significant improvement in elastic recovery from just prior to until just after the setting time.

Chemical Phenomena↗

Fine structure alterations of elastic fibers in pseudoxanthoma elasticum.

Examination by electron microscopy of the elastic fibers of individuals with Pseudoxanthoma Elasticum (PXE) revealed that the principal alterations were in the elastin moiety of the elastic fibers. The elastin had a granular appearance, an increased affinity for cationic stains, and it often demonstrated sites of increased density presumed to represent foci of calcification. In contrast to the elastin, the microfibrillar component of the elastic fibers was unchanged, both in morphologic appearance and in distribution. There was no clear correlation between the extent of the morphologic alteration in the elastic fiber and the level of clinical severity. Morphologically altered fibers were often found together with unaltered fibers. Changes similar to those seen in patients with PXE were also found in biopsies obtained from clinically unaffected consanguinous relatives. The pattern of inheritance in several of the families examined was compatible with autosomal recessive, whereas in at least one family a more complex mode of transmission seems likely. The electron microscopic data therefore provide further support for the genetic heterogeneity of PXE.

Adolescent↗

Quantification by image analysis of the Gallus gallus lung elastic fibres from embryonic to adult birds.

The organization of the lung's elastic fibres is amazingly uniform in all vertebrates, with the possible exception of birds, whose pulmonary architecture and air movement are unique. The overall goal of this work was to study and quantify elastic fibre distribution patterns and relative amounts in the parabronchi, during the incubation period until the 42nd day after hatching. Chick embryo lungs were examined on the 14th, 16th, 18th and 20th days of incubation and chick lungs on the 1st, 2nd, 7th, 14th, 35th and 42nd days after hatching. Four animals were used daily, and the observations were randomly performed on both lungs. A morphometric study was carried out focusing on the computerized image analysis of histological sections stained according to a modified Gomori technique. The values obtained for each day result from the observation and processing of 20 images. Complementary studies were performed using transmission electron microscopy, as on the 14th embryonic day the fibres were not visible on light microscopy. The results show that the area occupied by the elastic fibres increases gradually from the 16th day of incubation up till the 7th day after hatching and decreases slowly in the following days of the study. A prominent increase takes place before hatching, which points out to the adequate and essential structural roles played by the elastic fibres in the pulmonary maturation process.

Aging↗