The simulation of magnetic resonance elastography through atherosclerosis.

The clinical diagnosis of atherosclerosis via the measurement of stenosis size is widely acknowledged as an imperfect criterion. The vulnerability of an atherosclerotic plaque to rupture is associated with its mechanical properties. The potential to image these mechanical properties using magnetic resonance elastography (MRE) was investigated through synthetic datasets. An image of the steady state wave propagation, equivalent to the first harmonic, can be extracted directly from finite element analysis. Inversion of this displacement data yields a map of the shear modulus, known as an elastogram. The variation of plaque composition, stenosis size, Gaussian noise, filter thresholds and excitation frequency were explored. A decreasing mean shear modulus with an increasing lipid composition was identified through all stenosis sizes. However the inversion algorithm showed sensitivity to parameter variation leading to artefacts which disrupted both the elastograms and quantitative trends. As noise was increased up to a realistic level, the contrast was maintained between the fully fibrous and lipid plaques but lost between the interim compositions. Although incorporating a Butterworth filter improved the performance of the algorithm, restrictive filter thresholds resulted in a reduction of the sensitivity of the algorithm to composition and noise variation. Increasing the excitation frequency improved the techniques ability to image the magnitude of the shear modulus and identify a contrast between compositions. In conclusion, whilst the technique has the potential to image the shear modulus of atherosclerotic plaques, future research will require the integration of a heterogeneous inversion algorithm.

Viscoelasticity-based magnetic resonance elastography for the assessment of liver fibrosis in hepatitis C patients after liver transplantation.

PURPOSE: Despite advantages in antiviral therapy of hepatitis C (HCV) in recent years, progressing liver fibrosis remains a major problem for patients suffering from hepatitis C after liver transplantation. Therefore, effective non-invasive methods for the assessment of liver fibrosis are needed in order to guide treatment decisions and predict prognosis in these patients. The aim of this study was to prospectively assess the diagnostic accuracy of viscoelasticity-based magnetic resonance (MR) elastography for the assessment of liver fibrosis in HCV patients after liver transplantation. MATERIALS AND METHODS: After IRB approval, a total of 25 patients, who had received a liver graft due to chronic hepatitis C underwent both liver biopsy and MR elastography. Two viscoelastic constants, the shear elasticity µ and the powerlaw exponent α were calculated by fitting the frequency function of the complex shear modulus with the viscoelastic springpot-model. RESULTS: A strong positive correlation between shear elasticity µ and the stage of fibrosis could be found (R = 0.486, p = 0.0136). The area under the receiver operating curve (AUROC) of MR elastography based on µ for diagnosis of severe fibrosis (F ≥ 3) was 0.87 and 0.65 for diagnosis of significant fibrosis (F ≥ 2). The powerlaw exponent α did not correlate with the stage of fibrosis. CONCLUSION: MR elastography represents a promising non-invasive procedure for the assessment of higher grades of fibrosis in HCV patients after liver transplantation. The poor correlation for lower grades of fibrosis suggests unknown mechanical interactions in the transplanted liver.

[Assessment of the solid-liquid behavior of the liver for the diagnosis of diffuse disease using magnetic resonance elastography]. / Untersuchung des Fest-flüssig-Materialverhaltens der Leber zur nicht invasiven Diagnose diffuser Lebererkrankungen mittels Magnetresonanz-Elastografie.

PURPOSE: Recent magnetic resonance elastography (MRE) studies have reported the potential of this noninvasive method for diagnosing hepatic fibrosis based on the elastic properties of liver tissue. However, in many cases biological tissue responds to mechanical vibrations as a combined solid-liquid body causing MRE-derived elastic parameters to become functions of the applied vibration frequency. Therefore a multi-frequency MRE study of liver was performed and the potential of the method for separating healthy from fibrotic liver was investigated. The aim of this study was the increase of the accuracy of liver elastography by analyzing multi-frequency MRE examinations using the springpot model. MATERIALS AND METHODS: 18 healthy volunteers and 10 patients were examined by multi-frequency MRE of the liver in a frequency range between 25 Hz and 62.5 Hz. The liver was mechanically excited with four harmonic vibrations simultaneously. The measured dispersion of the complex modulus was analyzed using the springpot model which accounts for both elastic and viscous properties of a material with 2 independent parameters. RESULTS: The mechanical stimulation and the motion encoding according to the multi-frequency approach was implemented successfully. Significant differences (p < 0.05) were found in the hepatic viscoelasticities of normal livers. The separation of healthy volunteers and patients was achieved with a sensitivity and specificity of 80 and 100 %, respectively. CONCLUSION: Using the springpot model, multi-frequency MRE is sensitive to interindividual differences in the hepatic viscoelastic properties of healthy volunteers. The obtained accuracy of the technique in separating healthy from fibrotic livers opens the possibility of applying multi-frequency MRE as a noninvasive method for diagnosing liver fibrosis in the future.

Three-dimensional analysis of shear wave propagation observed by in vivo magnetic resonance elastography of the brain.

Dynamic magnetic resonance elastography (MRE) is a non-invasive method for the quantitative determination of the mechanical properties of soft tissues in vivo. In MRE, shear waves are generated in the tissue and visualized using phase-sensitive MR imaging methods. The resulting two-dimensional (2-D) wave images can reveal in-plane elastic properties when possible geometrical biases of the wave patterns are taken into account. In this study, 3-D MRE experiments of in vivo human brain are analyzed to gain knowledge about the direction of wave propagation and to deduce in-plane elastic properties. The direction of wave propagation was determined using a new algorithm which identifies minimal wave velocities along rays from the surface into the brain. It was possible to quantify biases of the elastic parameters due to projections onto coronal, sagittal and transversal image planes in 2-D MRE. It was found that the in-plane shear modulus is increasingly overestimated when the image slice is displaced from narrow slabs of 2-5cm through the center of the brain. The mean shear modulus of the brain was deduced from 4-D wave data with about 3.5kPa. Using the proposed slice positions in 2-D MRE, this shear modulus can be reproduced with an acceptable error within a fraction of the full 3-D examination time.

Analysis, synthesis, and perception of voice quality variations among female and male talkers.

Voice quality variations include a set of voicing sound source modifications ranging from laryngealized to normal to breathy phonation. Analysis of reiterant imitations of two sentences by ten female and six male talkers has shown that the potential acoustic cues to this type of voice quality variation include: (1) increases to the relative amplitude of the fundamental frequency component as open quotient increases; (2) increases to the amount of aspiration noise that replaces higher frequency harmonics as the arytenoids become more separated; (3) increases to lower formant bandwidths; and (4) introduction of extra pole zeros in the vocal-tract transfer function associated with tracheal coupling. Perceptual validation of the relative importance of these cues for signaling a breathy voice quality has been accomplished using a new voicing source model for synthesis of more natural male and female voices. The new formant synthesizer, KLSYN88, is fully documented here. Results of the perception study indicate that, contrary to previous research which emphasizes the importance of increased amplitude of the fundamental component, aspiration noise is perceptually most important. Without its presence, increases to the fundamental component may induce the sensation of nasality in a high-pitched voice. Further results of the acoustic analysis include the observations that: (1) over the course of a sentence, the acoustic manifestations of breathiness vary considerably--tending to increase for unstressed syllables, in utterance-final syllables, and at the margins of voiceless consonants; (2) on average, females are more breathy than males, but there are very large differences between subjects within each gender; (3) many utterances appear to end in a "breathy-laryngealized" type of vibration; and (4) diplophonic irregularities in the timing of glottal periods occur frequently, especially at the end of an utterance. Diplophonia and other deviations from perfect periodicity may be important aspects of naturalness in synthesis.

The dorsal raphe nucleus: a re-evaluation of its proposed role in opiate analgesia systems.

Previous studies have concluded that (a) electrical stimulation in the periaqueductal gray/dorsal raphe nucleus (PAG/DRN) region specifically produces either non-opiate or opiate forms of antinociception dependent upon the dorsoventral level of stimulation and (b) the 'opiate' form of stimulation-produced analgesia (SPA) arising from the ventral PAG/DRN region shows cross-tolerance with opiate forms of footshock analgesia, implying common neural substrates. This latter conclusion in turn implies that SPA elicited from the ventral PAG/DRN region would be expected to be antagonized by scopolamine, since this muscarinic cholinergic antagonist blocks opiate footshock analgesia. The present study demonstrates instead that neither 10 mg/kg naloxone nor 10 mg/kg scopolamine had any effect on SPA elicited from sites histologically verified to lie within the presumptive 'opiate' ventral PAG/DRN region. These data bring into question both the site specificity of opiate SPA and the common mediation of ventral PAG/DRN SPA and opiate forms of footshock analgesia.

Review of text-to-speech conversion for English.

The automatic conversion of English text to synthetic speech is presently being performed, remarkably well, by a number of laboratory systems and commercial devices. Progress in this area has been made possible by advances in linguistic theory, acoustic-phonetic characterization of English sound patterns, perceptual psychology, mathematical modeling of speech production, structured programming, and computer hardware design. This review traces the early work on the development of speech synthesizers, discovery of minimal acoustic cues for phonetic contrasts, evolution of phonemic rule programs, incorporation of prosodic rules, and formulation of techniques for text analysis. Examples of rules are used liberally to illustrate the state of the art. Many of the examples are taken from Klattalk, a text-to-speech system developed by the author. A number of scientific problems are identified that prevent current systems from achieving the goal of completely human-sounding speech. While the emphasis is on rule programs that drive a format synthesizer, alternatives such as articulatory synthesis and waveform concatenation are also reviewed. An extensive bibliography has been assembled to show both the breadth of synthesis activity and the wealth of phenomena covered by rules in the best of these programs. A recording of selected examples of the historical development of synthetic speech, enclosed as a 33 1/3-rpm record, is described in the Appendix.

Release of microvesicles from erythrocytes during storage in saline-adenine-glucose media.

Storage of human erythrocytes in SAG media results in the release of membrane microvesicles with a diameter of about 190 nm. They can be separated from intact erythrocytes by centrifugation on a dextran barrier solution (density 1.078 g/l). Vesicles prepared from cold stored erythrocyte concentrates are like those released upon ATP depletion by erythrocytes incubated without glucose at 37 degrees C [15]. The course of vesiculation was followed by measuring acetylcholinesterase during storage of the erythrocyte concentrate for 35 days. Its activity remained constant within the storage units during the preservation period. This enzyme and phospholipids were released continuously in a proportional manner. The release of sialic acid amounted to about half of that of phospholipids. Owing to depletion of 2,3-bisphosphoglycerate the binding of ATP to haemoglobin increased and the concentration of free ATP declined. Addition of an ion-exchange resin to stored erythrocytes kept the pH constant, retarded the breakdown of 2,3-P2G and stabilized the concentration of free ATP. That inhibited the rate of irreversible vesiculation. Therefore, maintenance of 2,3-bisphosphoglycerate plus ATP during long-term storage of erythrocytes is a condition of keeping intact their membrane, metabolism and oxygen transport function.

Involvement of polyphosphoinositides in the ATP turnover of intact human erythrocytes and in the ATPase activity of purified membranes.

The phosphorylation cycle of polyphosphoinositides is an important process among the ATP-consuming reactions of human erythrocytes with "low" ATP-affinity. It serves to maintain a high level of PI-4,5-P2 in the membrane.

Membrane phosphorylation in intact human erythrocytes.

The time course of 32P incorporation into ATP and monoesterified membrane phosphatases was studied within 1 h of incubation of intact human erythrocytes. Analysis of membrane proteins and phospholipids showed dynamically exchanged phosphates mainly in the phospholipid fraction. The extent of ATP turnover by spectrin band 2 polypeptide phosphorylation was very small. The 32P-ATP and the membrane 32P-phosphate label could be chased via the metabolism by the addition of extracellular Pi. From the relative changes in the specific radioactivity of ATP and of the membrane phosphate in intact erythrocytes we assume that about 60% of the erythrocyte ATP production are linked to the ATP consumption by the rapid polyphosphoinositide turnover. It is conceivable that there is a connection between the protein factors modifying the affinity of (Ca2+, Mg2+)-ATPase and the metabolism of the polyphosphoinositides in the erythrocyte membrane.

ATP utilizing reactions of human erythrocyte membranes and the influence of modulator proteins.

The ATP production of human erythrocytes in the steady state (approximately 2 mmoles . 1 cells-1 . h-1, 37 degrees C, pHi 7.2) is maintained by glycolysis and the ATP consumption is essentially limited to the cell membrane. About 25% of the ATP consumption is used for ion transport ATPases. The bulk of the ATP consuming processes in intact erythrocytes remains poorly understood. "Isotonic" erythrocyte membranes prepared under approximate intracellular conditions after freeze-thaw hemolysis have high (Ca2+, Mg2+)-ATPase activities (80% of the total membrane ATPase activity). There is a great discrepancy between the high capacity of the (Ca2+, Mg2+)-ATPase in isotonic membranes and the actual activity in the intact cell. The (Ca2+, Mg2+)-ATPase of isotonic membranes has a "high" Ca2+-affinity (Ka less than 0.5 microM) and a "low" Mg-ATP affinity (Km approximately 760 microM). This state of (Ca2+, Mg2+)-ATPase is caused by the association of calmodulin and 30000 Dalton polypeptides (ATP affinity modulator protein). Hypotonic washings of isotonic membranes result in a loss of the 30 kD polypeptides. EGTA (0.5 mM) extracts derived from isotonic membranes contain the 30 kD modulator protein and restore the properties of the (Ca2+, Mg2+)-ATPase of hypotonic membrane preparations to the isotonic characteristics. The Mg-ATP affinity modulator protein is assumed to form a complex with calmodulin and (Ca2+, Mg2+)-ATPase.

The lipoxygenase of reticulocytes. Purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyte.

A lipoxygenase has been purified from rabbit reticulocyte-rich anaemic blood cells. It possesses a molecular weight of 78 000 and an isoelectric point of 5.5 and contains 5% neutral sugars and two iron atoms per enzyme molecule. The lipoxygenase has proved to be identical with the inhibitors of respiratory proteins described formerly. The actions of the lipoxygenase on linoleic acid, phospholipids, mitochondrial and erythrocyte membranes and electron transfer particles were studied. A special feature of the reticulocyte lipoxygenase is the suicidal character of its action on lipids. With electron transfer particles the reticulocyte lipoxygenase causes a loss of acid-labile sulfur which accompanies respiratory inhibition; the strong respiratory inhibition is not exerted by soybean lipoxygenase. The reticulocyte lipoxygenase acts preferably on mitochondrial membranes as compared with cell membranes of the erythrocyte; erythrocyte cytosol moderates the action on mitochondrial membranes. Furthermore, the lipoxygenase reaction can concomitantly and irreversibly inactivate sulfhydryl enzymes as demonstrated with muscle glyceraldehyde-3-phosphate dehydrogenase. The occurrence of the lipoxygenase here described is restricted to reticulocytes; very low amounts were observed in bone marrow and no lipoxygenase was detectable in normal blood. During the course of an experimental anaemia the lipoxygenase is produced owing to superinduction in large amounts, which may persist for a long time since they escape inactivation. Preliminary evidence was obtained for the occurrence of other lipoxygenases in tissues of lung, spleen, kidney and also epithelial tumours.

[Receptors of human red blood cells for anti-TAH and anti-AHP in the course of intravascular aging]. / Rezeptoren roter Blutzellen des Menschen für Anti-TAH und Anti-AHP beim intravasalen Altern der Zellen.

Human o-erythrocytes aged in situ do not expose free receptors for anti-T agglutinin of Arachis hypogea. New receptors for concentrated anti-A agglutinin of Helix pomatia are manifested but are lost again in the course of further ageing of the cells in situ. A remasking of exposed receptors for anti-TAH and anti-AHP byautologous, strongly binding globulins is supposed. These globulins could constitute the decisive signal for the autologous phagocytosis of senescent red blood cells.

Mechanism of senescence of red blood cells.

An integral hypothesis is submitted on the interaction of endogenous and exogenous factors in the mechanism of senescence of erythrocytes and on their selective phagocytosis by autologous macrophages. A method that allows quantitative determination and preparative yield of senescent erythrocytes is proposed.

Voice onset time, frication, and aspiration in word-initial consonant clusters.

The voice onset time (VOT) and the duration of the burst of frication noise at the release of a plosive consonant were measured from spectrograms of word-initial consonant clusters. Mean data from three speakers reading English words in a sentence frame indicated that the VOT changed as a function of the place of articulation of the plosive and as a function of the identity of the following vowel or sonorant consonant. Burst durations varied in a similar way such that the remaining interval of aspiration in /p, t, k/ was nearly the same duration in comparable phonetic environments. The VOT was longer before sonorants and high vowels than before mid- and low vowels. Aspiration was also seen in an /s/-sonorant cluster. To explain these regularities, production strategies and perceptual cues to a voicing decision for English plosives are considered. Variations in VOT are explained in terms of articulatory mechanisms, perceptual constraints, and phonological rules. Some VOT data obtained from a connected discourse were also analyzed and organized into a set of rules for predicting voice onset time in any sentence context.