Differentiation between acutely ischemic myocardium and zones of completed infarction in dogs on the basis of frequency-dependent backscatter

The goal of this work was to determine whether the frequency dependence of apparent backscatter coefficient (not corrected for attenuation within the myocardium) could differentiate completed, remote infarction from acute myocardial injury in vivo. Myocardial infarcts were produced in six dogs by coronary artery occlusion. One to 12 months later, acute ischemic injury was induced in each dog by ligation of a coronary artery that supplied a region of myocardium adjacent to the established infarct. Infarct, ischemic, and normal regions were interrogated with a 5-MHz, circular, 0.5-in. diam, broadband, focused, piezoelectric transducer mounted in a water-filled stand-off device placed against the exposed, beating heart. Apparent backscatter coefficients were measured over the range of frequencies from 3-7 MHz. The frequency dependence was obtained from the slope of log apparent backscatter coefficient versus log frequency. No significant difference in frequency dependence was found between normal and acutely ischemic myocardium for periods of up to 2 h of ischemia. In contrast, frequency dependence in regions of remote infarct (1.8 +/- 0.1, mean +/- standard error) was significantly lower than that in acutely ischemic or nonischemic regions (2.3 +/- 0.1) (p less than 0.01). These results suggest that remote myocardial infarction can be differentiated from acutely injured but still potentially salvageable myocardium in vivo on the basis of the frequency dependence of backscatter.     

Contraction-related variation in frequency dependence of acoustic properties of canine myocardium

Results of experiments performed in several laboratories indicate that contracting myocardium exhibits a cyclic variation of the magnitude of ultrasonic backscatter, with maxima occurring at end-diastole and minima at end-systole. The mechanisms responsible for this variation are not well understood. The purpose of the present study was to determine whether the frequency dependence of backscatter exhibits systematic variation throughout the cardiac cycle, analysis of which may facilitate improved understanding of biologic factors responsible for the cyclic variation of the magnitude of backscatter. In this study, the myocardial backscatter coefficient, as a function of frequency, was measured throughout the cardiac cycle in nine open-chest dogs. The frequency dependence of the backscatter coefficient was computed from a least-squares linear fit to log backscatter coefficient versus log frequency data. A cyclic variation of frequency dependence of backscatter was found with maximum near end-diastole (f2.6 +/- 0.1) and minimum near end-systole (f2.2 +/- 0.1), a significant variation (p less than 0.01). These results suggest that mechanisms responsible for the cyclic variation of backscatter may include changes in the effective size of the dominant scatterers throughout the cardiac cycle. An alternative explanation for the observed variation is an increase in the myocardial attenuation coefficient during systole followed by a decrease in diastole.     

The extracellular matrix is an important source of ultrasound backscatter from myocardium

Ultrasound tissue characterization with measurement of backscatter has been employed in numerous experimental and clinical studies of cardiac pathology, yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified. This laboratory has proposed a mathematical model for myocardial backscatter that postulates the fibrous extracellular matrix (ECM) as a significant determinant of backscatter. To demonstrate the importance of ECM, this group sought to determine whether measurements of backscatter from the isolated ECM could reproduce the known directional dependence, or anisotropy of backscatter, from intact cardiac tissues in vitro. Segments of left ventricular free wall from ten formalin fixed porcine hearts were insonified at 50 MHz, traversing the heart wall from endo- to epicardium to measure the anisotropy of myocardial backscatter, defined as the difference between peak (perpendicular to fibers) and trough (parallel to fibers) backscatter amplitude. The tissue segments were then treated with 10% NaOH to dissolve all of the cellular components, leaving only the intact ECM. Scanning electron micrographs (SEM) were obtained of tissue sections to reveal complete digestion of the cellular elements. The dimensions of the residual voids resulting from cell digestion were approximately the diameter of the intact myocytes (10-30 microm). These samples were reinsonified after seven days of treatment to compare the anisotropy of integrated backscatter. The magnitude of anisotropy of backscatter changed from 15.4 +/- 0.8 to 12.6 +/- 1.1dB for intact as compared with digested specimens. Because digestion of the myocardium leaves only extracellular sources of ultrasonic scattering, and because the isolated ECM exhibits similar ultrasonic anisotropy as does the intact myocardium, it is concluded that there is a direct association between the ECM and the anisotropy of backscatter within intact tissue. Thus, it is suggested that ultrasonic tissue characterization represents a potentially clinically applicable method for delineating the structure and function of the ECM.     

Anisotropy of the ultrasonic backscatter of myocardial tissue: II. Measurements in vivo

The purpose of this investigation was to determine the angular dependence of the backscatter from canine myocardial tissue in vivo and to compare it with the variation of backscatter over the cardiac cycle that has been recognized and reported previously. The backscatter was measured from regions of left ventricular wall in canine hearts in which the fibers of the muscle lay parallel to the surface of the heart and were oriented predominantly in a circumferential fashion. Because of technical considerations, the angle of insonification was varied systematically through two cycles in which the angle relative to the muscle fiber axes ranged from 60 degrees-120 degrees. Backscatter was maximum at angles of interrogation perpendicular to the myocardial fibers and minimum at those most acute (60 degrees) relative to the orientation of the fibers. The previously observed variation of integrated backscatter over the heart cycle was evident at each angle of interrogation. At end systole, the average maximum-to-minimum angular variation of integrated backscatter as 5.0 +/- 0.4 dB. At end diastole, the average maximum-to-minimum angular variation was 3.2 +/- 0.4 dB. Thus, even though angular dependence of the backscatter from tissues with directionally oriented structures is substantial, the anisotropy does not account for cardiac-cycle-dependent variation of backscatter. Accordingly, the angular dependence should be incorporated in approaches to quantitative tissue characterization with ultrasound.     

Anisotropy of the ultrasonic backscatter of myocardial tissue: I. Theory and measurements in vitro

This research addresses the variations in the ultrasonic backscatter from specimens consisting of a suspension of approximately aligned cylindrical scatterers in a fluid medium as a function of the angle of propagation in the sample. Predictions of the angular dependence of backscatter based on the time-domain Born approximation described by Rose and Richardson [J. H. Rose and J. M. Richardson, J. Nondestr. Eval. 3, 45-53 (1982)] were compared with experimental measurements of the backscatter from both tissue-mimicking phantoms consisting of graphite fibers suspended in gelatin and from canine myocardial tissue. The angular dependence of the backscatter was predicted and measured to be maximum for propagation perpendicular to the cylinder axes and minimum for propagation parallel to the axes. Maximum to minimum (i.e., perpendicular to parallel) changes in the integrated backscatter were predicted to be between 5 and 10 dB in the phantom. The corresponding quantity measured in both the phantom and in canine myocardial tissue was approximately 6 dB.     

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.     

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.     

Echolocation click sounds from wild inshore finless porpoise (Neophocaena phocaenoides sunameri) with comparisons to the sonar of riverine N. p. asiaeorientalis

Acoustic signals from wild Neophocaena phocaenoides sunameri were recorded in the waters off Liao-dong-wan Bay located in Bohai Sea, China. Signal analysis shows that N. p. sunameri produced "typical" phocoenid clicks. The peak frequencies f(p) of clicks ranged from 113 to 131 kHz with an average of 121+/-3.78 kHz (n=71). The 3 dB bandwidths delta f ranged from 10.9 to 25.0 kHz with an average of 17.5+/-3.30 kHz. The signal durations delta t ranged from 56 to 109 micros with an average 80+/-11.49 micros. The number of cycles N(c) ranged from 7 to 13 with an average of 9+/-1.48. With increasing peak frequency there was a faint tendency of decrease in bandwidth, which implies a nonconstant value of f(p)/delta f. On occasion there were some click trains with faint click energy presenting below 70 kHz, however, it was possibly introduced by interference effect from multiple pulses structures. The acoustic parameters of the clicks were compared between the investigated population and a riverine population of finless porpoise.     

Ultrasonic backscatter from flowing whole blood. II: Dependence on frequency and fibrinogen concentration

Earlier studies showed that ultrasonic backscatter from erythrocytes suspended in saline is a function of hematocrit and frequency and that it can be affected by flow disturbance. The experimental data agree well with the theories. Recently, studies have been extended to flowing whole blood. The results indicated that ultrasonic backscatter from flowing whole blood differs from that from saline suspensions of erythrocytes in that it is shear-rate dependent and species dependent. In the present article, data on the dependence of ultrasonic backscatter from flowing whole blood on frequency and on fibrinogen concentration are reported. It was found that ultrasonic backscatter from flowing whole blood also depends on fibrinogen concentration when red blood cell (RBC) aggregation exists. Moreover, when the blood is under conditions that favor RBC aggregation such as low shear rates, high fibrinogen concentration, or high hematocrits, Rayleigh scattering apparently is no longer sufficient to describe its scattering behavior.     

Spectral estimation for characterization of acoustic aberration

Spectral estimation based on acoustic backscatter from a motionless stochastic medium is described for characterization of aberration in ultrasonic imaging. The underlying assumptions for the estimation are: The correlation length of the medium is short compared to the length of the transmitted acoustic pulse, an isoplanatic region of sufficient size exists around the focal point, and the backscatter can be modeled as an ergodic stochastic process. The motivation for this work is ultrasonic imaging with aberration correction. Measurements were performed using a two-dimensional array system with 80 x 80 transducer elements and an element pitch of 0.6 mm. The f number for the measurements was 1.2 and the center frequency was 3.0 MHz with a 53% bandwidth. Relative phase of aberration was extracted from estimated cross spectra using a robust least-mean-square-error method based on an orthogonal expansion of the phase differences of neighboring wave forms as a function of frequency. Estimates of cross-spectrum phase from measurements of random scattering through a tissue-mimicking aberrator have confidence bands approximately +/- 5 degrees wide. Both phase and magnitude are in good agreement with a reference characterization obtained from a point scatterer.     

Quantum criticality in a Mott pn junction in an armchair carbon nanotube

In an armchair carbon nanotube pn junction the p and n regions are separated by a region of a Mott insulator, which can backscatter electrons only in pairs. We predict a quantum-critical behavior in such a pn junction. Depending on the junction's built-in electric field E, its conductance G scales either to zero or to 4e(2)/h as the temperature T is lowered. The two types of the G(T) dependence indicate the existence, at some special value of E, of an intermediate quantum-critical point with a finite conductance G<4e(2)/h. This makes the pn junction drastically different from a simple potential barrier in a Luttinger liquid.     

High frequency ultrasonic characterization of human vocal fold tissue

Recently, endolaryngeal sonography at frequencies ranging from 10 to 30 MHz has been found to be useful in diagnosing diseases of the vocal folds (VFs). However, image resolution can be further improved by ultrasound at higher frequencies, necessitating the measurement of high-frequency acoustic properties of VF tissue. The ultrasonic parameters of integrated backscatter, sound velocity, and frequency-dependent attenuation coefficient were measured in both the lamina propria (LP) and vocalis muscle (VM) of human VFs using a 47 MHz high-frequency ultrasonic transducer. The integrated backscatter was -173.44+/-6.14 (mean+/-s.d.) and -195.13+/-3.58 dB in the LP and VM, respectively, the sound velocity was 1667.68+/-44.9 and 1595.07+/-39.33 ms, and the attenuation coefficient at 47 MHz was 8.28+/-1.72 and 7.17+/-1.30 dBmm. The difference between these ultrasonic parameters may be attributed to variations in the structure and fiber concentrations in VF tissue. These results could serve as a useful clinical reference for the further development of high-frequency ultrasound devices for endolarynx sonography applications.     

Ultrasonic spectrum characterization of pig''''s pathological liver tissues

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骨小梁中超声背散射信号的频率分析及其微结构的估计

骨质疏松症是一种骨强度下降的全身性骨骼疾病,骨强度的下降是骨量减少和骨微结构退化的共同结果。相比于传统的超声透射方法,超声背散射法可提供更多的骨微结构信息,而对于松质骨结构的建模能有助于结构信息的获取。本文将骨小梁简化为单圆柱模型(圆柱状的单根骨小梁浸于骨髓中),并基于此模型对超声背散射与频率的关系进行分析。用铝线代替骨小梁做仿体实验,通过实验与理论结果的比较来验证单圆柱模型的可行性。     

Characterization of dense bovine cancellous bone tissue microstructure by ultrasonic backscattering using weak scattering models

A weak scattering model was proposed for the ultrasonic frequency-dependent backscatter in dense bovine cancellous bone, using two autocorrelation functions to describe the medium: one with discrete homogeneities (spherical distribution of equal spheres) and another, which considers tissue as an inhomogeneous continuum (densely populated medium). The inverse problem to estimate trabecular thickness of bone tissue has been addressed. A combination of the two autocorrelation functions was required to closely approximate the backscatter from bovine bone with various microarchitecture, given that the shape of trabeculae ranges from a rodlike to a platelike shape. Because of the large variation in trabecular thickness, both at an intraspecimen and an interspecimen level, thickness distributions for individual trabeculae for each bone specimen were obtained, and dominant trabecular sizes were determined. Comparison of backscatter measurements to theoretical predictions indicated that there were more than one dominant trabecular sizes that scatter sound for most specimens. Linear regression, performed between dominant trabecular thickness and estimated correlation length, showed significant linear correlation (R(2)=0.81). Attenuation due to scattering by a continuous distribution of scatterers was predicted to be linear over a frequency range from 0.3 to 0.9 MHz, suggesting a possibility that scattering may be a significant source of attenuation.     

Ultrasound attenuation estimation using backscattered echoes from multiple sources

The objective of this study was to devise an algorithm that can accurately estimate the attenuation along the propagation path (i.e., the total attenuation) from backscattered echoes. It was shown that the downshift in the center frequency of the backscattered ultrasound echoes compared to echoes obtained in a water bath was calculated to have the form Deltaf=mf(o)+b after normalizing with respect to the source bandwidth where m depends on the correlation length, b depends on the total attenuation, and f(o) is the center frequency of the source as measured from a reference echo. Therefore, the total attenuation can be determined independent of the scatterer correlation length by measuring the downshift in center frequency from multiple sources (i.e., different f(o)) and fitting a line to the measured shifts versus f(o). The intercept of the line gives the total attenuation along the propagation path. The calculations were verified using computer simulations of five spherically focused sources with 50% bandwidths and center frequencies of 6, 8, 10, 12, and 14 MHz. The simulated tissue had Gaussian scattering structures with effective radii of 25 mum placed at a density of 250 mm(3). The attenuation of the tissue was varied from 0.1 to 0.9 dB / cm-MHz. The error in the attenuation along the propagation path ranged from -3.5+/-14.7% for a tissue attenuation of 0.1 dB / cm-MHz to -7.0+/-3.1% for a tissue attenuation of 0.9 dB / cm-MHz demonstrating that the attenuation along the propagation path could be accurately determined using backscattered echoes from multiple sources using the derived algorithm.     

Ultrasonic absorption in polymer gel dosimeters

Ultrasonic absorption in polymer gel dosimeters was investigated. An ultrasonic interferometer was used to study the frequency (f) dependence of the absorption coefficient (alpha) in a polyacrylamide gel dosimeter (PAG) in the frequency range 5-20 MHz. The frequency dependence of ultrasonic absorption deviated from that of an ideal viscous fluid. The presence of relaxation mechanisms was evidenced by the frequency dependence of alpha/f(2) and the dispersion in ultrasonic velocity. It was concluded that absorption in polymer gel dosimeters is due to a number of relaxation processes which may include polymer-solvent interactions as well as relaxation due to motion of polymer side groups.The dependence of ultrasonic absorption on absorbed dose and formulation was also investigated in polymer gel dosimeters as a function of pH and chemical composition. Changes in dosimeter pH and chemical composition resulted in a variation in ultrasonic dose response curves. The observed dependence on pH was considered to be due to pH induced modifications in the radiation yield while changes in chemical composition resulted in differences in polymerisation kinetics.     

Improved scatterer size estimation using backscatter coefficient measurements with coded excitation and pulse compression

Scatterer size estimates from ultrasonic backscatter coefficient measurements have been used to differentiate diseased tissue from normal. A low echo signal-to-noise ratio (eSNR) leads to increased bias and variance in scatterer size estimates. One way to improve the eSNR is to use coded excitation (CE). The normalized backscatter coefficient was measured from three tissue-mimicking phantoms by using CE and conventional pulsing (CP) techniques. The three phantoms contained randomly spaced glass beads with median diameters of 30, 45, and 82 mum, respectively. Measurements were made with two weakly focused, single-element transducers (f(0)=5 MHz and f(0)=10 MHz). For CE, a linear frequency modulated chirp with a time bandwidth product of 40 was used and pulse compression was accomplished by the use of a Wiener filter. Preliminary results indicated that improved estimation bias versus penetration depth was obtained by using CE compared to CP. The depth of penetration, where the accuracy of scatterer diameter estimates (absolute divergence <25%) were obtained with the 10 MHz transducer, was increased up to 50% by using CE versus CP techniques. In addition, for a majority of the phantoms, the increase in eSNR from CE resulted in a modest reduction in estimate variance versus depth of penetration.     

Frequency-dependent ultrasonic differentiation of normal and diffusely diseased liver

The attenuation coefficient in 38 pathologically graded in vitro liver specimens was measured over a frequency range from 1.25-8 MHz and fitted to the power law model. The attenuation in the normal group (n = 17) exhibited a frequency dependence of the form 0.399f1.139; in the mild disease group (n = 13), it exhibited a dependence of the form 0.395f1.212; and in the moderate/severe disease group (n = 8), it exhibited a dependence of the form 0.391f1.325. Using a Student's t test, it is shown that, due to these differences in the frequency dependence, the statistical significance level at which the null hypothesis regarding the difference between the mean attenuation slopes of any two of these categories is rejected, is a strong function of frequency in the range of 1-4 MHz. The significance level relating to the difference between the normal and moderate/severe disease group is more than one order of magnitude better than the other categories. In all cases, no substantial improvement occurs beyond 4 MHz. It is also shown that attenuation slope values at 3 MHz confirm in vivo literature results obtained via different techniques.