Ultrasonic Backscatter Research Articles

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.

Normalization of catecholamine production following resection of phaeochromocytoma positively influences carotid vascular remodelling

To evaluate the influence of plasma catecholamines on the vascular structure in humans, the effects of catecholamine normalization on the carotid wall of patients with phaeochromocytoma (PHEO) were investigated. A prospective study in patients with PHEO before and after (first follow-up: 20.5+/-1.8 months, second follow-up: 31.5+/-2.2 months) successful surgery was conducted in the University Referral Center for Blood Pressure Diseases. Ten consecutive patients with PHEOs and ten age- and blood pressure-matched controls were investigated. Intima-media thickness (IMT) by two-dimensional conventional ultrasonography and corrected ultrasonic integrated backscatter signal (C-IBS) analysis of carotid arteries were investigated in basal conditions and after mass removal. In PHEOs, at variance with the expected reduction in metanephrines and catecholamines, no variation in body weight, blood pressure and lipid profile was observed after operation. IMT and C-IBS values in patients with PHEO were greater (at least P<0.01) than in controls. At long-term follow-up after surgery, a significant reduction in mean carotid IMT (P<0.0009) and C-IBS (P<0.009) values was observed. A significant correlation (r=0.54, P<0.03) was found between absolute reduction in C-IBS values and absolute decrement in urinary normetanephrine levels. Our study shows that normalization of catecholamine levels after the removal of PHEO improves carotid IMT and reduces carotid wall fibrosis even without influencing blood pressure and lipid profile. These findings confirm that high catecholamine tone in humans directly influences vascular remodelling of carotid arteries.

Improved cancer detection and classification using multi‐parameter quantitative ultrasound

Quantitative ultrasound (QUS) has been used successfully to differentiate benign from malignant solid tumors in animal models of breast cancer. In these studies, QUS made use of estimates of average scatterer diameter (ASD) and average acoustic concentration (AAC) from the ultrasonic backscatter. However, initial attempts to classify different kinds of malignant tumors based on ASD and AAC estimates were not successful. New models for ultrasonic backscatter were created by considering the cytoskeletal structure of cells. In addition, the homodyned K distribution was used to model the amplitude of the envelope from regions‐of‐interest in the malignant tumors. The homodyned K distribution yielded two parameters: the S parameter, which quantified the randomness of scatterer spacings, and the β parameter, which quantified the amount of clustering of scatterers in the interrogated tissue. Statistically significant differences (P < 0.05) were observed between average S and β parameters from the malignant tumors...

Diffuse ultrasonic backscatter from cortical bone

Diffuse ultrasonic backscatter techniques have been used primarily for characterization of microstructure in structural materials such as polycrystalline metals. Such measurements exploit the spatial variance of the signals from a modified pulse‐echo technique. In this presentation, experiments are discussed using this technique on samples of porcine cortical bone at center frequencies of 15, 20, and 25 MHz. The time domain results obtained are analyzed with respect to a single‐scattering model that includes statistical information about the microstructure. In addition, the model includes a rigorous description of the transducer beam pattern as it interacts with the liquid‐sample. These results provide information regarding the ability of single‐scattering models to capture the ultrasound propagation in such materials.

Diffuse ultrasonic backscatter at oblique incidence for heterogeneous solids

Diffuse ultrasonic backscatter techniques are useful for probing heterogeneous materials. They can be used to extract microstructural parameters and to detect flaws which cannot be detected by conventional ultrasonic techniques. Such experiments, usually done using a modified pulse-echo technique, utilize the spatial variance of the signals as a primary measure of microstructure. Quantitative ultrasonic scattering models include components of both transducer beams as well as microstructural scattering information. Of particular interest for interpretation of many experiments is the propagation through a liquid-solid interface at normal and oblique incidence. Here, the Wigner distribution of the beam pattern of an ultrasonic transducer through a liquid-solid interface is used in conjunction with the stochastic wave equation to model this scattering problem within a single scattering formulism. The Wigner distribution represents a distribution in space and time of the spectral energy density as a function of wave vector and frequency. A Gaussian beam is used to model the transducer beam pattern. The scattered response in the time domain is then compared with experimental results for materials of common interest. These results are anticipated to impact ultrasonic nondestructive evaluation and characterization of heterogeneous media.

Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. With in vitro experiments, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317dB∕cm∕MHz, signal-to-noise ratios&amp;gt;28dB and kR&amp;lt;2.7 (k being the wave number and R the aggregate radius).

Influence of microarchitecture alterations on ultrasonic backscattering in an experimental simulation of bovine cancellous bone aging

An experimental model which can simulate physical changes that occur during aging was developed in order to evaluate the effects of change of mineral content and microstructure on ultrasonic properties of bovine cancellous bone. Timed immersion in hydrochloric acid was used to selectively alter the mineral content. Scanning electron microscopy and histological staining of the acid-treated trabeculae demonstrated a heterogeneous structure consisting of a mineralized core and a demineralized layer. The presence of organic matrix contributed very little to normalized broadband ultrasound attenuation (nBUA) and speed of sound. All three ultrasonic parameters, speed of sound, nBUA and backscatter coefficient, were sensitive to changes in apparent density of bovine cancellous bone. A two-component model utilizing a combination of two autocorrelation functions (a densely populated model and a spherical distribution) was used to approximate the backscatter coefficient. The predicted attenuation due to scattering constituted a significant part of the measured total attenuation (due to both scattering and absorption mechanisms) for bovine cancellous bone. Linear regression, performed between trabecular thickness values and estimated from the model correlation lengths, showed significant linear correlation, with R(2)=0.81 before and R(2)=0.80 after demineralization. The accuracy of estimation was found to increase with trabecular thickness.

Extended three-dimensional impedance map methods for identifying ultrasonic scattering sites.

The frequency-dependent ultrasound backscatter from tissues contains information about the microstructure that can be quantified. In many cases, the anatomic microstructure details responsible for ultrasonic scattering remain unidentified. However, their identification would lead to potentially improved methodologies for characterizing tissue and diagnosing disease from ultrasonic backscatter measurements. Recently, three-dimensional (3D) acoustic models of tissue microstructure, termed 3D impedance maps (3DZMs), were introduced to help to identify scattering sources [J. Mamou, M. L. Oelze, W. D. O'Brien, Jr., and J. F. Zachary, "Identifying ultrasonic scattering sites from 3D impedance maps," J. Acoust. Soc. Am. 117, 413-423 (2005)]. In the current study, new 3DZM methodologies are used to model and identify scattering structures. New processing procedures (e.g., registration, interpolations) are presented that allow more accurate 3DZMs to be constructed from histology. New strategies are proposed to construct scattering models [i.e., form factor (FF)] from 3DZMs. These new methods are tested on simulated 3DZMs, and then used to evaluate 3DZMs from three different rodent tumor models. Simulation results demonstrate the ability of the extended strategies to accurately predict FFs and estimate scatterer properties. Using the 3DZM methods, distinct FFs and scatterer properties were obtained for each tumor examined.

Very Early Stage Detection of Acute Myocardial Infarction by Harmonic Ultrasonic Integrated Backscatter

To study the very early diagnosis of acute myocardial infarction (AMI) by harmonic imaging ultrasonic integrated backscatter (IBS). Thirty normal persons, 68 cases with AMI, of whom 28 cases were at the very early stage of acute myocardial infarction (in 2 h), and 40 cases with acute myocardial infarction (in 2 to 12 h) were examined by IBS and the cyclic variation of integrated backscatter (CVIB) with HP-5500 ultrasonic system in different segment (the segment of myocardial infarction and no myocardial infarction). In the segment of AMI of the very early stage (in 2 h) the IBS (dB) is much higher than that of the segment of no AMI (18.7 versus 8.3), p < 0.001, the CVIB (dB) are lower (6.1 versus 7.6), p < 0.001. But at that time there are no obvious changes in ECG. In the other 40 cases with AMI in 2 to 12 h, IBS in the segment of AMI is obviously higher than the normal person and no infarction segment in the same heart (21.3:8.3, 20.2:8.5) p < 0.05, but CVIB (dB) is obviously lower than the normal person and no infarction segment in the same heart (5.8:7.6, 5.9:9.4) p < 0.05 the changes of the ultrasonic is coincidence with ECG. IBS (dB) are very obvious just as in ECG. The result demonstrates that ultrasonic tissue characterization with harmonic imaging integrated backscatter can be used for diagnosis in the very early stage of AMI, and can judge the segment range of AMI and function of the whole heart. (E-mail: wuxiaoqing48@hotmail.com)

Detection and monitoring of cardiotoxicity—what does modern cardiology offer?

With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.

Measurement of Ultrasonic Backscattering Property for Assessment of RBC Aggregation

Measurement of Ultrasonic Backscattering Property for Assessment of RBC Aggregation

Sensitive ultrasonic delineation of steroid treatment in living dystrophic mice with energy-based and entropy-based radio frequency signal processing.

Duchenne muscular dystrophy is a severe wasting disease, involving replacement of necrotic muscle tissue by fibrous material and fatty infiltrates. One primary animal model of this human disease is the X chromosome-linked mdx strain of mice. The goals of the present work were to validate and quantify the capability of both energy and entropy metrics of radio-frequency ultrasonic backscatter to differentiate among normal, dystrophic, and steroid-treated skeletal muscle in the mdx model. Thirteen 12-month-old mice were blocked into three groups: 4 treated mdx-dystrophic that received daily subcutaneous steroid (prednisolone) treatment for 14 days, 4 positive-control mdx-dystrophic that received saline injections for 14 days, and 5 negative-control animals. Biceps muscle of each animal was imaged in vivo using a 40-MHz center frequency transducer in conjunction with a Vevo-660 ultrasound system. Radio-frequency data were acquired (1 GHz, 8 bits) corresponding to a sequence of transverse images, advancing the transducer from "shoulder" to "elbow" in 100-micron steps. Data were processed to generate both "integrated backscatter" (log energy), and "entropy" (information theoretic receiver, H(f)) representations. Analyses of the integrated-backscatter values delineated both treated-and untreated-mdx biceps from normal controls (p < 0.01). Complementary analyses of the entropy images differentiated the steroid-treated and positive-control mdx groups (p < 0.01). To our knowledge, this study represents the first reported use of quantitative ultrasonic characterization of skeletal muscle in mdx mice. Successful differentiation among dystrophic, steroid-treated, and normal tissues suggests the potential for local noninvasive monitoring of disease severity and therapeutic effects.

Wigner distribution of a transducer beam pattern within a multiple scattering formalism for heterogeneous solids

Diffuse ultrasonic backscatter measurements have been especially useful for extracting microstructural information and for detecting flaws in materials. Accurate interpretation of experimental data requires robust scattering models. Quantitative ultrasonic scattering models include components of transducer beam patterns as well as microstructural scattering information. Here, the Wigner distribution is used in conjunction with the stochastic wave equation to model this scattering problem. The Wigner distribution represents a distribution in space and time of spectral energy density as a function of wave vector and frequency. The scattered response is derived within the context of the Wigner distribution of the beam pattern of a Gaussian transducer. The source and receiver distributions are included in the analysis in a rigorous fashion. The resulting scattered response is then simplified in the single-scattering limit typical of many diffuse backscatter experiments. Such experiments, usually done using a modified pulse-echo technique, utilize the variance of the signals in space as the primary measure of microstructure. The derivation presented forms a rigorous foundation for the multiple scattering process associated with ultrasonic experiments in heterogeneous media. These results are anticipated to be relevant to ultrasonic nondestructive evaluation of polycrystalline and other heterogeneous solids.

Mapping elasticity in human lenses using bubble-based acoustic radiation force

This study uses acoustic radiation pressure to displace a femtosecond laser-produced bubble in human lens tissue. Bubble displacement is monitored with low-amplitude, high-resolution ultrasound. Displacements are compensated by bubble size determined from ultrasonic backscatter. The Young's modulus is proportional to the inverse of the compensated displacement with the constant of proportionality determined from similar measurements in a controlled gelatin sample. Multiple measurements were obtained on 12 human lens specimens grouped into two age categories, middle-age (about 40 years old) and old-age (63–70 years old). There were 3 lenses from 2 donors in the middle-age group and 9 lenses from 5 donors in the old-age group. At each radial position, the median value was computed for all measurements within each group. For middle-age lenses, Young's modulus ranged from 5.2 kPa in the center to 1.1 kPa on the periphery. For old-age lenses, Young's modulus ranged from 10.6 kPa in the center to 1.4 kPa on the periphery. These values are the same order of magnitude as previous measurements using other techniques. The age related change in elasticity distribution is also similar to a previous study. Radially varying elasticity may provide insight into the mechanics of accommodation.

Regional Variation in the Measured Apparent Ultrasonic Backscatter of Mid-Gestational Fetal Pig Hearts

The goal of this study was to characterize and compare regional backscatter properties of fetal hearts through measurements of the apparent integrated backscatter. Sixteen excised, formalin-fixed fetal pig hearts, representing an estimated 53 to 63 days of gestation, were investigated. Spatially localized measurements of integrated backscatter from these specimens were acquired using a 50 MHz single-element transducer. The apparent integrated backscatter measurements demonstrate different patterns of backscatter from the myocardium of the right ventricle compared with that of the left ventricle. These backscatter measurements appear to be consistent with the anisotropy of the fiber orientation observed in histologic assessment of the same specimens. For each of the 16 hearts, the apparent integrated backscatter from the right ventricular myocardium was larger than that from the left ventricular myocardium, exhibiting mean apparent backscatter values of –35.9 ± 2.0 dB and –40.1 ± 1.9 dB (mean ± standard deviation; n = 16; p < 0.001), respectively. This study suggests that the intrinsic ultrasonic properties of the left and right ventricular myocardium are distinct in fetal pig hearts at mid-gestation. (E-mail: mrh@wuphys.wustl.edu)

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.

Experimental ultrasound characterization of red blood cell aggregation using the structure factor size estimator

The frequency dependence of the ultrasonic backscattering coefficient (BSC) was studied to assess the level of red blood cell (RBC) aggregation. Three monoelement focused wideband transducers were used to insonify porcine blood sheared in a Couette flow from 9 to 30 MHz. A high shear rate was first applied to promote disaggregation. Different residual shear rates were then used to promote formation of RBC aggregates. The structure factor size estimator (SFSE), a second-order data reduction model based on the structure factor, was applied to the frequency-dependent BSC. Two parameters were extracted from the model to describe the level of aggregation at 6% and 40% hematocrits: W, the packing factor, and D the aggregate diameter, expressed in number of RBCs. Both parameters closely matched theoretical values for nonaggregated RBCs. W and D increased during aggregation with stabilized values modulated by the applied residual shear rate. Furthermore, parameter D during the kinetics of aggregation at 6% hematocrit under static conditions correlated with an optical RBC aggregate size estimation from microscopic images (r(2)=0.76). To conclude, the SFSE presents an interesting framework for tissue characterization of partially correlated dense tissues such as aggregated RBCs.

Gaseous Microemboli Sizing in Extracorporeal Circuits Using Ultrasound Backscatter

This paper describes efforts to estimate the size of gaseous microemboli (GME) in extracorporeal blood circuits based on the amplitude of backscattered ultrasound, starting with analytic modeling of the scattering behavior of GME in blood. After neglecting resonance effects, this model predicts a linear relationship between the amplitude of backscattered echoes and the diameter of GME. Computer simulations based on the cylindrical acoustic finite integration technique were performed to test some of the simplifying assumptions of the analytical model, with the simulations predicting small deviations from the linear approximation that could be treated as random scatter. Ultrasonic and microscopic measurements of injected GME were then performed on a test circuit to determine the linear correlation coefficient between echo amplitude and GME diameter in conditions like those employed in real cardiopulmonary bypass (CPB) circuits. The correlation coefficient determined through this study was further validated in a closed-loop CPB circuit using canine blood. This study shows that the amplitude of ultrasonic backscattered echoes can be used to accurately estimate the size distribution of a population of detected GME when the spacing of emboli is great enough to minimize interference and other multi-path scattering effects. With the high flow rates found in CPB circuits, typically ranging from 2 to 6 L per minute (equivalent to a flow velocity of 0.3 to 1 m/s through the circuit tubing), this assumption will be valid even when hundreds of emboli per second pass through the circuit. Therefore, sizing of GME using the ultrasonic backscatter models described in this paper is a viable method for estimating embolic load delivered to a patient during a CPB procedure. (E-mail: lyncht@lunainnovations.com)

High-frequency ultrasound backscattering by blood: Analytical and semianalytical models of the erythrocyte cross section

This paper proposes analytical and semianalytical models of the ultrasonic backscattering cross section (BCS) of various geometrical shapes mimicking a red blood cell (RBC) for frequencies varying from 0 to 90 MHz. By assuming the first-order Born approximation and by modeling the shape of a RBC by a realistic biconcave volume, different scattering behaviors were identified for increasing frequencies. For frequencies below 18 MHz, a RBC can be considered a Rayleigh scatterer. For frequencies less than 39 MHz, the general concept of acoustic inertia tensor is introduced to describe the variation of the BCS with the frequency and the incidence direction. For frequencies below 90 MHz, ultrasound backscattering by a RBC is equivalent to backscattering by a cylinder of height 2 microm and diameter 7.8 microm. These results lay the basis of ultrasonic characterization of RBC aggregation by proposing a method that distinguishes the contribution of the individual RBC acoustical characteristics from collective effects, on the global blood backscattering coefficient. A new method of data reduction that models the frequency dependence of the ultrasonic BCS of micron-sized weak scatterers is also proposed. Applications of this method are in tissue characterization as well as in hematology.

Correlation between N‐Terminal Pro B‐Natriuretic Peptide and Ultrasonic Backscatter: Implications for Diastolic Dysfunction in Hypertension

This study was designed to determine how N-terminal pro brain-natriuretic peptide (NT-proBNP) levels correlate with cyclic variation of integrated backscatter (CVIBS) as a reflection of abnormal diastolic function in hypertension. Forty essentially hypertensive patients were studied. CVIBS values were obtained from the septal wall in the parasternal long-axis view. Twelve had normal diastolic function, 18 had impaired relaxation, and 10 had pseudonormal pattern. Patients with normal diastolic function had a mean NT-proBNP concentration of 34 +/- 17 pg/ml and a mean CVIBS value of 7.1 +/- 0.9 dB; those with impaired relaxation had a mean NT-proBNP concentration of 71 +/- 25 pg/ml and a mean CVIBS value of 6.7 +/- 1.1 dB. Patients with pseudonormal pattern had the highest NT proBNP levels (206 +/- 75 pg/ml) and lowest CVIBS values (5.7 +/- 0.9 dB). An NT-proBNP value of 62 pg/ml had a sensitivity of 83% and a specificity of 91%; a CVIBS value of 7.2 dB had a sensitivity of 83.3% and a specificity of 66.7% for detecting diastolic dysfunction. An NT-proBNP value of 120 pg/ml had a sensitivity of 76% and a specificity of 96%; a CVIBS value of 6.1 dB had a sensitivity of 87.5% and a specificity of 75% for detecting severe diastolic dysfunction. A close correlation was found between the NT-proBNP and CVIBS values (r: 0.54, P < 0.05). Combinative use of NT-proBNP and CVIBS can detect the presence of diastolic abnormalities on echocardiography. A good correlation was found between the NT-proBNP and CVIBS values in detecting diastolic dysfunction in essentially hypertensive patients.