Contrast-enhanced subharmonic aided pressure estimation for assessment of intracranial pressure in vivo.

BACKGROUND: Intracranial pressure (ICP) monitoring in children currently requires invasive techniques. Subharmonic aided pressure estimation (SHAPE) uses contrast-enhanced ultrasound (CEUS) to measure intravascular and interstitial pressure, but utility in ICP measurements has yet to be explored. OBJECTIVE: The objective of this study was to investigate SHAPE as a novel tool for noninvasive ICP measurements in fetal lambs. MATERIALS AND METHODS: Eighteen fetal lambs at 107-139 days gestational age (term = 145 days) underwent subdural ICP catheter placement. The brain was imaged in the coronal plane in CEUS mode optimized for SHAPE, while infusing an US contrast agent into the fetal circulation. After SHAPE calibration, saline was infused via the subdural catheter to increase ICP. Five-second SHAPE cine clips were obtained at various ICPs. Subharmonic intensity values of the whole brain and thalami were correlated with ICP values using mixed effects linear regression analyses and the strength of the relationship was evaluated by Spearman's rank-order correlation. RESULTS: Forty-nine experiments produced 723 datapoints, including SHAPE intensity values and mean ICP measurements. There was a statistically significant inverse relationship between SHAPE intensity values and ICP measurements in the whole brain and thalami (median rho value - 0.58 and - 0.56, respectively). CONCLUSION: SHAPE intensity values of the brain demonstrate an inverse and statistically significant correlation with in vivo ICP measurements in an animal model.

A Preliminary Study of Quantitative Ultrasound for Cancer-Risk Assessment of Thyroid Nodules.

Background: Gray-scale, B-mode ultrasound (US) imaging is part of the standard clinical procedure for evaluating thyroid nodules (TNs). It is limited by its instrument- and operator-dependence and inter-observer variability. In addition, the accepted high-risk B-mode US TN features are more specific for detecting classic papillary thyroid cancer rather than the follicular variant of papillary thyroid cancer or follicular thyroid cancer. Quantitative ultrasound (QUS) is a technique that can non-invasively assess properties of tissue microarchitecture by exploiting information contained in raw ultrasonic radiofrequency (RF) echo signals that is discarded in conventional B-mode imaging. QUS provides quantitative parameter-value estimates that are a function of the properties of US scatterers and microarchitecture of the tissue. The purpose of this preliminary study was to assess the performance of QUS parameters in evaluating benign and malignant thyroid nodules. Methods: Patients from the Thyroid Health Center at the Boston Medical Center were recruited to participate. B-mode and RF data were acquired and analyzed in 225 TNs (24 malignant and 201 benign) from 208 patients. These data were acquired either before (167 nodules) or after (58 nodules) subjects underwent fine-needle biopsy (FNB). The performance of a combination of QUS parameters (CQP) was assessed and compared with the performance of B-mode risk-stratification systems. Results: CQP produced an ROC AUC value of 0.857 ± 0.033 compared to a value of 0.887 ± 0.033 (p=0.327) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.880 ± 0.041 (p=0.367) for the American Thyroid Association (ATA) risk-stratification system. Furthermore, using a CQP threshold of 0.263 would further reduce the number of unnecessary FNBs in 44% of TNs without missing any malignant TNs. When CQP used in combination with ACR TI-RADS, a potential additional reduction of 49 to 66% in unnecessary FNBs was demonstrated. Conclusion: This preliminary study suggests that QUS may provide a method to classify TNs when used by itself or when combined with a conventional gray-scale US risk-stratification system and can potentially reduce the need to biopsy TNs.

Fluidic measurement of electric field sensitivity of Ti-GaAs Schottky junction gated field effect biosensors.

We report the electric field and pH sensitivity of fluid gated metal-semiconductor hybrid (MSH) Schottky structures consisting of a Titanium layer on n-type GaAs. Compared to standard field-effect sensors, the MSH Schottky structures are 21 times more sensitive to electric field of -46.6 V/cm and show about six times larger resistance change as pH of the solution is decreased from 8.17 to 5.54. The potential change at the fluidic gate and passivation layer interface by bias voltages and pH are mirrored by the metal shunt, resulting in larger depletion widths under the Schottky junction and resistance change as compared to sensors with no Schottky junction. 2D numerical simulation results are in good agreement with the measured data and suggest thinner mesa with lower doping density can further increase device sensitivity.

Finite amplitude measurements of the nonlinear parameter B/A for liquid mixtures spanning a range relevant to tissue harmonic mode.

The objective of this investigation was to measure the nonlinear parameter B/A using an enhanced finite amplitude distortion technique, based on nonlinear propagation effects analogous to those associated with tissue harmonic imaging. These measurements validate an improved method for measuring the nonlinear parameter B/A, the small-signal speed of sound, and the attenuation coefficient from a single set of ultrasonic measurements. To test the method, measurements were performed on 11 different mixtures of isopropyl alcohol (isopropanol) and water that span the range of concentrations from 0% to 100% isopropanol. Results for B/A ranging from approximately five to 11 were found to be reproducible and in good agreement with previously published values obtained using a thermodynamic method.

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.

Sensitive ultrasonic detection of dystrophic skeletal muscle in patients with duchenne muscular dystrophy using an entropy-based signal receiver.

The dystrophinopathies comprise a group of X-linked genetic diseases that feature dystrophin deficiency. Duchenne and Becker muscular dystrophy are characterized by progressive weakness and wasting of skeletal, smooth, and/or cardiac muscle. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, with an incidence of 1:3500 male births. Despite understanding the structural and genetic basis for DMD, the pathogenesis and clinical basis for more severe involvement in specific skeletal muscle groups and the heart are poorly understood. Current techniques, such as strength testing for monitoring progress of disease and therapy in DMD patients, are imprecise and physically demanding for test subjects. Ultrasound is well-suited to detect changes in structure and organization in muscle tissue in a manner that makes low demands on the patient. Therefore, we investigated the use of ultrasound to quantitatively phenotype the remodeling process in patients with DMD. Beam-formed radio-frequency (RF) data were acquired from the skeletal muscles of nine DMD and five normal subjects imaged with a clinical imaging system (HDI5000 w/7 MHz probe applied above left biceps muscle). From these data, images were reconstructed using B-mode (log of analytic signal magnitude) and information-theoretic receivers (H(f)-receiver). H(f) images obtained from dystrophic muscle contained extensive "mottled" regions (i.e., areas with heterogeneous image contrast) that were not readily apparent from the B-Mode images. The 2-D autocorrelation of DMD H(f) images have broader peaks than those of normal subjects, which is indicative of larger scatterer sizes, consistent with pathologic changes of fibers, edema and fatty infiltration. Comparison of the relative peak widths (full width measured at 60% maximum) of the autocorrelation of the DMD and normal H(f) images shows a quantitative difference between the two groups (p < 0.005, student two-tailed paired t-test). Consequently, these imaging techniques may prove useful for longitudinal monitoring of disease progression and therapy.

Plane wave source with minimal harmonic distortion for investigating nonlinear acoustic properties.

The objective of this investigation is to introduce and validate a practical ultrasound source to be used in the investigation of the nonlinear material properties of liquids and soft tissues studied in vitro. Methods based on the progressive distortion of finite amplitude ultrasonic waves in the low megahertz frequency range are most easily implemented under the assumption of plane wave propagation. However, achieving an approximately planar ultrasonic field over substantial propagation distances can be challenging. Furthermore, undesired harmonic distortion of the ultrasonic field prior to insonification of the specified region of interest represents another serious limitation. This paper introduces an approach based on the use of the ultrasonic field emanating from a stainless-steel delay line. Both simulation and direct experimental measurement demonstrate that such a field exhibits relatively planar wave fronts to a good approximation (such that a 3-mm-diam receiver would be exposed to no more than 3 dB of loss across its face) and is free from the significant harmonic distortion that would occur in a conventional water path.

Ultrasonic detection of the anisotropy of protein cross linking in myocardium at diagnostic frequencies.

Increased myocardial stiffness in aging and diabetes that may result in pathologies such as diastolic dysfunction has been attributed, in part, to an increase in cross linking of extracellular matrix proteins such as collagen. With the development of new approaches to cardiovascular therapy, it becomes increasingly important to develop noninvasive approaches for monitoring changes in myocardial cross linking. The objective of this study was to use ultrasound at frequencies used in clinical echocardiography to measure changes in myocardial attenuation resulting from increased cross linking as a function of angle of insonification over a complete rotation. Through-transmission radiofrequency-based measurements were performed on 36 specimens from 12 freshly excised ovine hearts at room temperature, which were then fixed in formalin to induce protein cross linking prior to repeated measurements. For angles near perpendicular to the myofiber direction, the measured slope of attenuation increased from 0.52 +/- 0.07 dB/(cm MHz) (mean +/- one standard deviation) for freshly excised to 0.85 +/- 0.08 dB/(cm MHz) for formalin-fixed myocardium. In contrast, results for parallel insonification exhibit considerable overlap (1.88 +/- 0.17 for freshly excised and 1.75 +/- 0.19 dB/(cm MHz) for formalin-fixed myocardium). Results of this study suggest that the response of the extracellular collagenous matrix to changes in cross linking is directionally dependent. The anisotropy of ultrasonic attenuation thus may provide an approach for noninvasive monitoring of the extent and progression of myocardial disease associated with changes in protein cross linking. Accounting for effects due to anisotropy may be essential for the future detection of such changes using ultrasonic attenuation in vivo.

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.

The frequency dependence of ultrasonic velocity and the anisotropy of dispersion in both freshly excised and formalin-fixed myocardium.

The objectives of this study were to measure the frequency dependence of the ultrasonic velocity in myocardium and to quantify the frequency dependence of phase velocity as a function of the insonification angle relative to the predominant direction of the myofibers. Broadband phase spectroscopy data were acquired, spanning a frequency range of 3 to 8 MHz. Measurements were made on 36 tissue specimens cored from 12 freshly excised lamb hearts and were repeated after fixation with formalin. Measured phase velocities were found to be well characterized by a logarithmic fit. For freshly excised myocardium, the dispersion over the 3 to 8 MHz bandwidth was dependent on the direction of insonification, ranging from 1.2 m/s change for perpendicular insonification (across the myofibers) to 3.7 m/s for parallel insonification (along the myofibers). The effects of formalin-fixation resulted in a significant increase in dispersion for perpendicular insonification, but did not appreciably alter the dispersion for parallel insonification.

Impact of propagation through an aberrating medium on the linear effective apodization of a nonlinearly generated second harmonic field.

Techniques based on the nonlinearly generated second harmonic signal (tissue harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as the standard in two-dimensional echocardiography. Enhancements to the compactness of the nonlinearly generated second harmonic (2f) field component with respect to the fundamental (1f) field component are widely considered to be among the factors contributing to the observed image quality improvements. The objective of this study was to measure the impact of phase and amplitude aberrations resulting from propagation through an inhomogeneous tissue, on the beamwidths associated with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and the linearly propagated, effective apodization signal at the same (21) frequency. Modifications to the transmit characteristics of a phased-array imaging system were validated with hydrophone measurements. Results demonstrate that the characteristics of the diffraction pattern associated with the linear-propagation effective apodization transmit case were found to be in good agreement with the detailed spatial characteristics of the nonlinearly generated second harmonic field. The effects of the abdominal wall tissue aberrators are apparent for all three of the beam profiles studied. Consistent with the improved image quality associated with harmonic imaging, the aberrated nonlinearly generated second harmonic beam was shown to remain more compact than the corresponding aberrated fundamental beam patterns in the presence of the interposed aberrator.

Toward 3-D Echocardiographic Determination of Regional Myofiber Structure.

As a step toward the goal of relating changes in underlying myocardial structure to observed altered cardiac function in the hearts of individual patients, this study addresses the feasibility of creating echocardiography-derived maps of regional myocardial fiber structure for entire, intact, excised sheep hearts. Backscatter data were obtained from apical echocardiographic images acquired with a clinical ultrasonic imaging system and used to determine local fiber orientations in each of seven hearts. Systematic acquisition across the entire heart volume provided information sufficient to give a complete map for each heart. Results from the echocardiography-derived fiber maps compare favorably with corresponding results derived from diffusion tensor magnetic resonance imaging. The results of this study provide evidence of the feasibility of using echocardiographic methods to generate individualized whole heart fiber maps for patients.

Anisotropy of apparent backscatter in the short-axis view of mouse hearts.

The goals of this investigation were to measure the anisotropy of backscattered ultrasound observed in the short-axis view of mouse hearts in systole and diastole and to compare these measurements with predictions from a computer simulation. Measurements of midmyocardial apparent backscatter were obtained from analyses of the hearts of seven wild-type mice using a clinical imaging system utilizing a linear array with a nominal center frequency of 13 MHz. A computer model simulating the short-axis view was implemented based on previous measurements of the angle of insonification dependence of myocardial backscatter and attenuation. Results demonstrate that the measured backscatter was largest for those myocardial regions corresponding to approximately perpendicular insonification relative to the myofibers and the smallest for regions of approximately parallel insonification, with the minimum to maximum values of apparent backscatter differing by approximately 10 dB. The measured anisotropy of backscatter was similar for end-systole and end-diastole and was in good agreement with the predicted anisotropy obtained from the computer simulations.

Estimating myocardial attenuation from M-mode ultrasonic backscatter.

The objective of this investigation was to determine whether measurements of myocardial attenuation can be obtained from analyses of M-mode images. We exploited the inherent anisotropy of myocardial properties as a means of systematically varying the attenuation to evaluate this M-mode image-based method for myocardial tissue characterization. A commercially available ultrasonic imaging system was used to acquire M-mode images of 24 excised cylindrical specimens from six formalin-fixed sheep hearts that were analyzed using video signal analysis. Data were compensated for the presence of bright intramural myocardial echoes, a potentially significant contributor to uncertainty in measurements of attenuation from backscattered ultrasound. The estimated attenuation coefficient in dB/cm at an effective center frequency of 2.75 MHz as a function of angle of insonification for measurements obtained from analyses of M-mode images is presented. Given a linear frequency-dependence of attenuation in myocardial tissue over frequencies ranging from 1.5 MHz to 8 MHz, as has been previously reported, M-mode image-based analyses were used to estimate the slope of attenuation. Results showed slopes of attenuation (over a -10 dB transmit bandwidth of 1.875 MHz to 3.75 MHz) ranging from 1.00 +/- 0.07 to 1.81 +/- 0.08 dB/(cm.MHz) for perpendicular and parallel insonification, respectively. These values were in good agreement with contemporaneously measured values (0.99 +/- 0.02 to 1.77 +/- 0.04 dB/(cm.MHz)) obtained over a frequency bandwidth of 4 MHz to 7 MHz using a through-transmission radio-frequency-based approach. These data suggest that robust measurements of myocardial attenuation can be obtained from analyses of M-mode images and that this method may be diagnostically feasible in the clinical setting.

4-D spatiotemporal analysis of ultrasound contrast agent dispersion for prostate cancer localization: a feasibility study.

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results.

Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids.

BACKGROUND: Low levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials. OBJECTIVE: We examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo. METHODS: Our novel site-specific gene delivery system was examined in naïve rat model and comprised the following steps: (1) intravenous co-administration of a solution containing acoustically active microspheres (Optison™, GE Healthcare, Princeton, New Jersey) and human ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres within the liver vasculature; (3) External application of locally-directed acoustic energy, (4) induction of microsphere disruption and in situ sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression of human ApoA-I protein; and (6) elevation of serum HDL-C. RESULTS: Co-administration of ApoA-I plasmids and acoustic microspheres, activated by external ultrasound energy, resulted in transcription and production of human ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05). CONCLUSIONS: HDL-C was increased in rats following ultrasound directed delivery of human ApoA-I plasmids by microsphere sonoporation. The present method provides a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation, potentially permitting the use of a minimally-invasive ultrasound-based, gene delivery system for treating individuals with low HDL-C.

Potential relationships among myocardial stiffness, the measured level of myocardial backscatter ("image brightness"), and the magnitude of the systematic variation of backscatter (cyclic variation) over the heart cycle.

BACKGROUND: In a number of recently published studies comparing measurements from patients with those from control subjects, a decreased magnitude of the systematic variation of backscattered energy over the heart cycle (cyclic variation) is accompanied by an increased level of overall myocardial backscatter (calibrated myocardial image brightness) when measured at a specific phase of the heart cycle (eg, end systole or end diastole). The goal of this study was to investigate whether this observation is consistent with predictions based on a model of the mechanisms of cyclic variation incorporating changes in relative intracellular and extracellular acoustic impedance over the heart cycle. METHODS: A previously described 3-component Maxwell-type model of muscle mechanics representing cardiac cell mechanical behavior was utilized to predict the systematic variation in the relative acoustic impedance differences between intracellular and extracellular elastic properties over the heart cycle and hence the observed magnitude of cyclic variation and overall myocardial scattering level. Predictions were obtained for a series of specific values of relative intracellular and extracellular acoustic impedance. RESULTS: Results indicate that the predicted magnitude of cyclic variation can be directly related to the overall myocardial backscatter level. For example, specific changes in the acoustic impedance (stiffness properties) of the extracellular matrix without any change in the intracellular acoustic impedance result in predicted values of -43.5 dB, -38.5 dB, and -33.5 dB for end-diastolic myocardial backscatter levels with corresponding values of 5.0 dB, 2.5 dB, and 1.3 dB for the predicted magnitude of cyclic variation, respectively. CONCLUSION: This study suggests that observed decreases in the magnitude of cyclic variation with concomitant increases in the measured overall myocardial backscatter level are consistent with predictions from a model based on the relative acoustic impedance differences between intracellular and extracellular elastic properties over the heart cycle. These results suggest that ultrasonic backscatter measurements may provide a noninvasive approach for assessing some relationships among myocardial stiffness, degree of fibrosis, and contractile performance.

Ultrasonic tissue characterization of the mouse myocardium: successful in vivo cyclic variation measurements.

BACKGROUND: Measurements of the systematic variation of backscattered ultrasonic energy from myocardium during the heart cycle (cyclic variation) have been successfully used to characterize a wide spectrum of cardiac pathologies in large animal models and human subjects. The purpose of this study was to evaluate the feasibility of extending cyclic variation measurements to the study of genetically manipulated mouse models of cardiac diseases as a method for developing further insights into the disease-altered properties of the myocardium and its characterization with ultrasound. METHODS: Parasternal long-axis images of the heart were obtained in 9 wild-type mice under light anesthesia using a commercial imaging system with a 15-MHz nominal center frequency linear array. Images of a tissue-mimicking phantom and the mouse hearts were obtained for a series of specific receiver gains for each of a series of specific dynamic range settings. Analyses of these data formed the basis for gray-scale image calibration. Cyclic variation measurements were obtained by determining the average gray-scale value for a region of interest placed in the midmyocardium of the posterior wall for each frame acquired during 4 cardiac cycles and converting these mean gray-scale values to backscatter values expressed in decibels using the determined calibration. Results are expressed in terms of the magnitude and time delay of cyclic variation. To evaluate repeatability of these measurements the same group of mice underwent the identical imaging protocol 2 weeks after the first study. RESULTS: The mean magnitude of cyclic variation was found to be 4.6 +/- 0.2 dB with a corresponding normalized time delay of 1.02 +/- 0.03 for data averaged over all dynamic range settings. There was no significant difference among results obtained with each of the dynamic range settings. A comparison of these results with those from data acquired 2 weeks after the initial study showed no significant difference. CONCLUSION: This study represents the first reported measurement of cyclic variation in mice and demonstrates that reliable cyclic variation measurements can be obtained among individual animals and over different time points and, hence, forms the basis for subsequent investigations addressing specific cardiac pathologies and effects arising from myocardial anisotropy.

Spatial coherence of backscatter for the nonlinearly produced second harmonic for specific transmit apodizations.

To be successful, correlation-based, phase-aberration correction requires a high correlation among backscattered signals. For harmonic imaging, the spatial coherence of backscatter for the second harmonic component is different than the spatial coherence of backscatter for the fundamental component. The purpose of this work was to determine the effect of changing the transmit apodization on the spatial coherence of backscatter for the nonlinearly generated second harmonic. Our approach was to determine the effective apodizations for the fundamental and second harmonic using both experimental measurements and simulations. Two-dimensional measurements of the transverse cross sections of the finite-amplitude ultrasonic fields generated by rectangular and circular apertures were acquired with a hydrophone. Three different one-dimensional transmit apodization functions were investigated: uniform, Riesz, and trapezoidal. An effective apodization was obtained for each transmit apodization by backpropagating the values measured from within the transmit focal zone using a linear angular spectrum approach. Predictions of the spatial coherence of backscatter were obtained using the pulse-echo Van Cittert-Zernike theorem. In all cases the effective apodization at 2f was narrower than the transmit apodization. We demonstrate that certain transmit apodizations result in a greater spatial coherence of backscatter at the second harmonic than at the fundamental.

Spatial coherence of the nonlinearly generated second harmonic portion of backscatter for a clinical imaging system.

Correlation-based approaches to phase aberration correction rely on the spatial coherence of backscattered signals. The spatial coherence of backscatter from speckle-producing targets is predicted by the auto correlation of the transmit apodization (Van Cittert-Zernike theorem). Work by others indicates that the second harmonic beam has a wider mainlobe with lower sidelobes than a beam transmitted at 2f. The purpose of this paper is to demonstrate that the spatial coherence of backscatter for the second harmonic is different from that of the fundamental, as would be anticipated from applying the Van Cittert-Zernike theorem to the reported measurements of the second harmonic field. Another objective of this work is to introduce the concept of the effective apodization and to verify that the effective apodization of the second harmonic is narrower than the transmit apodization. The spatial coherence of backscatter was measured using three clinical arrays with a modified clinical imaging system. The spatial coherence results were verified using a pseudo-array scan in a transverse plane of the transmitted field with a hydrophone. An effective apodization was determined by backpropagating these values using a linear angular spectrum approach. The spatial coherence for the harmonic portion of backscatter differed systematically and significantly from the auto correlation of the transmit apodization.