Carl L. Chalek

Implementation of vibro-acoustography on a clinical ultrasound system

Vibro-acoustography (VA) is an ultrasound-based imaging modality that uses two ultrasound beams of slightly different frequencies to produce images based on the acoustic response due to harmonic ultrasound radiation force excitation at the difference frequency between the two ultrasound frequencies. VA has demonstrated feasibility and usefulness in imaging of breast and prostate tissue. However, previous studies have been performed either in controlled water tank settings or using a prototype breast scanner equipped with a water tank. In order to make VA more accessible and relevant to clinical use, we report here on the implementation of VA on a General Electric Vivid 7 ultrasound scanner. In this paper, we will describe software and hardware modifications that were performed to make VA functional on this system. We will discuss aperture definition for the two ultrasound beams and beamforming using a linear array transducer. Experimental results from beam measurements and phantom imaging studies will be shown. The implementation of VA provides a step towards clinical translation of this imaging modality for applications in various organs including breast and prostate.

Improved in vivo abdominal image quality using real-time estimation and correction of wavefront arrival time errors

The speed of sound varies with tissue type, yet commercial ultrasound imagers assume it is constant. Sound speed variation in abdominal fat and muscle layers is widely believed to be largely responsible for poor image contrast and resolution in some patients. The simplest model of the abdominal wall assumes that it adds a spatially varying time delay to the ultrasound wavefront. We describe an adaptive imaging system consisting of a GE LOGIQ 700 imager connected to a multi-processor computer. Arrival time errors for each beamforming channel, estimated by correlating each channel signal with the beamsum signal, are used to correct the imagers transmit and receive beamforming time delays at the image frame rate. A multi-row transducer provides two dimensional sampling of wavefront arrival time errors. After beamforming time delay correction, we observe significant improvement in abdominal images of healthy male volunteers, including increased contrast of blood vessels, increased brightness of liver tissue, and improved definition of the renal capsule and splenic boundary.

Automated Ultrasound Scanning on a Dual-Modality Breast Imaging System Coverage and Motion Issues and Solutions

We are developing an automated ultrasound imaging‐mammography system wherein a digital mammography unit has been augmented with a motorized ultrasound transducer carriage above a special compression paddle. Challenges of this system are acquiring complete coverage of the breast and minimizing motion. We assessed these problems and investigated methods to increase coverage and stabilize the compressed breast.

Simultaneous grayscale and subharmonic ultrasound imaging on a modified commercial scanner

OBJECTIVE To demonstrate the feasibility of simultaneous dual fundamental grayscale and subharmonic imaging on a modified commercial scanner. MOTIVATION The ability to generate signals at half the insonation frequency is exclusive to ultrasound contrast agents (UCA). Thus, subharmonic imaging (SHI; transmitting at f(0) and receiving at f(0)/2) provides improved visualization of UCA within the vasculature via suppression of the surrounding tissue echoes. While this capability has proven useful in a variety of clinical applications, the SHI suppression of surrounding tissue landmarks (which are needed for sonographic navigation) also limits it use as a primary imaging modality. In this paper we present results using a commercial ultrasound scanner modified to allow imaging in both grayscale (f(0)=4.0 MHz) and SHI (f(0)=2.5 MHz, f(0)/2=1.25 MHz) modes in real time. METHODS A Logiq 9 ultrasound scanner (GE Healthcare, Milwaukee, WI) with a 4C curvilinear probe was modified to provide this capability. Four commercially available UCA (Definity, Lantheus Medical Imaging, North Billerica, MA; Optison, GE Healthcare, Princeton, NJ; SonoVue, Bracco Imaging, Milan, Italy; and Sonazoid, GE Healthcare, Oslo, Norway) were all investigated in vitro over an acoustic output range of 3.34 MPa. In vivo the subharmonic response of Sonazoid was investigated in the portal veins of four canines (open abdominal cavity) and four patients with suspected portal hypertension. RESULTS In vitro, the four UCA showed an average maximum subharmonic amplitude of 44.1±5.4 dB above the noise floor with a maximum subharmonic amplitude of 48.6±1.6 dB provided by Sonazoid. The average in vivo maximum signal above the noise floor from Sonazoid was 20.8±2.3 dB in canines and 33.9±5.2 dB in humans. Subharmonic amplitude as a function of acoustic output in both groups matched the S-curve behavior of the agent observed in vitro. The dual grayscale imaging provided easier sonographic navigation, while the degree of tissue suppression in SHI mode varied greatly on a case by case basis. CONCLUSIONS These results demonstrate the feasibility of dual grayscale and SHI on a modified commercial scanner. The ability to simultaneously visualize both imaging modes in real time should improve the applicability of SHI as a future primary clinical imaging modality.

Chronic Liver Disease: Noninvasive Subharmonic Aided Pressure Estimation of Hepatic Venous Pressure Gradient

PURPOSE To compare subharmonic aided pressure estimation (SHAPE) with pressure catheter-based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy. MATERIALS AND METHODS This HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. RESULTS The 45 study patients included 27 men and 18 women (age range, 19-71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG ≥ 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB ± 0.61 [standard deviation] vs -1.47 dB ± 0.29, P < .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension. CONCLUSION Preliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension.

A 1.5D transducer for medical ultrasound

The current shift to digital beamforming technology holds promise for regular and rapid increases in the number of channels in a medical imager. A 1D transducer typically utilizes 125 elements, while a fully sampled two-dimensional aperture requires of order 10000 elements. Currently, channels are still expensive, so it is of interest to evaluate how much performance can be improved with a moderate increment in channel count. How may we maximize the impact on voxel size? The number of elevational elements is constrained by how complex the interconnections can become. It is impractical to significantly degrade the azimuthal resolution from the 1D case. We present beam profiles and images from a first attempt at judicious use of a 256 channel imager. Simulations and experiments allow us to explore compromises among a number of design goals. We have fabricated a transducer with several elevational rows which reduces the slice thickness of the image while maintaining full azimuthal resolution

Investigating the Efficacy of Subharmonic Aided Pressure Estimation for Portal Vein Pressures and Portal Hypertension Monitoring

The efficacy of using subharmonic emissions from Sonazoid microbubbles (GE Healthcare, Oslo, Norway) to track portal vein pressures and pressure changes was investigated in 14 canines using either slow- or high-flow models of portal hypertension (PH). A modified Logiq 9 scanner (GE Healthcare, Milwaukee, WI, USA) operating in subharmonic mode (f(transmit): 2.5 MHz, f(receive): 1.25 MHz) was used to collect radiofrequency data at 10-40% incident acoustic power levels with 2-4 transmit cycles (in triplicate) before and after inducing PH. A pressure catheter (Millar Instruments, Inc., Houston, TX, USA) provided reference portal vein pressures. At optimum insonification, subharmonic signal amplitude changes correlated with portal vein pressure changes; r ranged from -0.82 to -0.94 and from -0.70 to -0.73 for PH models considered separately or together, respectively. The subharmonic signal amplitudes correlated with absolute portal vein pressures (r: -0.71 to -0.79). Statistically significant differences between subharmonic amplitudes, before and after inducing PH, were noted (p ≤ 0.01). Portal vein pressures estimated using subharmonic aided pressure estimation did not reveal significant differences (p > 0.05) with respect to the pressures obtained using the Millar pressure catheter. Subharmonic-aided pressure estimation may be useful clinically for portal vein pressure monitoring.

Quantitative analysis of vascular heterogeneity in breast lesions using contrast-enhanced 3-D harmonic and subharmonic ultrasound imaging

Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D harmonic (HI) and subharmonic (SHI) ultrasound imaging was investigated in a clinical population. Patients (n = 134) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3-D HI, and 3-D SHI on a modified Logiq 9 scanner (GE Healthcare). A region of interest corresponding to ultrasound contrast agent flow was identified in 4D View (GE Medical Systems) and mapped to raw slice data to generate a map of time-intensity curves for the lesion volume. Time points corresponding to baseline, peak intensity, and washout of ultrasound contrast agent were identified and used to generate and compare vascular heterogeneity plots for malignant and benign lesions. Vascularity was observed with power Doppler imaging in 84 lesions (63 benign and 21 malignant). The 3-D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3-D SHI visualized flow in 68 lesions (49 benign and 19 malignant). Analysis of vascular heterogeneity in the 3-D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.71 ± 0.96 vs. 1.13 ± 0.79 dB, p <; 0.001, respectively), whereas malignant lesions showed no difference (1.66 ± 1.39 vs. 1.24 ± 1.14 dB, p = 0.24), indicative of more vascular coverage. These preliminary results suggest quantitative evaluation of vascular heterogeneity in breast lesions using contrast-enhanced 3-D SHI is feasible and able to detect variations in vascularity between central and peripheral sections for benign and malignant lesions.

On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation

Incident acoustic output (IAO) dependent subharmonic signal amplitudes from ultrasound contrast agents can be categorized into occurrence, growth or saturation stages. Subharmonic aided pressure estimation (SHAPE) is a technique that utilizes growth stage subharmonic signal amplitudes for hydrostatic pressure estimation. In this study, we developed an automated IAO optimization algorithm to identify the IAO level eliciting growth stage subharmonic signals and also studied the effect of pulse length on SHAPE. This approach may help eliminate the problems of acquiring and analyzing the data offline at all IAO levels as was done in previous studies and thus, pave the way for real-time clinical pressure monitoring applications. The IAO optimization algorithm was implemented on a Logiq 9 (GE Healthcare, Milwaukee, WI) scanner interfaced with a computer. The optimization algorithm stepped the ultrasound scanner from 0% to 100% IAO. A logistic equation fitting function was applied with the criterion of minimum least squared error between the fitted subharmonic amplitudes and the measured subharmonic amplitudes as a function of the IAO levels and the optimum IAO level was chosen corresponding to the inflection point calculated from the fitted data. The efficacy of the optimum IAO level was investigated for in vivo SHAPE to monitor portal vein (PV) pressures in 5 canines and was compared with the performance of IAO levels, below and above the optimum IAO level, for 4, 8 and 16 transmit cycles. The canines received a continuous infusion of Sonazoid microbubbles (1.5 μl/kg/min; GE Healthcare, Oslo, Norway). PV pressures were obtained using a surgically introduced pressure catheter (Millar Instruments, Inc., Houston, TX) and were recorded before and after increasing PV pressures. The experiments showed that optimum IAO levels for SHAPE in the canines ranged from 6% to 40%. The best correlation between changes in PV pressures and in subharmonic amplitudes (r=-0.76; p=0.24), and between the absolute PV pressures and the subharmonic amplitudes (r=-0.89; p<0.01) were obtained for the optimized IAO and 4 transmit cycles. Only for the optimized IAO and 4 transmit cycles did the subharmonic amplitudes differ significantly (p<0.01) before and after increasing PV pressures. A new algorithm to identify optimum IAO levels for SHAPE has been developed and validated with the best results being obtained for 4 transmit cycles. The work presented in this study may pave the way for real-time clinical applications of estimating pressures using the subharmonic signals from ultrasound contrast agents.

A beamforming study for implementation of vibro-acoustography with a 1.75-D array transducer

Vibro-acoustography (VA) is an ultrasoundbased imaging modality that uses radiation force produced by two cofocused ultrasound beams separated by a small frequency difference, Δf, to vibrate tissue at Δf. An acoustic field is created by the object vibration and measured with a nearby hydrophone. This method has recently been implemented on a clinical ultrasound system using 1-D linear-array transducers. In this article, we discuss VA beamforming and image formation using a 1.75-D array transducer. A 1.75-D array transducer has several rows of elements in the elevation direction which can be controlled independently for focusing. The advantage of the 1.75-D array over a 1-D linear-array transducer is that multiple rows of elements can be used for improving elevation focus for imaging formation. Six configurations for subaperture design for the two ultrasound beams necessary for VA imaging were analyzed. The point-spread functions for these different configurations were evaluated using a numerical simulation model. Four of these configurations were then chosen for experimental evaluation with a needle hydrophone as well as for scanning two phantoms. Images were formed by scanning a urethane breast phantom and an ex vivo human prostate. VA imaging using a 1.75-D array transducer offers several advantages over scanning with a linear-array transducer, including improved image resolution and contrast resulting from better elevation focusing of the imaging point-spread function.