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 6 0.61 [standard deviation] vs 21.47 dB 6 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.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

Vibro-acoustography 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. Vibro-acoustography 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 a prototype breast scanner equipped with a water tank. In order to make vibro-acoustography more accessible and relevant to clinical use, we report here on the implementation of vibro-acoustography on a General Electric Vivid 7 ultrasound scanner. In this paper, we will describe software and hardware modifications that were performed to make vibro-acoustography 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 vibro-acoustography provides a step towards clinical translation of this imaging modality for applications in various organs including breast, prostate, thyroid, kidney, and liver.

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 f0 and receiving at f0/2) 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 (f0 = 4.0 MHz) and SHI (f0 = 2.5 MHz, f0/2 = 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 (GE Healthcare, Oslo, Norway) was investigated in the portal veins of 4 canines (open abdominal cavity) and 4 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 if 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.

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) operating in subharmonic mode (ftransmit:2.5MHz, freceive:1.25MHz) was used to collect RF 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) 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 SHAPE 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.

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 Author Manuscript 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. HHS Public Access