Effect of Pulse Shaping on Subharmonic Aided Pressure Estimation In Vitro and In Vivo.

OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz radio-frequency data. Scanning was performed in dual imaging mode with B-mode imaging at 4 MHz and a SHI contrast mode transmitting at 2.5 MHz and receiving at 1.25 MHz. Sonazoid, which is a lipid stabilized gas filled bubble of perfluorobutane, was used as the contrast agent in this study. RESULTS: A linear decrease in subharmonic amplitude with increased pressure was observed for all waveforms (r from -0.77 to -0.93; P \u3c .001) in vitro. There was a significantly higher correlation of the SHAPE gradient with changing pressures for the broadband pulses as compared to the narrowband pulses in both in vitro and in vivo results. The highest correlation was achieved with a Gaussian windowed binomial filtered square wave with an r-value of -0.95. One of the three canines was eliminated for technical reasons, while the other two produced very similar results to those obtained in vitro (r from -0.72 to -0.98; P CONCLUSIONS: Using this waveform is an improvement to the existing SHAPE technique (where a square wave was used) and should make SHAPE more sensitive for noninvasively determining portal hypertension

The Performance of Flash Replenishment Contrast-Enhanced Ultrasound for the Qualitative Assessment of Kidney Lesions in Patients with Chronic Kidney Disease

We investigated the accuracy of CEUS for characterizing cystic and solid kidney lesions in patients with chronic kidney disease (CKD). Cystic lesions are assessed using Bosniak criteria for computed tomography (CT) and magnetic resonance imaging (MRI); however, in patients with moderate to severe kidney disease, CT and MRI contrast agents may be contraindicated. Contrast-enhanced ultrasound (CEUS) is a safe alternative for characterizing these lesions, but data on its performance among CKD patients are limited. We performed flash replenishment CEUS in 60 CKD patients (73 lesions). Final analysis included 53 patients (63 lesions). Four readers, blinded to true diagnosis, interpreted each lesion. Reader evaluations were compared to true lesion classifications. Performance metrics were calculated to assess malignant and benign diagnoses. Reader agreement was evaluated using Bowker’s symmetry test. Combined reader sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignant lesions were 71%, 75%, 45%, and 90%, respectively. Sensitivity (81%) and specificity (83%) were highest in CKD IV/V patients when grouped by CKD stage. Combined reader sensitivity, specificity, PPV, and NPV for diagnosing benign lesions were 70%, 86%, 91%, and 61%, respectively. Again, in CKD IV/V patients, sensitivity (81%), specificity (95%), and PPV (98%) were highest. Inter-reader diagnostic agreement varied from 72% to 90%. In CKD patients, CEUS is a potential low-risk option for screening kidney lesions. CEUS may be particularly beneficial for CKD IV/V patients, where kidney preservation techniques are highly relevant

Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imaging in vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging

Four-Dimensional (4D) Subharmonic Aided Pressure Estimation for Monitoring Neoadjuvant Chemotherapy Response of Breast Cancer

Introduction Neoadjuvant chemotherapy is a well-established treatment option for patients with non-metastatic breast cancer. The patient response is correlated with survival. However, the optimal method for monitoring neoadjuvant therapy response has not been established. One factor that may affect the response of neoadjuvant therapy is the interstitial fluid pressure (IFP). Increased IFP prevents an effective delivery of therapeutic agents and reduces the efficacy of the therapy. Recently, subharmonic-aided pressure estimation (SHAPE) using contrast-enhanced ultrasound (CEUS) has been developed and its potential was demonstrated in animals as a non-invasive technique for IFP measurements. The SHAPE method estimates IFP based on the inverse relationship between the subharmonic signal magnitude from CEUS and IFP. The purpose of this study was to determine if 4D SHAPE can predict the response of breast cancer to neoadjuvant chemotherapy. Poster presented at International Ultrasonics Symposium in Tours France.https://jdc.jefferson.edu/radiologyposters/1001/thumbnail.jp

3D Harmonic and Subharmonic Imaging for Characterizing Breast Lesions: A Multi-Center Clinical Trial.

OBJECTIVE: Breast cancer is the most frequent type of cancer among women. This multi-center study assessed the ability of 3D contrast-enhanced ultrasound to characterize suspicious breast lesions using clinical assessments and quantitative parameters. METHODS: Women with suspicious breast lesions scheduled for biopsy were enrolled in this prospective, study. Following 2D grayscale ultrasound and power Doppler imaging (PDI), a contrast agent (Definity; Lantheus) was administrated. Contrast-enhanced 3D harmonic imaging (HI; transmitting/receiving at 5.0/10.0 MHz), as well as 3D subharmonic imaging (SHI; transmitting/receiving at 5.8/2.9 MHz), were performed using a modified Logiq 9 scanner (GE Healthcare). Five radiologists independently scored the imaging modes (including standard-of-care imaging) using a 7-point BIRADS scale as well as lesion vascularity and diagnostic confidence. Parametric volumes were constructed from time-intensity curves for vascular heterogeneity, perfusion, and area under the curve. Diagnostic accuracy was determined relative to pathology using receiver operating characteristic (ROC) and reverse, step-wise logistical regression analyses. The κ-statistic was calculated for inter-reader agreement. RESULTS: Data were successfully acquired in 219 cases and biopsies indicated 164 (75%) benign and 55 (25%) malignant lesions. SHI depicted more anastomoses and vascularity than HI (P < .021), but there were no differences by pathology (P > .27). Ultrasound achieved accuracies of 82 to 85%, which was significantly better than standard-of-care imaging (72%; P < .03). SHI increased diagnostic confidence by 3 to 6% (P < .05), but inter-reader agreements were medium to low (κ < 0.52). The best regression model achieved 97% accuracy by combining clinical reads and parametric SHI. CONCLUSIONS: Combining quantitative 3D SHI parameters and clinical assessments improves the characterization of suspicious breast lesions

Characterizing Breast Lesions Using Quantitative Parametric 3D Subharmonic Imaging: A Multicenter Study

Rationale and objectivesBreast cancer is the leading type of cancer among women. Visualization and characterization of breast lesions based on vascularity kinetics was evaluated using three-dimensional (3D) contrast-enhanced ultrasound imaging in a clinical study.Materials and methodsBreast lesions (n = 219) were imaged using power Doppler imaging (PDI), 3D contrast-enhanced harmonic imaging (HI), and 3D contrast-enhanced subharmonic imaging (SHI) with a modified Logiq 9 ultrasound scanner using a 4D10L transducer. Quantitative metrics of vascularity derived from 3D parametric volumes (based on contrast perfusion; PER and area under the curve; AUC) were generated by off-line processing of contrast wash-in and wash-out. Diagnostic accuracy of these quantitative vascular parameters was assessed with biopsy results as the reference standard.ResultsVascularity was observed with PDI in 93 lesions (69 benign and 24 malignant), 3D HI in 8 lesions (5 benign and 3 malignant), and 3D SHI in 83 lesions (58 benign and 25 malignant). Diagnostic accuracy for vascular heterogeneity, PER, and AUC ranged from 0.52 to 0.75, while the best logistical regression model (vascular heterogeneity ratio, central PER, and central AUC) reached 0.90.Conclusion3D SHI successfully detects contrast agent flow in breast lesions and characterization of these lesions based on quantitative measures of vascular heterogeneity and 3D parametric volumes is promising

Pulse Shaping for Improved Diagnosis of Portal Hypertension Using Subharmonic Aided Pressure Estimation

Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of contrast microbubbles (obtained by transmitting at the fundamental frequency fo and receiving at fo/2) and the ambient pressure (see fig.1). A noninvasive ultrasound based pressure estimation procedure would be a major development in the diagnosis of portal hypertension and less invasive than the current catheter-based hepatic venous pressure gradient (HVPG) measurement. The hypothesis of this study was that portal vein pressures can be monitored and quantified noninvasively in humans using SHAPE. First selected waveforms were optimized in vitro and in canines, then SHAPE was correlated with measured HVPG in patients undergoing a transjugular liver biopsy (TJLB).https://jdc.jefferson.edu/radiologyposters/1004/thumbnail.jp