contrast-enhanced-subharmonic-aided-pressure-estimation-shape-using

Contrast-Enhanced Subharmonic Aided Pressure Estimation (SHAPE) Using Ultrasound Imaging with a Focus on Identifying Portal Hypertension

Noninvasive, accurate measurement of pressures within the human body has long been an important but elusive clinical goal. Contrast agents for ultrasound ...

GE Global Research

The combination of sensitive magnetic resonance techniques with a selective site-targeted nanoparticle contrast agent has a demonstrated utility for molecular imaging studies. By detecting a unique signature of the contrast agent, this approach can be employed to identify specific bio-molecular markers and observe cellular-level processes within a large and complex organism (e.g., in vivo rabbit). The objective of the present investigation was to design, fabricate and characterize a radio-frequency (RF) coil for the dual frequency ((1)H and (19)F) simultaneous collection of both nuclei images in a 3T field, in order to facilitate studies of arthritic knee degradation in rabbits. The coil supports both transmit and receive modes. The supporting activities included: 1) establishing a technical database for calculating the required coil parameters, 2) selection of a favorable coil geometry, and 3) adaption of existing RF measurement techniques to the design, development and electrical evaluation of the coil. The coil is used in conjunction with a Philips Medical Systems clinical MRI scanner, requiring all RF simultaneous dual frequency ((1)H and (19)F) coils to operate in both transmit and receive modes. A commercial version of SPICE (simulation program with integrated circuit emphasis) was used to estimate significant operational parameters prior to fabricating the imaging coil. Excellent images were obtained with the fabricated coil and no operational problems were observed that would limit the use of other coil geometries and field strengths.

Simultaneous dual frequency 1H and 19F open coil imaging of arthritic rabbit knee at 3T.

Although contrast-enhanced ultrasound imaging techniques such as harmonic imaging (HI) have evolved to reduce tissue signals using the nonlinear properties of the contrast agent, levels of background suppression have been mixed. Subharmonic imaging (SHI) offers near complete tissue suppression by centering the receive bandwidth at half the transmitting frequency. The aims of this study were to demonstrate the feasibility of three-dimensional (3D) SHI and to compare it to 3D HI.

Three-dimensional subharmonic ultrasound imaging in vitro and in vivo.

The ability to estimate tissue perfusion (in milliliter per minute per gram) in vivo using contrast-enhanced 3-dimensional (3D) harmonic and subharmonic ultrasound imaging was investigated.

Perfusion estimation using contrast-enhanced 3-dimensional subharmonic ultrasound imaging: an in vivo study.

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.

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

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.

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

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. 

Toward 3-D Echocardiographic Determination of Regional Myofiber Structure.

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 and receiving at half the transmit frequency (ie, f /2). Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of the microbubbles and the ambient pressure change.

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

Subharmonic-aided pressure estimation (SHAPE) estimates hydrostatic pressure using the inverse relationship with subharmonic amplitude variations of ultrasound contrast agents (UCAs). We studied the impact of varying incident acoustic outputs (IAO), UCA concentration, and hematocrit on SHAPE. A Logiq 9 scanner with a 4C curvilinear probe (GE, Milwaukee, Wisconsin) was used with Sonazoid (GE Healthcare, Oslo, Norway) transmitting at 2.5 MHz and receiving at 1.25 MHz. An improved IAO selection algorithm provided improved correlations ( r from -0.85 to -0.95 vs. -0.39 to -0.98). There was no significant change in SHAPE gradient as the pressure increased from 10 to 40 mmHg and hematocrit concentration was tripled from 1.8 to 4.5 mL/L (Δ0.00-0.01 dB, p = 0.18), and as UCA concentration was increased from 0.2 to 1.2 mL/L (Δ0.02-0.05 dB, p = 0.75). The results for the correlation between the SHAPE gradient and hematocrit values for patients ( N = 100) in an ongoing clinical trial were also calculated showing a poor correlation value of 0.14. Overall, the SHAPE gradient is independent of hematocrit and UCA concentration. An improved algorithm for IAO selection will make SHAPE more accurate.

On Factors Affecting Subharmonic-aided Pressure Estimation (SHAPE).

Tools for noninvasively modulating neural signaling in peripheral organs will advance the study of nerves and their effect on homeostasis and disease. Herein, we demonstrate a noninvasive method to modulate specific signaling pathways within organs using ultrasound (U/S). U/S is first applied to spleen to modulate the cholinergic anti-inflammatory pathway (CAP), and US stimulation is shown to reduce cytokine response to endotoxin to the same levels as implant-based vagus nerve stimulation (VNS). Next, hepatic U/S stimulation is shown to modulate pathways that regulate blood glucose and is as effective as VNS in suppressing the hyperglycemic effect of endotoxin exposure. This response to hepatic U/S is only found when targeting specific sub-organ locations known to contain glucose sensory neurons, and both molecular (i.e. neurotransmitter concentration and cFOS expression) and neuroimaging results indicate US induced signaling to metabolism-related hypothalamic sub-nuclei. These data demonstrate that U/S stimulation within organs provides a new method for site-selective neuromodulation to regulate specific physiological functions.

Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation.

This pilot study evaluated whether contrast-enhanced subharmonic imaging (SHI) could be used to characterize adnexal masses before surgical intervention.

Characterization of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study.

Breast 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.

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

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation.

Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student  test. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44;  < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements ( = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020  See also the editorial by Kiessling in this issue.

Article	Year
Simultaneous dual frequency 1H and 19F open coil imaging of arthritic rabbit knee at 3T. IEEE transactions on medical imaging\| PubMed ID: 20699209	2011
Three-dimensional subharmonic ultrasound imaging in vitro and in vivo. Academic radiology\| PubMed ID: 22464198	2012
Perfusion estimation using contrast-enhanced 3-dimensional subharmonic ultrasound imaging: an in vivo study. Investigative radiology\| PubMed ID: 23695085	2013
Quantitative analysis of vascular heterogeneity in breast lesions using contrast-enhanced 3-D harmonic and subharmonic ultrasound imaging. IEEE transactions on ultrasonics, ferroelectrics, and frequency control\| PubMed ID: 25935933	2015
Therapeutic ultrasound: Increased HDL-Cholesterol following infusions of acoustic microspheres and apolipoprotein A-I plasmids. Atherosclerosis\| PubMed ID: 25969892	2015
Toward 3-D Echocardiographic Determination of Regional Myofiber Structure. Ultrasound in medicine & biology\| PubMed ID: 26589530	2016
Effect of Pulse Shaping on Subharmonic Aided Pressure Estimation In Vitro and In Vivo. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine\| PubMed ID: 27943411	2017
On Factors Affecting Subharmonic-aided Pressure Estimation (SHAPE). Ultrasonic imaging\| PubMed ID: 30417745	2019
Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation. Nature communications\| PubMed ID: 30862827	2019
Characterization of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine\| PubMed ID: 31769529	2020
Characterizing Breast Lesions Using Quantitative Parametric 3D Subharmonic Imaging: A Multicenter Study. Academic radiology\| PubMed ID: 31859210	2020
Author Correction: Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation. Nature communications\| PubMed ID: 32152308	2020
Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent. Radiology\| PubMed ID: 33201789	2020

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