Acoustic diffraction-resistant adaptive profile technology (ADAPT) for elasticity imaging.

Acoustic beam shaping with high degrees of freedom is critical for applications such as ultrasound imaging, acoustic manipulation, and stimulation. However, the ability to fully control the acoustic pressure profile over its propagation path has not yet been achieved. Here, we demonstrate an acoustic diffraction-resistant adaptive profile technology (ADAPT) that can generate a propagation-invariant beam with an arbitrarily desired profile. By leveraging wave number modulation and beam multiplexing, we develop a general framework for creating a highly flexible acoustic beam with a linear array ultrasonic transducer. The designed acoustic beam can also maintain the beam profile in lossy material by compensating for attenuation. We show that shear wave elasticity imaging is an important modality that can benefit from ADAPT for evaluating tissue mechanical properties. Together, ADAPT overcomes the existing limitation of acoustic beam shaping and can be applied to various fields, such as medicine, biology, and material science.

Ultrasonic Sound Speed Estimation for Liver Fat Quantification: A Review by the AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

Non-alcoholic fatty liver disease (NAFLD) is a significant cause of diffuse liver disease, morbidity and mortality worldwide. Early and accurate diagnosis of NALFD is critical to identify patients at risk of disease progression. Liver biopsy is the current gold standard for diagnosis and prognosis. However, a non-invasive diagnostic tool is desired because of the high cost and risk of complications of tissue sampling. Medical ultrasound is a safe, inexpensive and widely available imaging tool for diagnosing NAFLD. Emerging sonographic tools to quantitatively estimate hepatic fat fraction, such as tissue sound speed estimation, are likely to improve diagnostic accuracy, precision and reproducibility compared with existing qualitative and semi-quantitative techniques. Various pulse-echo ultrasound speed of sound estimation methodologies have been investigated, and some have been recently commercialized. We review state-of-the-art in vivo speed of sound estimation techniques, including their advantages, limitations, technical sources of variability, biological confounders and existing commercial implementations. We report the expected range of hepatic speed of sound as a function of liver steatosis and fibrosis that may be encountered in clinical practice. Ongoing efforts seek to quantify sound speed measurement accuracy and precision to inform threshold development around meaningful differences in fat fraction and between sequential measurements.

Experimental Validation of Longitudinal Speed of Sound Estimates in the Diagnosis of Hepatic Steatosis (Part II).

This study validates a non-invasive, quantitative technique to diagnose steatosis within tissue. The proposed method is based on two fundamental concepts: (i) the speed of sound in a fatty liver is lower than that in a healthy liver and (ii) the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the speed in the medium under examination. The method uses image brightness and sharpness as quantitative image-quality metrics to predict the true sound speed and capture the effects of fat infiltration, while accounting for the transmission through subcutaneous fat. Ex vivo testing on sheep liver, mouse livers and tissue-mimicking phantoms indicated the technique's ability to predict the true speed of sound with errors less than 0.5% and to quantify the inverse correlation between fat content and speed of sound.

Quantitative Hepatic Fat Quantification in Non-alcoholic Fatty Liver Disease Using Ultrasound-Based Techniques: A Review of Literature and Their Diagnostic Performance.

Non-alcoholic fatty liver disease is a condition that is characterized by the presence of >5% fat in the liver and affects more than one billion people worldwide. If adequate and early precautions are not taken, non-alcoholic fatty liver disease can progress to cirrhosis and death. The current reference standard for detecting hepatic steatosis is a liver biopsy. However, because of the potential morbidity associated with liver biopsies, non-invasive imaging biomarkers have been extensively investigated. Magnetic resonance imaging-based methods have proven accuracy in quantifying liver steatosis; however, these techniques are costly and have limited availability. Ultrasound-based quantitative imaging techniques are increasingly utilized because of their widespread availability, ease of use and relative cost-effectiveness. Several ultrasound-based liver fat quantification techniques have been investigated, including techniques that measure changes in the acoustic properties of the liver caused by the presence of fat. In this review, we focus on quantitative ultrasound approaches and their diagnostic performance in the realm of non-alcoholic fatty liver disease.

Surgery for Obesity and Related Diseases: I. A Novel Approach to the Quantification of the Longitudinal Speed of Sound and Its Potential for Tissue Characterization.

Described here is a method to determine the longitudinal speed of sound in speckle-dominated ultrasound images. The method is based on the concept that the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the speed in the medium. The method captures the quality of the ultrasound image using two quantitative image-quality metrics: image brightness and sharpness around the intended focal zone. The proposed method requires no calibration, is computationally efficient and is deployable on commercial ultrasound systems without hardware or software modifications. Ex vivo testing on tissue-mimicking phantoms indicates the method's accuracy in predicting the true speed of sound to within 1% of ground truth values.

A Column-Row-Parallel Ultrasound Imaging Architecture for 3D Plane-wave Imaging and Tx 2nd-Order Harmonic Distortion (HD2) Reduction.

We propose a Column-Row-Parallel imaging frontend architecture for integrated and low-power 3D medical ultrasound imaging. The Column-Row-Parallel architecture offers linear-scaling interconnection, acquisition and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data / control interface to a 2D array. A 16×16 CMUT-ASIC Column-Row-Parallel prototype is fabricated and assembled with a flip-chip bonding process. It facilitates the 3D plane-wave coherent compounding algorithm for volumetric imaging with a fast frame rate of 62.5 Hz and 46% improved lateral resolution with 10-angle compounding and a field of view volume of 2.3mm in both azimuth and elevation, 8.5mm in depth. At a hypothetically scaled up 64x64 array size, the frame rate can still be kept at 31.2 Hz for a volume of 40mm in both azimuth and elevation, 150mm in depth. An interleaved checker board pattern with in-phase (I) and quadrature (Q) excitations is also demonstrated for reducing CMUT second harmonic distortion (HD2) emission by up to 25 dB at the loss of 3 dB fundamental energy reduction. The method reduces nonlinear effects from both transducers and circuits and is a wide band technique that is applicable to arbitrary pulse shapes.

A Column-Row-Parallel Ultrasound Imaging Architecture for 3-D Plane-Wave Imaging and Tx Second-Order Harmonic Distortion Reduction.

We propose a column-row-parallel imaging front-end architecture for integrated and low-power 3-D medical ultrasound imaging. The column-row-parallel architecture offers linear-scaling interconnection, acquisition, and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data/control interface to a 2-D array. A capacitive micromachined ultrasonic transducer (CMUT)-application-specific integrated circuit (ASIC) column-row-parallel prototype is fabricated and assembled with a flip-chip bonding process. It facilitates the 3-D plane-wave coherent compounding algorithm for volumetric imaging with a fast frame rate of 62.5 Hz and 46% improved lateral resolution with 10-angle compounding and a field of view volume of 2.3 mm in both azimuth and elevation, 8.5 mm in depth. At a hypothetically scaled up array size, the frame rate can still be kept at 31.2 Hz for a volume of 40 mm in both azimuth and elevation, 150 mm in depth. An interleaved checkerboard pattern with in-phase ( ) and quadrature ( ) excitations is also demonstrated for reducing CMUT second-harmonic distortion emission by up to 25 dB at the loss of 3-dB fundamental energy reduction. The method reduces nonlinear effects from both transducers and circuits and is a wide band technique that is applicable to arbitrary pulse shapes.

Non-invasive diagnosis of non-alcoholic fatty liver disease (NAFLD) using ultrasound image echogenicity.

This paper introduces a non-invasive, quantitative technique to diagnose the progression of non-alcoholic fatty liver disease (NAFLD). The method is predicated on two fundamental principles: 1) the speed of sound in a fatty liver is lower than that in a healthy liver and 2) the quality of an ultrasound image is maximized when the beamformer's speed of sound matches the true speed of sound in the tissue being examined. The proposed method uses the echogenicity of an ultrasound image as a quantitative measure to estimate the true speed of sound within the liver parenchyma and capture its correlation with the underlying fat content. The proposed technique was evaluated in simulations and then tested ex vivo on sheep liver, mice liver (healthy and fatty) and tissue-mimicking phantoms. In the case of the phantom and sheep liver, the method was able to estimate the true speed of sound with errors of less than 0.5%; in the case of the mice livers, the method was able to accurately estimate the speed of sound within the livers (less than 1% error) and capture the correlation between fat content and speed of sound. Thereby, demonstrating the capability of ultrasound technology to non-invasively, quantitatively, and accurately diagnose NAFLD at point of care.

Automated Breast Ultrasound: Dual-Sided Compared with Single-Sided Imaging.

The design and performance of a mammographically configured, dual-sided, automated breast ultrasound (ABUS) 3-D imaging system are described. Dual-sided imaging (superior and inferior) is compared with single-sided imaging to aid decisions on clinical implementation of the more complex, but potentially higher-quality dual-sided imaging. Marked improvement in image quality and coverage of the breast is obtained in dual-sided ultrasound over single-sided ultrasound. Among hypo-echoic masses imaged, there are increases in the mean contrast-to-noise ratio of 57% and 79%, respectively, for spliced dual-sided versus superior or inferior single-sided imaging. The fractional breast volume coverage, defined as the percentage volume in the transducer field of view that is imaged with clinically acceptable quality, is improved from 59% in both superior and inferior single-sided imaging to 89% in dual-sided imaging. Applying acoustic coupling to the breast requires more effort or sophisticated methods in dual-sided imaging than in single-sided imaging.

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.

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.

Reconfigurable mosaic annular arrays.

Mosaic annular arrays (MAA) based on reconfigurable array (RA) transducer electronics assemblies are presented as a potential solution for future highly integrated ultrasonic transducer subsystems. Advantages of MAAs include excellent beam quality and depth of field resulting from superior elevational focus compared with 1-D electronically scanned arrays, as well as potentially reduced cost, size, and power consumption resulting from the use of a limited number of beamforming channels for processing a large number of subelements. Specific design tradeoffs for these highly integrated arrays are discussed in terms of array specifications for center frequency, element pitch, and electronic switch-on resistance. Large-area RAs essentially function as RC delay lines. Efficient architectures which take into account RC delay effects are presented. Architectures for integration of the transducer and electronics layers of large-area array implementations are reviewed.

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

OBJECTIVES: 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. MATERIALS AND METHODS: A LOGIQ™ 9 scanner (GE Healthcare, Milwaukee, WI) equipped with a 4D10L probe was modified to perform 3D harmonic imaging (HI; f(transmit), 5 MHz and f(receive), 10 MHz) and subharmonic imaging (SHI; f(transmit), 5.8 MHz and f(receive), 2.9 MHz). In vivo imaging was performed in the lower pole of both kidneys in 5 open-abdomen canines after injection of the ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, MA). The canines received a 5-µL/kg bolus injection of Definity for HI and a 20-µL/kg bolus for SHI in triplicate for each kidney. Ultrasound data acquisition was started just before the injection of UCA (to capture the wash-in) and continued until washout. A microvascular staining technique based on stable (nonradioactive) isotope-labeled microspheres (Biophysics Assay Laboratory, Inc, Worcester, MA) was used to quantify the degree of perfusion in each kidney (the reference standard). Ligating a surgically exposed branch of the renal arteries induced lower perfusion rates. This was followed by additional contrast-enhanced imaging and microsphere injections to measure post-ligation perfusion. Slice data were extracted from the 3D ultrasound volumes and used to generate time-intensity curves offline in the regions corresponding to the tissue samples used for microvascular staining. The midline plane was also selected from the 3D volume (as a quasi-2-dimensional [2D] image) and compared with the 3D imaging modes. Perfusion was estimated from the initial slope of the fractional blood volume uptake (for both HI and SHI) and compared with the reference standard using linear regression analysis. RESULTS: Both 3D HI and SHI were able to provide visualization of flow and, thus, perfusion in the kidneys. However, SHI provided near-complete tissue suppression and improved visualization of the UCA flow. Microsphere perfusion data were available for 4 canines (1 was excluded because of an error with the reference blood sample) and showed a mean (SD) perfusion of 9.30 (6.60) and 5.15 (3.42) mL/min per gram before and after the ligation, respectively. The reference standard showed significant correlation with the overall 3D HI perfusion estimates (r = 0.38; P = 0.007), but it correlated more strongly with 3D SHI (r = 0.62; P < 0.001). In addition, these results showed an improvement over the quasi-2D HI and SHI perfusion estimates (r = -0.05 and r = 0.14) and 2D SHI perfusion estimates previously reported by our group (r = 0.57). CONCLUSIONS: In this preliminary study, 3D contrast-enhanced nonlinear ultrasound was able to quantify perfusion in vivo. Three-dimensional SHI resulted in better overall agreement with the reference standard than 3D HI did and was superior to previously reported 2D SHI results. Three-dimensional SHI outperforms the other methods for estimating blood perfusion because of the improved visualization of the complete perfused vascular networks.

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

Vibro-acoustography (VA) is an ultrasound-based 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.

Packaging and modular assembly of large-area and fine-pitch 2-D ultrasonic transducer arrays.

A promising transducer architecture for largearea arrays employs 2-D capacitive micromachined ultrasound transducer (CMUT) devices with backside trench-frame pillar interconnects. Reconfigurable array (RA) application-specified integrated circuits (ASICs) can provide efficient interfacing between these high-element-count transducer arrays and standard ultrasound systems. Standard electronic assembly techniques such as flip-chip and ball grid array (BGA) attachment, along with organic laminate substrate carriers, can be leveraged to create large-area arrays composed of tiled modules of CMUT chips and interface ASICs. A large-scale, fully populated and integrated 2-D CMUT array with 32 by 192 elements was developed and demonstrates the feasibility of these techniques to yield future large-area arrays. This study demonstrates a flexible and reliable integration approach by successfully combining a simple under-bump metallization (UBM) process and a stacked CMUT/interposer/ASIC module architecture. The results show high shear strength of the UBM (26.5 g for 70-µm balls), high interconnect yield, and excellent CMUT resonance uniformity (s = 0.02 MHz). A multi-row linear array was constructed using the new CMUT/interposer/ASIC process using acoustically active trench-frame CMUT devices and mechanical/ nonfunctional Si backside ASICs. Imaging results with the completed probe assembly demonstrate a functioning device based on the modular assembly architecture.

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.

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

RATIONALE AND OBJECTIVES: 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. MATERIALS AND METHODS: Three-dimensional HI and SHI were implemented on a Logiq 9 ultrasound scanner with a 4D10L probe. Four-cycle SHI was implemented to transmit at 5.8 MHz and receive at 2.9 MHz, while two-cycle HI was implemented to transmit at 5 MHz and receive at 10 MHz. The ultrasound contrast agent Definity was imaged within a flow phantom and the lower pole of two canine kidneys in both HI and SHI modes. Contrast-to-tissue ratios and rendered images were compared offline. RESULTS: SHI resulted in significant improvement in contrast-to-tissue ratios relative to HI both in vitro (12.11 ± 0.52 vs 2.67 ± 0.77, P< .001) and in vivo (5.74 ± 1.92 vs 2.40 ± 0.48, P = .04). Rendered 3D subharmonic images provided better tissue suppression and a greater overall view of vessels in a flow phantom and canine renal vasculature. CONCLUSIONS: The successful implementation of SHI in 3D allows imaging of vascular networks over a heterogeneous sample volume and should improve future diagnostic accuracy. Additionally, 3D SHI provides improved contrast-to-tissue ratios relative to 3D HI.

First in vivo use of a capacitive micromachined ultrasound transducer array-based imaging and ablation catheter.

OBJECTIVES: The primary objective was to test in vivo for the first time the general operation of a new multifunctional intracardiac echocardiography (ICE) catheter constructed with a microlinear capacitive micromachined ultrasound transducer (ML-CMUT) imaging array. Secondarily, we examined the compatibility of this catheter with electroanatomic mapping (EAM) guidance and also as a radiofrequency ablation (RFA) catheter. Preliminary thermal strain imaging (TSI)-derived temperature data were obtained from within the endocardium simultaneously during RFA to show the feasibility of direct ablation guidance procedures. METHODS: The new 9F forward-looking ICE catheter was constructed with 3 complementary technologies: a CMUT imaging array with a custom electronic array buffer, catheter surface electrodes for EAM guidance, and a special ablation tip, that permits simultaneous TSI and RFA. In vivo imaging studies of 5 anesthetized porcine models with 5 CMUT catheters were performed. RESULTS: The ML-CMUT ICE catheter provided high-resolution real-time wideband 2-dimensional (2D) images at greater than 8 MHz and is capable of both RFA and EAM guidance. Although the 24-element array aperture dimension is only 1.5 mm, the imaging depth of penetration is greater than 30 mm. The specially designed ultrasound-compatible metalized plastic tip allowed simultaneous imaging during ablation and direct acquisition of TSI data for tissue ablation temperatures. Postprocessing analysis showed a first-order correlation between TSI and temperature, permitting early development temperature-time relationships at specific myocardial ablation sites. CONCLUSIONS: Multifunctional forward-looking ML-CMUT ICE catheters, with simultaneous intracardiac guidance, ultrasound imaging, and RFA, may offer a new means to improve interventional ablation procedures.

Subharmonic contrast microbubble signals for noninvasive pressure estimation under static and dynamic flow conditions.

Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60 degree angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0-186 mmHg, acoustic pressures from 0.35-0.60 MPa peak-to-peak and frequencies of 2.5-6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9-14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5-4.5 MHz and acoustic pressures from 0-3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.