3-D Ultrasound Imaging Using Helicoid Array Transducers.

Real-time 3-D intracardiac echocardiography (ICE) can enable faster imaging of surfaces orthogonal to the transducer, such as the pulmonary vein (PV) antra and cardiac valve annuli. However, the requirement for a 2-D grid of individually wired elements makes a traditional matrix array challenging to implement within an intravenous catheter. Helicoid array transducers are linear array transducers twisted about their long axis, allowing imaging of different elevation slices using sub-apertures. In this work, we examined the 3-D imaging characteristics of helicoid array transducers through simulations using Field II software and experimental measurements. We report results for varying transducer parameters, such as twist rate and sub-aperture size. We also discuss design considerations for these imaging parameters as they pertain to volumetric imaging of the heart.

Measuring Intraventricular Pressure Using Ultrasound Elastography.

OBJECTIVES: Intraventricular pressure (IVP) is one of the most important measurements for evaluating cardiac function, but this measurement is not currently easily assessable in the clinic. The primary reason for this is the absence of a noninvasive technique for measuring IVP. In this study, we investigate the relationship between IVP and dynamic myocardial stiffness measured by shear wave elasticity imaging (SWEI) and assess the feasibility of measuring IVP using SWEI. METHODS: In 8 isolated working rabbit hearts, IVP was recorded in the left ventricle using a pressure catheter. Simultaneously, myocardial stiffness was recorded by SWEI. Using the peak values for IVP and SWEI measured stiffness, SWEI measurements were calibrated and converted to IVP. RESULTS: A linear relationship with zero intercept was observed between IVP and SWEI, with the average slope of 0.318 kPa/mm Hg, R2 = 0.89. Using one point on the IVP/SWEI curve, SWEI measurements were converted to IVP. Estimated pressure using SWEI and IVP were linearly correlated with the slope of 0.95, R2 = 0.88 (mean end diastolic pressure by pressure catheter = 12.716 mm Hg and by SWEI=14.726 mm Hg), indicating the near equivalence of the 2 measurements. CONCLUSION: We have shown that SWEI measurements are linearly related to IVP; therefore, pressure-based indices could potentially be derived from SWEI ultrasound elastography. The feasibility of using SWEI to estimate IVP with a single point calibration was also shown in this study.

Assessment of Diastolic Function Using Ultrasound Elastography.

Shear wave elasticity imaging (SWEI) is a novel ultrasound elastography technique for assessing tissue stiffness. In this study, we investigate the potential of SWEI for providing diastolic functional assessment. In 11 isolated rabbit hearts, pressure-volume (PV) measurements were recorded simultaneously with SWEI recordings from the left ventricle free wall before and after induction of global ischemia. PV-based end diastolic stiffness increased by 100% after ischemia (p <0.05), and SWEI stiffness showed an increase of 103% (p <0.05). The relaxation time constant (τ) before and after ischemia derived from pressure and SWEI curves showed increases of 79% and 76%, respectively (p <0.05). A linear regression between pressure-derived and SWEI-based (τ) showed a slope of 1.164 with R2 = 0.80, indicating the near equivalence of the two assessments. SWEI can be used to derive (τ) values and myocardial end diastolic stiffness. In global conditions, these measurements are consistent with PV measurements of diastolic function.

Quantifying Myocardial Contractility Changes Using Ultrasound-Based Shear Wave Elastography.

BACKGROUND: Myocardial contractility, a significant determinant of cardiac function, is valuable for diagnosis and evaluation of treatment in cardiovascular disorders including heart failure. Shear wave elasticity imaging (SWEI) is a newly developed ultrasound-based elastographic technique that can directly assess the stiffness of cardiac tissue. The aim of this study was to verify the ability of this technique to quantify contractility changes in the myocardium. METHODS: In 12 isolated rabbit hearts, SWEI measurements were made of systolic stiffness at five different coronary perfusion pressures from 0 to 92 mm Hg. The changes in coronary perfusion were used to induce acute stepwise reversible changes in cardiac contractility via the Gregg effect. The Gregg effect is the dependency of contractility on coronary perfusion. In four of the hearts, the measurements were repeated after delivery of gadolinium, which is known to block the Gregg effect. RESULTS: Systolic stiffness measured by SWEI changed linearly with coronary perfusion pressure, with a slope of 0.27 kPa/mm Hg (mean of 95% CI, R2 = 0.73). As expected, the change in contractility due to the Gregg effect was blocked by gadolinium, with a significant reduction of the slope to 0.08 kPa/mm Hg. CONCLUSIONS: SWEI measurements of systolic stiffness provide an index of contractility in the unloaded isolated rabbit heart. Although this study was done under ideal imaging conditions and with nonphysiologic loading conditions, it reinforces the concept that this ultrasound technique has the potential to provide a direct and noninvasive index of cardiac contractility.

A Comparison of Acoustic Radiation Force-Derived Indices of Cardiac Function in the Langendorff Perfused Rabbit Heart.

In the past decade, there has been an increased interest in characterizing cardiac tissue mechanics utilizing newly developed ultrasound-based elastography techniques. These methods excite the tissue mechanically and track the response. Two frequently used methods, acoustic radiation force impulse (ARFI) and shear-wave elasticity imaging (SWEI), have been considered qualitative and quantitative techniques providing relative and absolute measures of tissue stiffness, respectively. Depending on imaging conditions, it is desirable to identify indices of cardiac function that could be measured by ARFI and SWEI and to characterize the relationship between the measures. In this study, we have compared two indices (i.e., relaxation time constant used for diastolic dysfunction assessment and systolic/diastolic stiffness ratio) measured nearly simultaneously by M-mode ARFI and SWEI techniques. We additionally correlated ARFI-measured inverse displacements with SWEI-measured values of the shear modulus of stiffness. For the eight animals studied, the average relaxation time constant ( τ) measured by ARFI and SWEI were ([Formula: see text]) and ([Formula: see text]), respectively ([Formula: see text]). Average systolic/diastolic stiffness ratios for ARFI and SWEI measurements were 6.01±1.37 and 7.12±3.24, respectively ([Formula: see text]). Shear modulus of stiffness (SWEI) was linearly related to inverse displacement values (ARFI) with a 95% CI for the slope of 0.010-0.011 [Formula: see text] ( R(2)=0.73). In conclusion, the relaxation time constant and the systolic/diastolic stiffness ratio were calculated with good agreement between the ARFI- and SWEI-derived measurements. ARFI relative and SWEI absolute stiffness measurements were linearly related with varying slopes based on imaging conditions and subject tissue properties.

The Evolution of Tissue Stiffness at Radiofrequency Ablation Sites During Lesion Formation and in the Peri-Ablation Period.

INTRODUCTION: Elastography imaging can provide radiofrequency ablation (RFA) lesion assessment due to tissue stiffening at the ablation site. An important aspect of assessment is the spatial and temporal stability of the region of stiffness increase in the peri-ablation period. The aim of this study was to use 2 ultrasound-based elastography techniques, shear wave elasticity imaging (SWEI) and acoustic radiation force impulse (ARFI) imaging, to monitor the evolution of tissue stiffness at ablation sites in the 30 minutes following lesion creation. METHODS AND RESULTS: In 6 canine subjects, SWEI measurements and 2-D ARFI images were acquired at 6 ventricular endocardial RFA sites before, during, and for 30 minutes postablation. An immediate increase in tissue stiffness was detected during RFA, and the area of the postablation region of stiffness increase (RoSI) as well as the relative stiffness at the RoSI center was stable approximately 2 minutes after ablation. Of note is the observation that relative stiffness in the region adjacent to the RoSI increased slightly during the first 15 minutes, consistent with local fluid displacement or edema. The magnitude of this increase, ∼0.5-fold from baseline, was significantly less than the magnitude of the stiffness increase directly inside the RoSI, which was greater than 3-fold from baseline. CONCLUSIONS: Ultrasound-based SWEI and ARFI imaging detected an immediate increase in tissue stiffness during RFA, and the stability and magnitude of the stiffness change suggest that consistent elasticity-based lesion assessment is possible 2 minutes after and for at least 30 minutes following ablation.

Ultrasound shear wave elasticity imaging quantifies coronary perfusion pressure effect on cardiac compliance.

Diastolic heart failure (DHF) is a major source of cardiac related morbidity and mortality in the world today. A major contributor to, or indicator of DHF is a change in cardiac compliance. Currently, there is no accepted clinical method to evaluate the compliance of cardiac tissue in diastolic dysfunction. Shear wave elasticity imaging (SWEI) is a novel ultrasound-based elastography technique that provides a measure of tissue stiffness. Coronary perfusion pressure affects cardiac stiffness during diastole; we sought to characterize the relationship between these two parameters using the SWEI technique. In this work, we demonstrate how changes in coronary perfusion pressure are reflected in a local SWEI measurement of stiffness during diastole. Eight Langendorff perfused isolated rabbit hearts were used in this study. Coronary perfusion pressure was changed in a randomized order (0-90 mmHg range) and SWEI measurements were recorded during diastole with each change. Coronary perfusion pressure and the SWEI measurement of stiffness had a positive linear correlation with the 95% confidence interval (CI) for the slope of 0.009-0.011 m/s/mmHg ( R(2) = 0.88 ). Furthermore, shear modulus was linearly correlated to the coronary perfusion pressure with the 95% CI of this slope of 0.035-0.042 kPa/mmHg ( R(2) = 0.83). In conclusion, diastolic SWEI measurements of stiffness can be used to characterize factors affecting cardiac compliance specifically the mechanical interaction (cross-talk) between perfusion pressure in the coronary vasculature and cardiac muscle. This relationship was found to be linear over the range of pressures tested.

Feasibility of near real-time lesion assessment during radiofrequency catheter ablation in humans using acoustic radiation force impulse imaging.

BACKGROUND: Visual confirmation of radiofrequency ablation (RFA) lesions during clinical cardiac ablation procedures could improve procedure efficacy, safety, and efficiency. It was previously shown that acoustic radiation force impulse (ARFI) imaging can identify RFA lesions in vitro and in vivo in an animal model. This is the "first-in-human" feasibility demonstration of intracardiac ARFI imaging of RFA lesions in patients undergoing catheter ablation for atrial flutter (AFL) or atrial fibrillation (AF). METHODS AND RESULTS: Patients scheduled for right atrial (RA) ablation for AFL or left atrial (LA) ablation for drug refractory AF were eligible for imaging. Diastole-gated intracardiac ARFI images were acquired using one of two equipment configurations: (1) a Siemens ACUSON S2000™ ultrasound scanner and 8/10Fr AcuNav™ ultrasound catheter, or (2) a CARTO 3™ integrated Siemens SC2000™ and 10Fr SoundStar™ ultrasound catheter. A total of 11 patients (AFL = 3; AF = 8) were imaged. ARFI images were acquired of ablation target regions, including the RA cavotricuspid isthmus (CTI), and the LA roof, pulmonary vein ostia, posterior wall, posterior mitral valve annulus, and the ridge between the pulmonary vein and LA appendage. ARFI images revealed increased relative myocardial stiffness at ablation catheter contact sites after RFA and at anatomical mapping-tagged RFA treatment sites. CONCLUSIONS: ARFI images from a pilot group of patients undergoing catheter ablation for AFL and AF demonstrate the ability of this technique to identify intra-procedure RFA lesion formation. The results encourage further refinement of ARFI imaging clinical tools and continued investigation in larger clinical trials.

Double Ring Array Catheter for In Vivo Real-Time 3D Ultrasound.

We developed new forward-viewing matrix transducers consisting of double ring arrays of 118 total PZT elements integrated into catheters used to deploy medical interventional devices. Our goal is 3D ultrasound guidance of medical device implantation to reduce x-ray fluoroscopy exposure. The double ring arrays were fabricated on inner and outer custom polyimide flexible circuits with inter-element spacing of 0.20 mm and then wrapped around an 11 French (Fr) catheter to produce a 15 Fr catheter (outer diameter [O.D.]). We used a braided cabling technology to connect the elements to the Volumetrics Medical Imaging (VMI) real-time 3D ultrasound scanner. Transducer performance yielded an average -6 dB fractional bandwidth of 49% ± 11% centered at 4.4 MHz for 118 elements. Real-time 3D cardiac scans of the in vivo pig model yielded good image quality including en face views of the tricuspid valve and real-time 3D guidance of an endo-myocardial biopsy catheter introduced into the left ventricle.

The feasibility of myocardial infarct visualization using atrial kick induced strain (AKIS) contrast.

The most common mechanical measure of the heart integrates ventricular strain between end-diastole and end-systole in order to provide a measure of contraction. Here an approach is described for estimating a correlate to local passive mechanical properties. Passive strain is measured by estimating ventricular strain during atrial systole. During atrial systole the atria contract causing passive stretching in the ventricles from increased volume. This modification to traditional cardiac strain is here termed atrial kick induced strain (AKIS) imaging. AKIS imaging was evaluated in a canine ablation model of chronic infarct and a canine true chronic infarct model. AKIS images of ablation lesions were compared against acoustic radiation force impulse (ARFI) images and tissue blanching, and true chronic infarct AKIS images were compared against delayed enhanced-contrast magnetic resonance. AKIS images were made with 2-D and 3-D ultrasound data. In both studies, AKIS images and the comparison images show good qualitative agreement and good contrast and contrast-to-noise ratio.

Contrast in intracardiac acoustic radiation force impulse images of radiofrequency ablation lesions.

We have previously shown that intracardiac acoustic radiation force impulse (ARFI) imaging visualizes tissue stiffness changes caused by radiofrequency ablation (RFA). The objectives of this in vivo study were to (1) quantify measured ARFI-induced displacements in RFA lesion and unablated myocardium and (2) calculate the lesion contrast (C) and contrast-to-noise ratio (CNR) in two-dimensional ARFI and conventional intracardiac echo images. In eight canine subjects, an ARFI imaging-electroanatomical mapping system was used to map right atrial ablation lesion sites and guide the acquisition of ARFI images at these sites before and after ablation. Readers of the ARFI images identified lesion sites with high sensitivity (90.2%) and specificity (94.3%) and the average measured ARFI-induced displacements were higher at unablated sites (11.23 ± 1.71 µm) than at ablated sites (6.06 ± 0.94 µm). The average lesion C (0.29 ± 0.33) and CNR (1.83 ± 1.75) were significantly higher for ARFI images than for spatially registered conventional B-mode images (C = -0.03 ± 0.28, CNR = 0.74 ± 0.68).

The effect of acute coronary perfusion change on cardiac function measured by Shear Wave Elasticity Imaging.

The possibility of measuring cardiac function noninvasively has generated wide interest in elastography imaging techniques. Shear Wave Elasticity Imaging (SWEI) is an ultrasound-based elastography technique used to measure stiffness of tissues. While this technique has been studied extensively in static homogenous tissues such as liver, breast or prostate, there is still a significant need to study its capabilities to measure cardiac stiffness and function. In this research, we have studied the potential of SWEI to evaluate the coronary perfusion pressure effect on systolic and diastolic stiffness referred to as elastance and compliance of the heart. Five isolated rabbit hearts were used in this study in a Langendorff preparation. SWEI measurements of stiffness were recorded in two steps. In the first step, coronary perfusion was set to normal and then was reduced to half-normal. After 40 minutes of half-normal perfusion, it was returned to normal perfusion for the second step. SWEI velocity decreased from 6.003 m/s to 4.713 m/s in systole and from 1.948 m/s to 1.507 m/s in diastole in the first step. During the second step raising the perfusion to normal, SWEI stiffness showed an increase from 3.760 m/s to 5.468 m/s in systole and from 1.678 m/s to 2.156 m/s during diastole. Our results show that SWEI measurements of stiffness can characterize the cross talk between coronary perfusion and cardiac stiffness and also has the potential to measure compliance and elastance of the heart in systole and diastole.

Acoustic radiation force impulse imaging of mechanical stiffness propagation in myocardial tissue.

Acoustic radiation force impulse (ARFI) imaging has been shown to be capable of imaging local myocardial stiffness changes throughout the cardiac cycle. Expanding on these results, the authors present experiments using cardiac ARFI imaging to visualize and quantify the propagation of mechanical stiffness during ventricular systole. In vivo ARFI images of the left ventricular free wall of two exposed canine hearts were acquired. Images were formed while the heart was externally paced by one of two electrodes positioned on the epicardial surface and either side of the imaging plane. Two-line M-mode ARFI images were acquired at a sampling frequency of 120 Hz while the heart was paced from an external stimulating electrode. Two-dimensional ARFI images were also acquired, and an average propagation velocity across the lateral field of view was calculated. Directions and speeds of myocardial stiffness propagation were measured and compared with the propagations derived from the local electrocardiogram (ECG), strain, and tissue velocity measurements estimated during systole. In all ARFI images, the direction of myocardial stiffness propagation was seen to be away from the stimulating electrode and occurred with similar velocity magnitudes in either direction. When compared with the local epicardial ECG, the mechanical stiffness waves were observed to travel in the same direction as the propagating electrical wave and with similar propagation velocities. In a comparison between ARFI, strain, and tissue velocity imaging, the three methods also yielded similar propagation velocities.

Intracardiac acoustic radiation force impulse imaging: a novel imaging method for intraprocedural evaluation of radiofrequency ablation lesions.

BACKGROUND: Arrhythmia recurrence after cardiac radiofrequency ablation (RFA) for atrial fibrillation has been linked to conduction through discontinuous lesion lines. Intraprocedural visualization and corrective ablation of lesion line discontinuities could decrease postprocedure atrial fibrillation recurrence. Intracardiac acoustic radiation force impulse (ARFI) imaging is a new imaging technique that visualizes RFA lesions by mapping the relative elasticity contrast between compliant-unablated and stiff RFA-treated myocardium. OBJECTIVE: To determine whether intraprocedure ARFI images can identify RFA-treated myocardium in vivo. METHODS: In 8 canines, an electroanatomical mapping-guided intracardiac echo catheter was used to acquire 2-dimensional ARFI images along right atrial ablation lines before and after RFA. ARFI images were acquired during diastole with the myocardium positioned at the ARFI focus (1.5 cm) and parallel to the intracardiac echo transducer for maximal and uniform energy delivery to the tissue. Three reviewers categorized each ARFI image as depicting no lesion, noncontiguous lesion, or contiguous lesion. For comparison, 3 separate reviewers confirmed RFA lesion presence and contiguity on the basis of functional conduction block at the imaging plane location on electroanatomical activation maps. RESULTS: Ten percent of ARFI images were discarded because of motion artifacts. Reviewers of the ARFI images detected RFA-treated sites with high sensitivity (95.7%) and specificity (91.5%). Reviewer identification of contiguous lesions had 75.3% specificity and 47.1% sensitivity. CONCLUSIONS: Intracardiac ARFI imaging was successful in identifying endocardial RFA treatment when specific imaging conditions were maintained. Further advances in ARFI imaging technology would facilitate a wider range of imaging opportunities for clinical lesion evaluation.

Intracardiac echocardiography measurement of dynamic myocardial stiffness with shear wave velocimetry.

Acoustic radiation force (ARF)-based methods have been demonstrated to be a viable tool for noninvasively estimating tissue elastic properties, and shear wave velocimetry has been used to measure quantitatively the stiffening and relaxation of myocardial tissue in open-chest experiments. Dynamic stiffness metrics may prove to be indicators for certain cardiac diseases, but a clinically viable means of remotely generating and tracking transverse wave propagation in myocardium is needed. Intracardiac echocardiography (ICE) catheter-tip transducers are demonstrated here as a viable tool for making this measurement. ICE probes achieve favorable proximity to the myocardium, enabling the use of shear wave velocimetry from within the right ventricle throughout the cardiac cycle. This article describes the techniques used to overcome the challenges of using a small probe to perform ARF-driven shear-wave velocimetry and presents in vivo porcine data showing the effectiveness of this method in the interventricular septum.

Dual-mode IVUS transducer for image-guided brain therapy: preliminary experiments.

In this study, we investigated the feasibility of using 3.5-Fr intravascular ultrasound (IVUS) catheters for minimally-invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated by: (1) retro-fitting a commercial 3.5-Fr IVUS catheter with a 5 × 0.5 × 0.22 mm PZT-4 transducer for 9-MHz imaging and (2) testing an identical transducer for therapy potential with 3.3-MHz continuous-wave excitation. The imaging transducer was compared with a 9-Fr, 9-MHz ICE catheter when visualizing the post-mortem ovine brain and was also used to attempt vascular access to an in vivo porcine brain. A net average electrical power input of 700 mW was applied to the therapy transducer, producing a temperature rise of +13.5°C at a depth of 1.5 mm in live brain tumor tissue in the mouse model. These results suggest that it may be feasible to combine the imaging and therapeutic capabilities into a single device as a clinically-viable instrument.

Excitation properties of the right cervical vagus nerve in adult dogs.

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression, and it is currently under investigation for applications in Alzheimer's disease, anxiety, heart failure, and obesity. However, the mechanism(s) by which VNS has its effects are not clear, and the stimulation parameters for obtaining therapeutic outcomes appear highly variable. The purpose of this study was to quantify the excitation properties of the right cervical vagus nerve in adult dogs anesthetized with propofol and fentanyl. Input-output curves of the right cervical vagus nerve compound action potential and laryngeal muscle electromyogram were measured in response to VNS across a range of stimulation parameters: amplitudes of 0.02-50mA, pulsewidths of 10, 50, 100, 200, 300, 500, and 1,000µs, frequencies of 1-2Hz, and train lengths of 20 pulses with 3 different electrode configurations: monopolar cathode, proximal anode/distal cathode, and proximal cathode/distal anode. Electrode configuration and stimulation waveform (monophasic vs. asymmetric charge-balanced biphasic) did not affect the threshold or recruitment of the vagal nerve fibers that were activated. The rheobase currents of A- and B-fibers were 0.4mA and 0.7mA, respectively, and the chronaxie of both components was 180µs. Pulsewidth had little effect on the normalized threshold difference between activation of A- and B-fibers. The results provide insight into the complement of nerve fibers activated by VNS and guidance to clinicians for the selection of optimal stimulation parameters.

Selective control of physiological responses by temporally-patterned electrical stimulation of the canine vagus nerve.

Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 µs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy.

An in vitro assessment of acoustic radiation force impulse imaging for visualizing cardiac radiofrequency ablation lesions.

INTRODUCTION: Lesion placement and transmurality are critical factors in the success of cardiac transcatheter radiofrequency ablation (RFA) treatments for supraventricular arrhythmias. This study investigated the capabilities of catheter transducer based acoustic radiation force impulse (ARFI) ultrasound imaging for quantifying ablation lesion dimensions. METHODS AND RESULTS: RFA lesions were created in vitro in porcine ventricular myocardium and imaged with an intracardiac ultrasound catheter transducer capable of acquiring spatially registered B-mode and ARFI images. The myocardium was sliced along the imaging plane and photographed. The maximum ARFI-induced displacement images of the lesion were normalized and spatially registered with the photograph by matching the surfaces of the tissue in the B-mode and photographic images. The lesion dimensions determined by a manual segmentation of the photographed lesion based on the visible discoloration of the tissue were compared to automatic segmentations of the ARFI image using 2 different calculated thresholds. ARFI imaging accurately localized and sized the lesions within the myocardium. Differences in the maximum lateral and axial dimensions were statistically below 2 mm and 1 mm, respectively, for the 2 thresholding methods, with mean percent overlap of 68.7 +/- 5.21% and 66.3 +/- 8.4% for the 2 thresholds used. CONCLUSION: ARFI imaging is capable of visualizing myocardial RFA lesion dimensions to within 2 mm in vitro. Visualizing lesions during transcatheter cardiac ablation procedures could improve the success of the treatment by imaging lesion line discontinuity and potentially reducing the required number of ablation lesions and procedure time.