Determining value of Coordinated Registry Networks (CRNs): a case of transcatheter valve therapies.

BACKGROUND: The Transcatheter Valve Therapy (TVT) Coordinated Registry Network (CRN) supported 23 regulatory decisions and ensured evidence-based evaluation of the application of TVT technology. However, there are cost concerns that require value assessment of the TVT CRN compared with traditional study designs. OBJECTIVES: We aimed to determine the value created by the TVT CRN based on (1) Return on investment (ROI), (2) Time saved (TS) in conducting necessary regulatory studies. METHODS: For both ROI and TS analyses, we compared studies that used the TVT CRN with those that would have been required if the registry did not exist (counterfactual studies). To estimate ROI, we accounted for the costs of investment and gain from investment. Both the counterfactual costs and length of studies were projected using design specifications determined by US Food and Drug Administration (FDA) reviewers. RESULTS: We identified 21 studies using the TVT CRN (supporting 23 FDA decisions) that generated evidence on TVT for three device manufacturers. ROI is estimated to be greater than 550%. TS by using the CRN ranged from months to years. CONCLUSIONS: The CRN method to evidence generation creates value for manufacturers and the broader device ecosystem, demonstrated with this example of the TVT CRN. The public health benefits of evidence created by this CRN outweighs the difference in data quality between traditional clinical studies and the CRN method.

Improving Displacement Signal-to-Noise Ratio for Low-Signal Radiation Force Elasticity Imaging Using Bayesian Techniques.

Radiation force-based elasticity imaging is currently being investigated as a possible diagnostic modality for a number of clinical tasks, including liver fibrosis staging and the characterization of cardiovascular tissue. In this study, we evaluate the relationship between peak displacement magnitude and image quality and propose using a Bayesian estimator to overcome the challenge of obtaining viable data in low displacement signal environments. Displacement data quality were quantified for two common radiation force-based applications, acoustic radiation force impulse imaging, which measures the displacement within the region of excitation, and shear wave elasticity imaging, which measures displacements outside the region of excitation. Performance as a function of peak displacement magnitude for acoustic radiation force impulse imaging was assessed in simulations and lesion phantoms by quantifying signal-to-noise ratio (SNR) and contrast-to-noise ratio for varying peak displacement magnitudes. Overall performance for shear wave elasticity imaging was assessed in ex vivo chicken breast samples by measuring the displacement SNR as a function of distance from the excitation source. The results show that for any given displacement magnitude level, the Bayesian estimator can increase the SNR by approximately 9 dB over normalized cross-correlation and the contrast-to-noise ratio by a factor of two. We conclude from the results that a Bayesian estimator may be useful for increasing data quality in SNR-limited imaging environments.

Robust Tracking of Small Displacements With a Bayesian Estimator.

Radiation-force-based elasticity imaging describes a group of techniques that use acoustic radiation force (ARF) to displace tissue to obtain qualitative or quantitative measurements of tissue properties. Because ARF-induced displacements are on the order of micrometers, tracking these displacements in vivo can be challenging. Previously, it has been shown that Bayesian-based estimation can overcome some of the limitations of a traditional displacement estimator such as normalized cross-correlation (NCC). In this work, we describe a Bayesian framework that combines a generalized Gaussian-Markov random field (GGMRF) prior with an automated method for selecting the prior's width. We then evaluate its performance in the context of tracking the micrometer-order displacements encountered in an ARF-based method such as ARF impulse (ARFI) imaging. The results show that bias, variance, and mean-square error (MSE) performance vary with prior shape and width, and that an almost one order-of-magnitude reduction in MSE can be achieved by the estimator at the automatically selected prior width. Lesion simulations show that the proposed estimator has a higher contrast-to-noise ratio but lower contrast than NCC, median-filtered NCC, and the previous Bayesian estimator, with a non-Gaussian prior shape having better lesion-edge resolution than a Gaussian prior. In vivo results from a cardiac, radio-frequency ablation ARFI imaging dataset show quantitative improvements in lesion contrast-to-noise ratio over NCC as well as the previous Bayesian estimator.

Quantitative Imaging Assessment of an Alternative Approach to Surgical Mitral Valve Leaflet Resection: An Acute Porcine Study.

This study reports the initial in vivo use of a combined radiofrequency ablation and cryo-anchoring (RFC) catheter as an alternative to surgical mitral valve (MV) leaflet resection. Radiofrequency ablation thermally shrinks enlarged collagenous tissues, providing an alternative to leaflet resection, and cryo-anchoring provides reversible attachment of a catheter to freely mobile MV leaflets. Excised porcine MVs (n = 9) were tested in a left heart flow simulator to establish treatment efficacy criteria. Resected leaflet area was quantified by tracking markers on the leaflet surface, and leaflet length reductions were directly measured on echocardiography. Leaflet area decreased by 38 ± 2.7%, and leaflet length decreased by 9.2 ± 1.8% following RFC catheter treatment. The RFC catheter was then tested acutely in healthy pigs (n = 5) under epicardial echocardiographic guidance, open-chest without cardiopulmonary bypass, using mid-ventricular free wall access. Leaflet length was quantified using echocardiography. Quantitative assessment of MV leaflet length revealed that leaflet resection was successful in 4 of 5 pigs, with a leaflet length reduction of 13.3 ± 4.6%. Histological, mechanical, and gross pathological findings also confirmed that RFC catheter treatment was efficacious. The RFC catheter significantly reduces MV leaflet size in an acute animal model, providing a possible percutaneous alternative to surgical leaflet resection.

A model and regularization scheme for ultrasonic beamforming clutter reduction.

Acoustic clutter produced by off-axis and multipath scattering is known to cause image degradation, and in some cases these sources may be the prime determinants of in vivo image quality. We have previously shown some success addressing these sources of image degradation by modeling the aperture domain signal from different sources of clutter, and then decomposing aperture domain data using the modeled sources. Our previous model had some shortcomings including model mismatch and failure to recover B-Mode speckle statistics. These shortcomings are addressed here by developing a better model and by using a general regularization approach appropriate for the model and data. We present results with L1 (lasso), L2 (ridge), and L1/L2 combined (elastic-net) regularization methods. We call our new method aperture domain model image reconstruction (ADMIRE). Our results demonstrate that ADMIRE with L1 regularization, or weighted toward L1 in the case of elastic-net regularization, have improved image quality. L1 by itself works well, but additional improvements are seen with elastic-net regularization over the pure L1 constraint. On in vivo example cases, L1 regularization showed mean contrast improvements of 4.6 and 6.8 dB on fundamental and harmonic images, respectively. Elastic net regularization (α = 0.9) showed mean contrast improvements of 17.8 dB on fundamental images and 11.8 dB on harmonic images. We also demonstrate that in uncluttered Field II simulations the decluttering algorithm produces the same contrast, contrast-tonoise ratio, and speckle SNR as normal B-mode imaging, demonstrating that ADMIRE preserves typical image features.

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.

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).

Acoustic radiation force impulse imaging of vulnerable plaques: a finite element method parametric analysis.

Plaque rupture is the most common cause of complications such as stroke and coronary heart failure. Recent histopathological evidence suggests that several plaque features, including a large lipid core and a thin fibrous cap, are associated with plaques most at risk for rupture. Acoustic Radiation Force Impulse (ARFI) imaging, a recently developed ultrasound-based elasticity imaging technique, shows promise for imaging these features noninvasively. Clinically, this could be used to distinguish vulnerable plaques, for which surgical intervention may be required, from those less prone to rupture. In this study, a parametric analysis using Finite Element Method (FEM) models was performed to simulate ARFI imaging of five different carotid artery plaques across a wide range of material properties. It was demonstrated that ARFI imaging could resolve the softer lipid pool from the surrounding, stiffer media and fibrous cap and was most dependent upon the stiffness of the lipid pool component. Stress concentrations due to an ARFI excitation were located in the media and fibrous cap components. In all cases, the maximum Von Mises stress was<1.2 kPa. In comparing these results with others investigating plaque rupture, it is concluded that while the mechanisms may be different, the Von Mises stresses imposed by ARFI imaging are orders of magnitude lower than the stresses associated with blood pressure.

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.

Noninvasive assessment of wall-shear rate and vascular elasticity using combined ARFI/SWEI/spectral Doppler imaging system.

The progression of atherosclerotic disease is a complex process believed to be a function of the localized mechanical properties and hemodynamic loading associated with the arterial wall. It is hypothesized that measurements of cardiovascular stiffness and wall-shear rate (WSR) may provide important information regarding vascular remodeling, endothelial function and the growth of soft lipid-filled plaques that could help a clinician better predict the occurrence of clinical events such as stroke. Two novel ARFI based imaging techniques, combined on-axis/off-axis ARFI/Spectral Doppler Imaging (SAD-SWEI) and Gated 2D ARFI/Spectral Doppler Imaging (SAD-Gated), were developed to form co-registered depictions of B-mode echogenicity, ARFI displacements, ARF-excited transverse wave velocity estimates and estimates ofwall-shear rate throughout the cardiac cycle. Implemented on a commercial ultrasound scanner, the developed techniques were evaluated in tissue-mimicking and steady-state flow phantoms and compared with conventional techniques, other published study results and theoretical values. Initial in vivo feasibility of the method is demonstrated with results obtained from scanning the carotid arteries of five healthy volunteers. Cyclic variations over the cardiac cycle were observed in on-axis displacements, off-axis transverse-wave velocities and wall-shear rates.

Comparison of physiological motion filters for in vivo cardiac ARFI.

Acoustic radiation force impulse (ARFI) imaging is being utilized to investigate mechanical properties ofcardiac tissue. The underlying physiological motion, however, presents a major challenge. This paper aims to investigate the effectiveness of various physiological motion filters using in vivo canine data with a simulated ARFI push pulse. Ideally, the motion filter will exactly model the physiological motion and, when subtracted from the total displacement, leave only the simulated ARFI displacement profile. We investigated three temporal quadratic motion filters: (1)interpolation, (2) extrapolation and (3) a weighted technique. Additionally, the various motion filters were compared when using 1-D versus 2-D autocorrelation methods to estimate motion. It was found that 2D-autocorrelation always produced better physiological motion estimates regardless of the type of filter used. The extrapolation filter gives the most accurate estimate of the physiological motion at times immediately after the ARFI push (0.1 ms) while a close-time interpolation filter using displacement estimates at times before full tissue recovery gives the most accurate estimates at later times after the ARFI push (0.7 ms). While improvements to the motion filter during atrial systole and the onset of ventricular systole are needed, the weighted, close-time interpolation and extrapolation motion filters all offer promising results for estimating cardiac physiological motion more accurately, while allowing faster ARFI frame rates than previous motion filters. This study demonstrates the ability to eliminate physiological motion in a clinically-feasible manner, opening the door for more extensive clinical experimentation.

The development and potential of acoustic radiation force impulse (ARFI) imaging for carotid artery plaque characterization.

Stroke is the third leading cause of death and long-term disability in the USA. Currently, surgical intervention decisions in asymptomatic patients are based upon the degree of carotid artery stenosis. While there is a clear benefit of endarterectomy for patients with severe (> 70%) stenosis, in those with high/moderate (50-69%) stenosis the evidence is less clear. Evidence suggests ischemic stroke is associated less with calcified and fibrous plaques than with those containing softer tissue, especially when accompanied by a thin fibrous cap. A reliable mechanism for the identification of individuals with atherosclerotic plaques which confer the highest risk for stroke is fundamental to the selection of patients for vascular interventions. Acoustic radiation force impulse (ARFI) imaging is a new ultrasonic-based imaging method that characterizes the mechanical properties of tissue by measuring displacement resulting from the application of acoustic radiation force. These displacements provide information about the local stiffness of tissue and can differentiate between soft and hard areas. Because arterial walls, soft tissue, atheromas, and calcifications have a wide range in their stiffness properties, they represent excellent candidates for ARFI imaging. We present information from early phantom experiments and excised human limb studies to in vivo carotid artery scans and provide evidence for the ability of ARFI to provide high-quality images which highlight mechanical differences in tissue stiffness not readily apparent in matched B-mode images. This allows ARFI to identify soft from hard plaques and differentiate characteristics associated with plaque vulnerability or stability.

Acoustic radiation force impulse imaging on ex vivo abdominal aortic aneurysm model.

A method for reliable, noninvasive estimation of abdominal aortic aneurysms (AAA) wall mechanics may be a useful clinical tool for rupture prediction. An in vitro AAA model was developed from an excised porcine aorta with elastase treatment. The AAA model behaviour was analysed using acoustic radiation force impulse (ARFI) imaging techniques to generate and measure wave propagation in both aneurysmal and normal aortic tissue. Opening angle measurement showed a fourfold decrease from healthy aorta to AAA model and pathologic analysis verified this elastin degradation. Maximum wave velocity at 180 mm Hg was 7 mm/ms for healthy tissue and 8.26 mm/ms for the aneurysmal tissue. The mechanical changes produced in the artificially induced aneurysm were found to be detectable using ARFI imaging.

Novel acoustic radiation force impulse imaging methods for visualization of rapidly moving tissue.

Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing changes in local myocardial stiffness through a normal cardiac cycle. As a beating heart involves rapidly-moving tissue with cyclically-varying myocardial stiffness, it is desirable to form images with high frame rates and minimize susceptibility to motion artifacts. Three novel ARFI imaging methods, pre-excitation displacement estimation, parallel-transmit excitation and parallel-transmit tracking, were implemented. Along with parallel-receive, ECG-gating and multiplexed imaging, these new techniques were used to form high-quality, high-resolution epicardial ARFI images. Three-line M-mode, extended ECG-gated three-line M-mode and ECG-gated two-dimensional ARFI imaging sequences were developed to address specific challenges related to cardiac imaging. In vivo epicardial ARFI images of an ovine heart were formed using these sequences and the quality and utility of the resultant ARFI-induced displacement curves were evaluated. The ARFI-induced displacement curves demonstrate the potential for ARFI imaging to provide new and unique information into myocardial stiffness with high temporal and spatial resolution.

Lower-limb vascular imaging with acoustic radiation force elastography: demonstration of in vivo feasibility.

Acoustic radiation force impulse (ARFI) imaging characterizes the mechanical properties of tissue by measuring displacement resulting from applied ultrasonic radiation force. In this paper, we describe the current status of ARFI imaging for lower-limb vascular applications and present results from both tissue-mimicking phantoms and in vivo experiments. Initial experiments were performed on vascular phantoms constructed with polyvinyl alcohol for basic evaluation of the modality. Multilayer vessels and vessels with compliant occlusions of varying plaque load were evaluated with ARFI imaging techniques. Phantom layers and plaque are well resolved in the ARFI images, with higher contrast than B-mode, demonstrating the ability of ARFI imaging to identify regions of different mechanical properties. Healthy human subjects and those with diagnosed lower-limb peripheral arterial disease were imaged. Proximal and distal vascular walls are well visualized in ARFI images, with higher mean contrast than corresponding B-mode images. ARFI images reveal information not observed by conventional ultrasound and lend confidence to the feasibility of using ARFI imaging during lower-limb vascular workup.

Acoustic radiation force impulse imaging for noninvasive characterization of carotid artery atherosclerotic plaques: a feasibility study.

Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of atherosclerotic plaque to rupture, however, is challenging to determine by any imaging method. In this study, acoustic radiation force impulse (ARFI) imaging is applied to atherosclerotic disease in the carotid artery to determine the feasibility of using ARFI to noninvasively characterize carotid plaques. ARFI imaging is a useful method for characterizing the local mechanical properties of tissue and is complementary to B-mode imaging. ARFI imaging can readily distinguish between stiff and soft regions of tissue. High-resolution images of both homogeneous and heterogeneous plaques were observed. Homogeneous plaques were indistinguishable in stiffness from vascular tissue. However, they showed thicknesses much greater than normal vascular tissue. In heterogeneous plaques, large and small soft regions were observed, with the smallest observed soft region having a diameter of 0.5 mm. A stiff cap was observed covering the large soft tissue region, with the cap thickness ranging from 0.7-1.3 mm.

In vivo guidance and assessment of liver radio-frequency ablation with acoustic radiation force elastography.

The initial results from clinical trials investigating the utility of acoustic radiation force impulse (ARFI) imaging for use with radio-frequency ablation (RFA) procedures in the liver are presented. To date, data have been collected from 6 RFA procedures in 5 unique patients. Large displacement contrast was observed in ARFI images of both pre-ablation malignancies (mean 7.5 dB, range 5.7-11.9 dB) and post-ablation thermal lesions (mean 6.2 dB, range 5.1-7.5 dB). In general, ARFI images provided superior boundary definition of structures relative to the use of conventional sonography alone. Although further investigations are required, initial results are encouraging and demonstrate the clinical promise of the ARFI method for use in many stages of RFA procedures.

In vivo assessment of myocardial stiffness with acoustic radiation force impulse imaging.

Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing variations in local stiffness within soft tissue. Recent advances in ARFI beam sequencing and parallel imaging have shortened acquisition times and lessened transducer heating to a point where ARFI acquisitions can be executed at high frame rates on commercially available diagnostic scanners. In vivo ARFI images were acquired with a linear array placed on an exposed canine heart. The electrocardiogram (ECG) was also recorded. When coregistered with the ECG, ARFI displacement images of the heart reflect the expected myocardial stiffness changes during the cardiac cycle. A radio-frequency ablation was performed on the epicardial surface of the left ventricular free wall, creating a small lesion that did not vary in stiffness during a heartbeat, though continued to move with the rest of the heart. ARFI images showed a hemispherical, stiffer region at the ablation site whose displacement magnitude and temporal variation through the cardiac cycle were less than the surrounding untreated myocardium. Sequences with radiation force pulse amplitudes set to zero were acquired to measure potential cardiac motion artifacts within the ARFI images. The results show promise for real-time cardiac ARFI imaging.