Preliminary Feasibility of Stress Myocardial Elastography for the Detection of Coronary Artery Disease.

Myocardial elastography (ME) is a cardiac strain imaging technique that has been found capable of detecting a decrease in radial strain caused by ischemia or infarction in patients with coronary artery disease (CAD) as well as in a canine model. Prior studies have focused on rest imaging, but stress testing can reveal functional deficits caused by stenoses that are asymptomatic at rest. Therefore, it has been proposed that stress ME (S-ME) improves the detection of CAD. A novel strain difference (Δε) metric is presented and investigated in a canine model of induced ischemia, as well as in a study in human patients with CAD validated by myocardial perfusion imaging. In the canine model study, flow-limiting stenosis was induced by partial ligation in n = 2 canines, and stenosis was found to consistently reduce Δε in the affected myocardial regions compared with baseline, as well as compared to myocardial regions that are remote to the induced stenosis. In the clinical study, the median Δε was significantly lower (p < 0.05) in infarcted myocardial regions (-6.29%) than in those with normal perfusion (4.62%), with Δε in ischemic regions falling in between (-2.91%). The same trend was observed when considering radial strain during stress and, to a lesser degree, at rest alone. The results indicate that S-ME may be more sensitive to mild cases of CAD that are functionally asymptomatic at rest.

Adaptive Wall Shear Stress Imaging in Phantoms, Simulations and In Vivo.

WSS measurement is challenging since it requires sensitive flow measurements at a distance close to the wall. The aim of this study is to develop an ultrasound imaging technique which combines vector flow imaging with an unsupervised data clustering approach that automatically detects the region close to the wall with optimally linear flow profile, to provide direct and robust WSS estimation. The proposed technique was evaluated in phantoms, mimicking normal and atherosclerotic vessels, and spatially registered Fluid Structure Interaction (FSI) simulations. A relative error of 6.7% and 19.8% was obtained for peak systolic (WSSPS) and end diastolic (WSSED) WSS in the straight phantom, while in the stenotic phantom, a good similarity was found between measured and simulated WSS distribution, with a correlation coefficient, R, of 0.89 and 0.85 for WSSPS and WSSED, respectively. Moreover, the feasibility of the technique to detect pre-clinical atherosclerosis was tested in an atherosclerotic swine model. Six swines were fed atherogenic diet, while their left carotid artery was ligated in order to disturb flow patterns. Ligated arterial segments that were exposed to low WSSPS and WSS characterized by high frequency oscillations at baseline, developed either moderately or highly stenotic plaques (p < 0.05). Finally, feasibility of the technique was demonstrated in normal and atherosclerotic human subjects. Atherosclerotic carotid arteries with low stenosis had lower WSSPS as compared to control subjects (p < 0.01), while in one subject with high stenosis, elevated WSS was found on an arterial segment, which coincided with plaque rupture site, as determined through histological examination.

Myocardial Strain Imaging With Electrocardiogram-Gated and Coherent Compounding for Early Diagnosis of Coronary Artery Disease.

Myocardial elastography (ME) is an ultrasound-based technique that uses radiofrequency signals for 2-D cardiac motion tracking and strain imaging at a high frame rate. Early diagnosis of coronary artery disease (CAD) is critical for timely treatment and improvement of patient outcome. The objective of this study was to assess the performance of ME radial and circumferential strains in the detection and characterization of CAD in patients. In this study, 86 patients suspected of CAD were imaged with ME prior to invasive coronary angiography (ICA). End-systolic radial and circumferential left ventricular strains were estimated in all patients in each of their perfusion territories: left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA). ME radial strains were capable of differentiating the obstructive CAD group (55.3 ± 29.8%) from the non-obstructive CAD (72.5 ± 46.8%, p < 0.05) and no CAD groups (73.4 ± 30.4%, p < 0.05) in the RCA territory. ME circumferential strains were capable of differentiating the obstructive CAD group (-3.1 ± 7.5%) from the non-obstructive CAD (-7.2 ± 6.8%, p < 0.05) and normal (-6.9 ± 8.0%, p < 0.05) groups in the LAD territory and to differentiate the normal group (-17.1 ± 8.2%) from the obstructive (-12.8 ± 7.2%, p < 0.05) and non-obstructive CAD (-13.6 ± 8.5%, p < 0.05) groups in the RCA territory. ME circumferential strain performed better than ME radial strain in differentiating normal, non-obstructive and obstructive perfusion territories. In the LCX territory, both ME radial and circumferential strains decreased when the level of stenosis was higher. However, it was not statistically significant. The findings presented herein indicate that ME radial and circumferential estimation obtained from ECG-gated and compounded acquisitions is a promising tool for early, non-invasive and radiation-free detection of CAD in patients.

Real-Time Passive Acoustic Mapping Using Sparse Matrix Multiplication.

Passive acoustic mapping enables the spatiotemporal monitoring of cavitation with circulating microbubbles during focused ultrasound (FUS)-mediated blood-brain barrier opening. However, the computational load for processing large data sets of cavitation maps or more complex algorithms limit the visualization in real-time for treatment monitoring and adjustment. In this study, we implemented a graphical processing unit (GPU)-accelerated sparse matrix-based beamforming and time exposure acoustics in a neuronavigation-guided ultrasound system for real-time spatiotemporal monitoring of cavitation. The system performance was tested in silico through benchmarking, in vitro using nonhuman primate (NHP) and human skull specimens, and demonstrated in vivo in NHPs. We demonstrated the stability of the cavitation map for integration times longer than 62.5 [Formula: see text]. A compromise between real-time displaying and cavitation map quality obtained from beamformed RF data sets with a size of 2000 ×128 ×30 (axial [Formula: see text]) was achieved for an integration time of [Formula: see text], which required a computational time of 0.27 s (frame rate of 3.7 Hz) and could be displayed in real-time between pulses at PRF = 2 Hz. Our benchmarking tests show that the GPU sparse-matrix algorithm processed the RF data set at a computational rate of [Formula: see text]/pixel/sample, which enables adjusting the frame rate and the integration time as needed. The neuronavigation system with real-time implementation of cavitation mapping facilitated the localization of the cavitation activity and helped to identify distortions due to FUS phase aberration. The in vivo test of the method demonstrated the feasibility of GPU-accelerated sparse matrix computing in a close to a clinical condition, where focus distortions exemplify problems during treatment. These experimental conditions show the need for spatiotemporal monitoring of cavitation with real-time capability that enables the operator to correct or halt the sonication in case substantial aberrations are observed.

A comparison between unfocused and focused transmit strategies in cardiac strain imaging.

Unfocused ultrasound imaging, particularly coherent compounding with diverging waves, is a commonly employed high-frame rate transmit strategy in cardiac strain imaging. However, the accuracy and precision of diverging wave imaging compared to focused-beam transmit approaches in human subjects is unknown. Three transmit strategies-coherent compounding imaging, composite focused imaging with ECG gating and narrow-beams, and focused imaging with wide-beams-were compared in simulation and in transthoracic imaging of healthy human subjects (n = 7). The focused narrow-beam sequence estimated radial end-systolic cumulative strains of a simulated left ventricular deformation with 26% ± 1.5% and 34% ± 1.5% greater accuracy compared with compounding and wide-beam imaging, respectively. Strain estimation precision in transthoracic imaging was then assessed with the Strain Filter on cumulative end-systolic radial strains. Within the strain values where statistically significant differences in precision (E(SNRe|ε)) were found between transmit strategies, the narrow-beam sequence estimated radial strain 13% ± 0.71% and 34% ± 8.9% more precisely on average compared to compounding or wide-beam imaging, respectively.

Catheter Ablation Lesion Visualization With Intracardiac Strain Imaging in Canines and Humans.

Catheter ablation is a common treatment for arrhythmia, but can fail if lesion lines are noncontiguous. Identification of gaps and nontransmural lesions can reduce the likelihood of treatment failure and recurrent arrhythmia. Intracardiac myocardial elastography (IME) is a strain imaging technique that provides visualization of the lesion line. Estimation of lesion size and gap resolution were evaluated in an open-chest canine model ( n = 3 ), and clinical feasibility was investigated in patients undergoing ablation to treat typical cavotricuspid isthmus (CTI) atrial flutter ( n = 5 ). A lesion line consisting of three lesions and two gaps was generated on the canine left ventricle via epicardial ablation. One lesion was generated in one canine right ventricle. Average lesion and gap areas were measured with high agreement (33 ± 14 and 30 ± 15 mm2, respectively) when compared against gross pathology (34 ± 19 and 26 ± 11 mm2, respectively). Gaps as small as 11 mm2 (3.6 mm on epicardial surface) were identifiable. Absolute error and relative error in estimated lesion area were 9.3 ± 8.4 mm2 and 31% ± 34%; error in estimated gap area was 11 ± 9.0 mm2 and 40% ± 29%. Flutter patients were imaged throughout the procedure. Strain was shown to be capable of differentiating between baseline and after ablation completion as confirmed by conduction block. In all patients, strain decreased in the CTI after ablation (mean paired difference of -17% ± 11%, ). IME could potentially become a useful ablation monitoring tool in health facilities.

4D cardiac electromechanical activation imaging.

Cardiac abnormalities, a major cause of morbidity and mortality, affect millions of people worldwide. Despite the urgent clinical need for early diagnosis, there is currently no noninvasive technique that can infer to the electrical function of the whole heart in 3D and thereby localize abnormalities at the point of care. Here we present a new method for noninvasive 4D mapping of the cardiac electromechanical activity in a single heartbeat for heart disease characterization such as arrhythmia and infarction. Our novel technique captures the 3D activation wave of the heart in vivo using high volume-rate (500 volumes per second) ultrasound with a 32 × 32 matrix array. Electromechanical activation maps are first presented in a normal and infarcted cardiac model in silico and in canine heart during pacing and re-entrant ventricular tachycardia in vivo. Noninvasive 4D electromechanical activation mapping in a healthy volunteer and a heart failure patient are also determined. The technique described herein allows for direct, simultaneous and noninvasive visualization of electromechanical activation in 3D, which provides complementary information on myocardial viability and/or abnormality to clinical imaging.

Compressed sensing reconstruction of synthetic transmit aperture dataset for volumetric diverging wave imaging.

A high volume rate and high performance ultrasound imaging method based on a matrix array is proposed by using compressed sensing (CS) to reconstruct the complete dataset of synthetic transmit aperture (STA) from three-dimensional (3D) diverging wave transmissions (i.e. 3D CS-STA). Hereto, a series of apodized 3D diverging waves are transmitted from a fixed virtual source, with the ith row of a Hadamard matrix taken as the apodization coefficients in the ith transmit event. Then CS is used to reconstruct the complete dataset, based on the linear relationship between the backscattered echoes and the complete dataset of 3D STA. Finally, standard STA beamforming is applied on the reconstructed complete dataset to obtain the volumetric image. Four layouts of element numbering for apodizations and transmit numbers of 16, 32 and 64 are investigated through computer simulations and phantom experiments. Furthermore, the proposed 3D CS-STA setups are compared with 3D single-line-transmit (SLT) and 3D diverging wave compounding (DWC). The results show that, (i) 3D CS-STA has competitive lateral resolutions to 3D STA, and their contrast ratios (CRs) and contrast-to-noise ratios (CNRs) approach to those of 3D STA as the number of transmit events increases in noise-free condition. (ii) the tested 3D CS-STA setups show good robustness in complete dataset reconstruction in the presence of different levels of noise. (iii) 3D CS-STA outperforms 3D SLT and 3D DWC. More specifically, the 3D CS-STA setup with 64 transmit events and the Random layout achieves ~31% improvement in lateral resolution, ~14% improvement in ratio of the estimated-to-true cystic areas, a higher volume rate, and competitive CR/CNR when compared with 3D DWC. The results demonstrate that 3D CS-STA has great potential of providing high quality volumetric image with a higher volume rate.

Optimization of Transmit Parameters in Cardiac Strain Imaging With Full and Partial Aperture Coherent Compounding.

Coherent compounding methods using the full or partial transmit aperture have been investigated as a possible means of increasing strain measurement accuracy in cardiac strain imaging; however, the optimal transmit parameters in either compounding approach have yet to be determined. The relationship between strain estimation accuracy and transmit parameters-specifically the subaperture, angular aperture, tilt angle, number of virtual sources, and frame rate-in partial aperture (subaperture compounding) and full aperture (steered compounding) fundamental mode cardiac imaging was thus investigated and compared. Field II simulation of a 3-D cylindrical annulus undergoing deformation and twist was developed to evaluate accuracy of 2-D strain estimation in cross-sectional views. The tradeoff between frame rate and number of virtual sources was then investigated via transthoracic imaging in the parasternal short-axis view of five healthy human subjects, using the strain filter to quantify estimation precision. Finally, the optimized subaperture compounding sequence (25-element subperture, 90° angular aperture, 10 virtual sources, 300-Hz frame rate) was compared to the optimized steered compounding sequence (60° angular aperture, 15° tilt, 10 virtual sources, 300-Hz frame rate) via transthoracic imaging of five healthy subjects. Both approaches were determined to estimate cumulative radial strain with statistically equivalent precision (subaperture compounding E(SNRe %) = 3.56, and steered compounding E(SNRe %) = 4.26).

Cardiac Lesion Mapping In Vivo Using Intracardiac Myocardial Elastography.

Radio frequency (RF) ablation of the myocardium is used to treat various cardiac arrhythmias. The size, spacing, and transmurality of lesions have been shown to affect the success of the ablation procedure; however, there is currently no method to directly image the size and formation of ablation lesions in real time. Intracardiac myocardial elastography (ME) has been previously used to image the decrease in cardiac strain during systole in the ablated region as a result of the lesion formation. However, the feasibility of imaging multiple lesions and identifying the presence of gaps between lesions has not yet been investigated. In this paper, RF ablation lesions ( ) were generated in the left ventricular epicardium in three anesthetized canines. Two sets of two lesions each were created in close proximity to one another with small gaps (1.5 and 4 cm), while one set of two lesions was created directly next to each other with no gap. A clinical intracardiac echocardiography system was programmed to transmit a custom diverging beam sequence at 600 Hz and used to image the ablation site before and after the induction of ablation lesions. Cumulative strains were estimated over systole using a normalized cross-correlational displacement algorithm and a least-squares strain kernel. Afterward, lesions were excised and subjected to tetrazolium chloride staining. Results indicate that intracardiac ME was capable of imaging the reduction in systolic strain associated with the formation of an ablation lesion. Furthermore, lesion sets containing gaps were able to be distinguished from lesion sets created with no gaps. These results indicate that the end-systolic strain measured using intracardiac ME may be used to image the formation of lesions induced during an RF ablation procedure, in order to provide critical assessment of lesion viability during the interventional procedure.

Non-invasive Characterization of Focal Arrhythmia with Electromechanical Wave Imaging in Vivo.

There is currently no established method for the non-invasive characterization of arrhythmia and differentiation between endocardial and epicardial triggers at the point of care. Electromechanical wave imaging (EWI) is a novel ultrasound-based imaging technique based on time-domain transient strain estimation that can map and characterize electromechanical activation in the heart in vivo. The objectives of this initial feasibility study were to determine that EWI is capable of differentiating between endocardial and epicardial sources of focal rhythm and, as a proof-of-concept, that EWI could characterize focal arrhythmia in one patient with premature ventricular contractions (PVCs) before radiofrequency (RF) ablation treatment. First, validation of EWI for differentiation of surface of origin was performed in seven (n = 7) adult dogs using four epicardial and four endocardial pacing protocols. Second, one (n = 1) adult patient diagnosed with PVC was imaged with EWI before the scheduled RF ablation procedure, and EWI results were compared with mapping procedure results. In dogs, EWI was capable of detecting whether pacing was of endocardial or epicardial origin in six of seven cases (86% success rate). In the PVC patient, EWI correctly identified both regions and surface of origin, as confirmed by results from the electrical mapping obtained from the RF ablation procedure. These results reveal that EWI can map the electromechanical activation across the myocardium and indicate that EWI could serve as a valuable pre-treatment planning tool in the clinic.

Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping.

Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.

Cardiac Strain Imaging With Coherent Compounding of Diverging Waves.

Current methods of cardiac strain imaging at high frame rate suffer from motion matching artifacts or poor lateral resolution. Coherent compounding has been shown to improve echocardiographic image quality while maintaining a high frame rate, but has never been used to image cardiac strain. However, myocardial velocity can have an impact on coherent compounding due to displacements between frames. The objective of this paper was to investigate the feasibility and performance of coherent compounding for cardiac strain imaging at a low and a high myocardial velocity. Left-ventricular contraction in short-axis view was modeled as an annulus with radial thickening and circumferential rotation. Simulated radio-frequency channel data with a cardiac phased array were obtained using three different beamforming methods: single diverging wave, coherent compounding of diverging waves, and conventional focusing. Axial and lateral displacements and strains as well as radial strains were estimated and compared to their true value. In vivo feasibility of cardiac strain imaging with coherent compounding was performed and compared to single diverging wave imaging. At low myocardial velocities, the axial, lateral, and radial strain relative error for nine compounded waves (16.3%, 40.4%, and 18.9%) were significantly lower than those obtained with single diverging wave imaging (19.9%, 80.3%, and 30.6%) and closer to that obtained with conventional focusing (16.7%, 43.7%, and 16%). In vivo left-ventricular radial strains exhibited higher quality with nine compounded waves than with single diverging wave imaging. These results indicate that cardiac strain can be imaged using coherent compounding of diverging waves with a better performance than with single diverging wave imaging while maintaining a high frame rate, and therefore, has the potential to improve diagnosis of myocardial strain-based cardiac diseases.

Evaluation of Coronary Artery Disease Using Myocardial Elastography with Diverging Wave Imaging: Validation against Myocardial Perfusion Imaging and Coronary Angiography.

Myocardial elastography (ME) is an ultrasound-based technique that can image 2-D myocardial strains. The objectives of this study were to illustrate that 2-D myocardial strains can be imaged with diverging wave imaging and differ, on average, between normal and coronary artery disease (CAD) patients. In this study, 66 patients with symptoms of CAD were imaged with myocardial elastography before a nuclear stress test or an invasive coronary angiography. Radial cumulative strains were estimated in all patients. The end-systolic radial strain in the total cross section of the myocardium was significantly higher in normal patients (17.9 ± 8.7%) than in patients with reversible perfusion defect (6.2 ± 9.3%, p < 0.001) and patients with significant (-0.9 ± 7.4%, p < 0.001) and non-significant (3.7 ± 5.7%, p < 0.01) lesions. End-systolic radial strain in the left anterior descending, left circumflex and right coronary artery territory was found to be significantly higher in normal patients than in CAD patients. These preliminary findings indicate that end-systolic radial strain measured with ME is higher on average in healthy persons than in CAD patients and that ME has the potential to be used for non-invasive, radiation-free early detection of CAD.

Electromechanical wave imaging (EWI) validation in all four cardiac chambers with 3D electroanatomic mapping in canines in vivo.

Characterization and mapping of arrhythmias is currently performed through invasive insertion and manipulation of cardiac catheters. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique, which tracks the electromechanical activation that immediately follows electrical activation. Electrical and electromechanical activations were previously found to be linearly correlated in the left ventricle, but the relationship has not yet been investigated in the three other chambers of the heart. The objective of this study was to investigate the relationship between electrical and electromechanical activations and validate EWI in all four chambers of the heart with conventional 3D electroanatomical mapping. Six (n = 6) normal adult canines were used in this study. The electrical activation sequence was mapped in all four chambers of the heart, both endocardially and epicardially using the St Jude's EnSite 3D mapping system (St. Jude Medical, Secaucus, NJ). EWI acquisitions were performed in all four chambers during normal sinus rhythm, and during pacing in the left ventricle. Isochrones of the electromechanical activation were generated from standard echocardiographic imaging views. Electrical and electromechanical activation maps were co-registered and compared, and electrical and electromechanical activation times were plotted against each other and linear regression was performed for each pair of activation maps. Electromechanical and electrical activations were found to be directly correlated with slopes of the correlation ranging from 0.77 to 1.83, electromechanical delays between 9 and 58 ms and R 2 values from 0.71 to 0.92. The linear correlation between electrical and electromechanical activations and the agreement between the activation maps indicate that the electromechanical activation follows the pattern of propagation of the electrical activation. This suggests that EWI may be used as a novel non-invasive method to accurately characterize and localize sources of arrhythmias.

Validation of electromechanical wave imaging in a canine model during pacing and sinus rhythm.

BACKGROUND: Accurate determination of regional areas of arrhythmic triggers is of key interest to diagnose arrhythmias and optimize their treatment. Electromechanical wave imaging (EWI) is an ultrasound technique that can image the transient deformation in the myocardium after electrical activation and therefore has the potential to detect and characterize location of triggers of arrhythmias. OBJECTIVES: The objectives of this study were to investigate the relationship between the electromechanical and the electrical activation of the left ventricular (LV) endocardial surface during epicardial and endocardial pacing and during sinus rhythm as well as to map the distribution of electromechanical delays. METHODS: In this study, 6 canines were investigated. Two external electrodes were sutured onto the epicardial surface of the LV. A 64-electrode basket catheter was inserted through the apex of the LV. Ultrasound channel data were acquired at 2000 frames/s during epicardial and endocardial pacing and during sinus rhythm. Electromechanical and electrical activation maps were synchronously obtained from the ultrasound data and the basket catheter, respectively. RESULTS: The mean correlation coefficient between electromechanical and electrical activation was 0.81 for epicardial anterior pacing, 0.79 for epicardial lateral pacing, 0.69 for endocardial pacing, and 0.56 for sinus rhythm. CONCLUSION: The electromechanical activation sequence determined by EWI follows the electrical activation sequence and more specifically in the case of pacing. This finding is of key interest in the role that EWI can play in the detection of the anatomical source of arrhythmias and the planning of pacing therapies such as cardiovascular resynchronization therapy.

Real-time Monitoring of High Intensity Focused Ultrasound (HIFU) Ablation of In Vitro Canine Livers Using Harmonic Motion Imaging for Focused Ultrasound (HMIFU).

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a technique that can perform and monitor high-intensity focused ultrasound (HIFU) ablation. An oscillatory motion is generated at the focus of a 93-element and 4.5 MHz center frequency HIFU transducer by applying a 25 Hz amplitude-modulated signal using a function generator. A 64-element and 2.5 MHz imaging transducer with 68kPa peak pressure is confocally placed at the center of the HIFU transducer to acquire the radio-frequency (RF) channel data. In this protocol, real-time monitoring of thermal ablation using HIFU with an acoustic power of 7 W on canine livers in vitro is described. HIFU treatment is applied on the tissue during 2 min and the ablated region is imaged in real-time using diverging or plane wave imaging up to 1,000 frames/second. The matrix of RF channel data is multiplied by a sparse matrix for image reconstruction. The reconstructed field of view is of 90° for diverging wave and 20 mm for plane wave imaging and the data are sampled at 80 MHz. The reconstruction is performed on a Graphical Processing Unit (GPU) in order to image in real-time at a 4.5 display frame rate. 1-D normalized cross-correlation of the reconstructed RF data is used to estimate axial displacements in the focal region. The magnitude of the peak-to-peak displacement at the focal depth decreases during the thermal ablation which denotes stiffening of the tissue due to the formation of a lesion. The displacement signal-to-noise ratio (SNRd) at the focal area for plane wave was 1.4 times higher than for diverging wave showing that plane wave imaging appears to produce better displacement maps quality for HMIFU than diverging wave imaging.

Intracardiac myocardial elastography in canines and humans in vivo.

Intracardiac echocardiography (ICE) is a useful imaging modality which is used during RF ablation procedures to identify anatomical structures. Utilizing ICE in conjunction with myocardial elastography (ME) can provide additional information on the mechanical properties of cardiac tissue and provide information on mechanical changes caused by ablation. The objective of this study was to demonstrate that ICE can be used at high frame rate using a diverging beam transmit sequence to image myocardial strain and differentiate myocardial tissue properties before, during, and after ablation for a clinical ablation procedure. In this feasibility study, three normal canines and eight patients with atrial fibrillation (AF) were studied in vivo. A 5.8-MHz ICE transducer was used to image the heart with a diverging beam transmit method achieving 1200 frames per second (fps). Cumulative axial displacement estimation was performed using 1-D cross-correlation with a window size of 2.7 mm and 95% overlap. Axial cumulative strains were estimated in the left atrium (LA) and right atrium (RA) using a least-squares estimator with a kernel of 2 mm on the axial displacements. In the canine case, radial thickening was detected in the lateral wall and in the interatrial septum during LA emptying. For AF patients, the mean absolute strain in the ablated region was lower (6.7 ± 3.1%) than before the ablation (17.4 ± 9.3%) in LA at the end of the LA emptying phase. In the cavotricuspid isthmus (CTI) region, mean absolute strain magnitude at the end of the RA emptying phase was found to be higher during ablation (43.0 ± 18.1%) compared with after ablation (33.7 ± 15.8%). Myocardial strains in the LA of an AF patient were approximately 2.6 times lower in the ablated region than before ablation. This initial feasibility indicates that ME can be used as a new imaging modality in conjunction with ICE in RF ablation guidance and lesion monitoring.

Atrial electromechanical cycle length mapping in paced canine hearts in vivo.

Atrial arrhythmias affect millions of people worldwide. Characterization and study of arrhythmias in the atria in the clinic is currently performed point by point using mapping catheters capable of generating maps of the electrical activation rate or cycle length. In this paper, we describe a new ultrasound-based mapping technique called electromechanical cycle length mapping (ECLM) capable of estimating the electromechanical activation rate, or cycle length, i.e., the rate of the mechanical activation of the myocardium which follows the electrical activation. ECLM relies on frequency analysis of the incremental strain within the atria and can be performed in a single acquisition. ECLM was validated in a canine model paced from the left atrial appendage, against pacing rates within the reported range of cycle lengths previously measured during atrial arrhythmias such as atrial fibrillation. Correlation between the global estimated electromechanical cycle lengths and pacing rates was shown to be excellent (slope = 0.983, intercept = 3.91, r(2) = 0.9999). The effect of the number of cardiac cycles on the performance of ECLM was also investigated and the reproducibility of ECLM was demonstrated (error between consecutive acquisitions for all pacing rates: 6.3 ± 4.3%). These findings indicate the potential of ECLM for noninvasively characterizing atrial arrhythmias and provide feedback on the treatment planning of catheter ablation procedures in the clinic.

Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI).

Noninvasive measurement of mechanical properties of biological tissues in vivo could play a significant role in improving the current understanding of tissue biomechanics. In this study, we propose a method for measuring elastic properties non-invasively by using internal indentation as generated by harmonic motion imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a focused ultrasound transducer at the focal region, and the resulting displacements are estimated by tracking radiofrequency signals acquired by an imaging transducer. In this study, the focal spot region was modeled as a rigid cylindrical piston that exerts an oscillatory, uniform internal force to the underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the applied force to the axial strain measured by 1D ultrasound imaging. The accuracy and the precision of the EHMI estimate were assessed both numerically and experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility of this method in soft tissues was also shown in canine liver specimens in vitro. Very good correlation and agreement was found between the measured Young's modulus and the HMI modulus in the numerical study (r(2) > 0.99, relative error <10%) and on polyacrylamide gels (r(2) = 0.95, relative error <24%). The average HMI modulus on five liver samples was found to EHMI = 2.62  ±  0.41 kPa, compared to EMechTesting = 4.2  ±  2.58 kPa measured by rheometry. This study has demonstrated for the first time the initial feasibility of a non-invasive, model-independent method to estimate local elastic properties of biological tissues at a submillimeter scale using an internal indentation-like approach. Ongoing studies include in vitro experiments in a larger number of samples and feasibility testing in in vivo models as well as pathological human specimens.