A Pilot Study on Novel Use of Color Doppler Imaging for Navigation of Wiring in Coronary Interventions.

OBJECTIVE: To test the Doppler guide wire (DGW) for navigation of the wire positioning by color Doppler ultrasound in the setting of percutaneous coronary intervention (PCI). METHODS: An acoustically active DGW was tested in a water tank before its in vivo use. A waveform generator was connected to the DGW, and a transducer scanned the DGW to visualize a Doppler shift signal between the vibrating piezoelectric crystal located at the DGW tip and Doppler signal from the transducer as a distinct, instantaneous color marker. An intracoronary injection was tested in four male domestic pigs using an open-chest setting. A Judkins left coronary guiding catheter was inserted into the ascending aorta via the right carotid artery under B-mode ultrasound guidance. The DGW with an infusion catheter or over-the-wire (OTW) balloon catheter was inserted into the guiding catheter. The color marker instantaneously defined the DGW tip and navigated the catheter into the left anterior descending artery (LAD). RESULTS: The tip of the DGW was visualized within the guiding catheter by a distinct color marker and helped to engage the guiding catheter to the left main orifice. The DGW with an infusion or OTW balloon catheter was inserted into the LAD. We confirmed that the catheter was positioned in the proximal LAD by the colored territory perfused by an injected indigo carmine solution. CONCLUSION: Ultrasound navigation using acoustically active DGW was feasible. Our pilot study introduces a new concept of color Doppler-navigated wire positioning in the coronary artery in the setting of PCI.

A learning-based, region of interest-tracking algorithm for catheter detection in echocardiography.

Echocardiography (echo) is gaining popularity to guide the catheter during surgical procedures. However, it is difficult to discern the catheter tip in echo even with an acoustically active catheter. An acoustically active catheter is detected for the first time in cardiac echo images using two methods. First, a convolutional neural network (CNN) model was trained to detect the region of interest (ROI), the interior of the left ventricle, containing the catheter tip. Color intensity difference detection technique was implemented on the ROI to detect the catheter. This method succeeded in detecting the catheter without any manual input on 94% and 57% of long- and short-axis projections, respectively. Second, several tracking methods were implemented and tested. Given the manually identified initial positions of the catheter, the tracking methods could distinguish between the target (catheter tip) and the surrounding on the rest of the frames. Combining the two techniques, for the first time, resulted in an automatic, robust, and fast method for catheter detection in echo images.

Doppler-Guided Acoustically Active Injection Catheter: Transendocardial Delivery Assessed by an Efficacy Testing Animal Model.

Percutaneous transendocardial injections of therapeutic agents into the myocardium may not always be effective. We used an animal model for assessing the efficacy of the injections using linoleic acid as a testing agent. Efficacious delivery into the myocardium of a beating heart was indicated by rapidly developed local myocardial necrosis and wall motion abnormalities using echocardiography. We employed this experimental model to test our innovative technology, an acoustically active injection catheter. The Doppler ultrasound-guided acoustically active injection catheter effectively delivers the substance to the myocardium but needs further technical improvements to minimize an unwanted systemic distribution of the agent.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Automatic segmentation of the left ventricle in echocardiographic images using convolutional neural networks.

BACKGROUND: Two-dimensional echocardiography (2D echo) is the most widely used non-invasive imaging modality due to its fast acquisition time, low cost, and high temporal resolution. Boundary identification of left ventricle (LV) in 2D echo, i.e., image segmentation, is the first step to calculate relevant clinical parameters. Currently, LV segmentation in 2D echo is primarily conducted semi-manually. A fully-automatic segmentation of the LV wall needs further development. METHODS: We evaluated the performance of the state-of-the-art convolutional neural networks (CNNs) for the segmentation of 2D echo images from 6 standard projections of the LV. We used two segmentation algorithms: U-net and segAN. The models were trained using an in-house dataset, which consists of 1,649 porcine images from 6 to 8 different pigs. In addition, a transfer learning approach was used for the segmentation of long-axis projections by training models with our database based on the previously trained weights obtained from Cardiac Acquisitions for Multi-structure Ultrasound Segmentation (CAMUS) dataset. The models were tested on a separate set of images from two other pigs by computing several metrics. The segmentation process was combined with a 3D reconstruction framework to quantify the physiological indices such as LV volumes and ejection fraction (EF). RESULTS: The average dice metric for the LV cavity was 0.90 and 0.91 for the U-net and segAN, respectively, which was higher than 0.82 for the level-set (P value: 3.31×10-25). The average Hausdorff distance for the LV cavity was 2.71 mm and 2.82 mm for the U-net and segAN, respectively, which was lower than 3.64 mm for the level-set (P value: 4.86×10-16). The LV shapes and volumes obtained using the CNN segmentation models were in good agreement with the results segmented by the experts. In addition, the differences of the calculated physiological parameters between two 3D reconstruction models segmented by the experts and CNNs were less than 15%. CONCLUSIONS: The results showed that both CNN models achieve higher performance on LV segmentation than the level-set method. The error of the reconstruction from automatic segmentation compared to the expert segmentation is less than 15%, which is within the 20% error of echo compared to the gold standard.

A hybrid echocardiography-CFD framework for ventricular flow simulations.

Image-based CFD is a powerful tool to study cardiovascular flows while 2D echocardiography (echo) is the most widely used noninvasive imaging modality for the diagnosis of heart disease. Here, echo is combined with CFD, that is, an echo-CFD framework, to study ventricular flows. To achieve this, the previous 3D reconstruction from multiple 2D echo at standard cross sections is extended by: (a) reconstructing aortic and mitral valves from 2D echo and closing the left-ventricle (LV) geometry by approximating a superior wall; (b) incorporating the physiological assumption of the fixed apex as a reference (fixed) point in the 3D reconstruction; and (c) incorporating several smoothing algorithms to remove the nonphysical oscillations (ringing) near the basal section. The method is applied to echo from a baseline LV and one after inducing acute myocardial ischemia (AMI). The 3D reconstruction is validated by comparing it against a reference reconstruction from many echo sections while flow simulations are validated against the Doppler ultrasound velocity measurements. The sensitivity study shows that the choice of the smoothing algorithm does not change the flow pattern inside the LV. However, the presence of the mitral valve can significantly change the flow pattern during the diastole phase. In addition, the abnormal shape of a LV with AMI can drastically change the flow during diastole. Furthermore, the hemodynamic energy loss, as an indicator of the LV pumping performance, for different test cases is calculated, which shows a larger energy loss for a LV with AMI compared to the baseline one.

Thermodynamic interference with bile acid demicelleization reduces systemic entry and injury during cholestasis.

Bile acids (BA), with their large hydrophobic steroid nucleus and polar groups are amphipathic molecules. In bile, these exist as micelles above their critical micellar concentration (CMC). In blood at low concentrations, these exist as monomers, initiating cellular signals. This micellar to monomer transition may involve complex thermodynamic interactions between bile salts alone or with phospholipids, i.e. mixed micelles and the aqueous environment. We therefore went on to test if therapeutically relevant changes in temperature could influence micellar behavior of bile salts, and in turn whether this affected the biological responses in cells, and in vivo. Sodium taurocholate (STC) belongs to a major class of bile salts. STC has a CMC in the 5-8 mM range and its infusion into the pancreatic duct is commonly used to study pancreatitis. We thus studied micellar breakdown of STC using isothermal titration calorimetry (ITC), dynamic light scattering and cryogenic transmission electron microscopy. Under conditions relevant to the in vivo environment (pH 7.4, Na 0.15 M), ITC showed STC to have a U shaped reduction in micellar breakdown between 37 °C and 15 °C with a nadir at 25 °C approaching ≈90% inhibition. This temperature dependence paralleled pancreatic acinar injury induced by monomeric STC. Mixed micelles of STC and 1-palmitoyl, 2-oleyl phosphatidylcholine, a phospholipid present in high proportions in bile, behaved similarly, with ≈75% reduction in micellar breakdown at 25 °C compared to 37 °C. In vivo pancreatic cooling to 25 °C reduced the increase in circulating BAs after infusion of 120 mM (5%) STC into the pancreatic duct, and duct ligation. Lower BA levels were associated with improved cardiac function, reduced myocardial damage, shock, lung injury and improved survival independent of pancreatic injury. Thus micellar breakdown of bile salts is essential for their entry into the systemic circulation, and thermodynamic interference with this may reduce their systemic entry and consequent injury during cholestasis, such as from biliary pancreatitis.

Real-Time Visualization of an Acoustically Active Injection Catheter With Ultrasound Imaging: Algorithm and In Vivo Validation in a Swine Model.

OBJECTIVE: To independently visualize a catheter and needle during minimally invasive surgery in order to aid in precisely guiding them to their intended location. METHODS: Symmetric frequency detection allows for the visualization of the acoustically active catheter tip as a unique color in live imaging. This study extends the algorithm to identify two different crystals by unique colors, validating the algorithm with in vivo pig experiments while simulating the human condition using different attenuation pads. RESULTS: The catheter and needle tip were identified with unique colors, differentiable from common Doppler colors, with a frame rate varying between 8 and 10 Hz. Both were visible at graded levels of attenuation induced by interposed polymer pads. Reducing ensemble length increased the frame rate and decreased the signal-to-noise ratio (SNR), though not significantly. At the highest in-path attenuation of 12 dB at 5 MHz, the catheter spot marker was visible whereas the needle was not. The SNR of the catheter signal varied between 12.50 and 18.24 dB and the size of the spot marker varied between 149 and 1015 mm2. The SNR of the needle signal varied between 6.37 and 16.3 dB and the size of the spot marker between 59 and 169 mm2. A reliability index greater than 50% was achieved for all cases except for the needle crystal at the highest attenuation setting. CONCLUSION: Modified symmetric frequency detection algorithm can uniquely visualize both catheter and needle in real time with in-path attenuation. SIGNIFICANCE: Unambiguous and distinct visualization of separate locations on the catheter facilitates real-time tracking of minimally invasive procedures.

A Real-time Color Doppler Marker for Echocardiographic Guidance of an Acoustically Active Extracorporeal Membrane Oxygenation Cannula.

B-mode ultrasound imaging guidance of cannulas can be compromised by noise, artifacts, and echogenicity that is not distinctive from that of surrounding anatomy. We have modified a venovenous extracorporeal membrane oxygenation cannula by embedding piezoelectric crystals into each of its 3 blood flow ports. Each vibrating crystal acoustically interacts with a Doppler imaging signal and produces an instantaneous color marker. The aim of this study was to compare identification of the extracorporeal membrane oxygenation cannula ports by B-mode imaging versus the color Doppler marker. Unlike B-mode imaging, the color Doppler marker identified the corresponding port even in highly challenging closed-chest scans in anesthetized pigs. The method could improve guidance accuracy of cannulas by ultrasound scans.

Unambiguous Identification and Visualization of an Acoustically Active Catheter by Ultrasound Imaging in Real Time: Theory, Algorithm, and Phantom Experiments.

OBJECTIVE: Ultrasound-guided biopsies and minimally invasive procedures have been used in numerous medical applications, including catheter guidance. The biggest challenge for catheter guidance by ultrasound lies in distinguishing the catheter from neighboring tissue, as well as the ability to differentiate the catheter body from its tip. METHODS: In our previous work, we introduced a functional prototype of an acoustically active catheter, in which a miniature piezoelectric crystal allowed accurate localization of the catheter tip by pulsed wave (PW) Doppler imaging and Doppler spectrogram. In this paper, the theory behind the symmetric Doppler shift due to the interaction of ultrasound wave with a vibrating piezoelectric crystal is explained. The theory is validated in an experimental continuous flow phantom setup. A novel algorithm, symmetric frequency detection algorithm, is presented for identification and visualization of the catheter tip in real time along with B-mode and PW Doppler. RESULTS: The catheter tip is identified with a distinct color differentiable from common Doppler colors with a frame rate varying from 22 to 50 Hz. The catheter tip can be visualized in a small region of 2.4 mm in the elevational direction. CONCLUSION: The algorithm can be implemented in most clinical ultrasound machines with minor additions to the PW Doppler processing algorithm. The algorithm is optimized to be robust for a variety of blood flow velocities and is shown to perform well when the signal from the blood is on par in amplitude with the catheter signal. SIGNIFICANCE: Unambiguous and distinct visualization of catheter tip facilitates real-time tracking of the catheter and aids minimally invasive procedures.

An Interposed Pad in Open-Chest Echocardiographic Porcine Scans for Mimicking Ultrasound Signal Attenuation in a Human Chest.

Opening a chest in an experimental echocardiographic animal study eliminates ultrasound signal attenuation by the chest wall. We developed a scanning technique that involves the use of an attenuative pad created from a mixture of urethane and titanium dioxide. The pad was interposed within transmission gel between the transducer face and cardiac surface in open-chest scans in a porcine model. Comparative measurements of left ventricular echogenicity without and with the pad demonstrate that the pad reproducibly causes ultrasound signal attenuation that closely mimics chest attenuation in clinical transthoracic echocardiographic studies.

Left Ventricular Septal Hypertrophy in Elderly Patients With Aortic Stenosis.

OBJECTIVES: Left ventricular (LV) septal hypertrophy in aortic stenosis raises diagnostic and therapeutic questions. However, the etiology and clinical consequences of this finding have not been well studied. The aim of this study was to perform a morphologic evaluation of the LV in aortic stenosis and to investigate the contributing factors and consequences of septal hypertrophy. METHODS: Patients with moderate or severe aortic stenosis were prospectively enrolled. Patients with previous myocardial infarction, wall motion abnormalities, at least moderate valvular regurgitation, known cardiomyopathy, an LV ejection fraction of less than 50%, and age younger than 65 years were excluded. RESULTS: Forty-one patients underwent a final analysis. Septal hypertrophy (LV septal wall thickness ≥15 mm) was confirmed in 21 of 41 patients. The septal hypertrophy group had higher peak aortic valve velocity, a higher diabetes mellitus rate, and a higher rate and longer duration of hypertension than those without septal hypertrophy. The peak aortic valve velocity (odds ratio, 7.1; 95% confidence interval, 1.4-37.1) and diabetes mellitus (odds ratio, 7.4; 95% confidence interval, 1.2-46.2) were the significant factors associated with septal hypertrophy by multivariate analysis. Intraventricular conduction disturbance on electrocardiography was more frequent in the septal hypertrophy group (P = .021). CONCLUSIONS: Left ventricular septal hypertrophy was commonly observed in elderly patients with aortic stenosis, and a higher aortic valve velocity, hypertension, and diabetes mellitus were associated factors. Intraventricular conduction disturbance occurred more often in patients with septal hypertrophy than those without, which implies the pathophysiologic consequence. Further studies are needed to determine the impact of septal hypertrophy and intraventricular conduction disturbance on the prognosis of patients after aortic valve interventions.

Acoustically Active Catheter for Intracardiac Navigation by Color Doppler Ultrasonography.

Navigation of intracardiac catheters by echocardiography is challenging because of the fundamental limitations of B-mode ultrasonography. We describe a catheter fitted with a piezoelectric crystal, which vibrates and produces an instantaneous marker in color flow Doppler scans. The navigation learning curve was explored first in six pigs. Accuracy and precision of targeting with the navigation marker "off" (i.e., B-mode imaging) and "on" were assessed in another six pigs. Paired comparisons confirmed significantly (p = 0.04) shorter mean distances achieved in each pig with the color Doppler marker. Pooled (mean ± standard deviation) distance of the catheter tip from the target crystal was 5.27 ± 1.62 mm by B-mode guidance and 3.66 ± 1.45 mm by color Doppler marker navigation. Dye injection targeted into the ischemic border zone was successful in 8 of 10 pigs. Intracardiac catheter navigation with color Doppler ultrasonography is more accurate compared with conventional guidance by B-mode imaging.

Automated Three-Dimensional Reconstruction of the Left Ventricle From Multiple-Axis Echocardiography.

Two-dimensional echocardiography (echo) is the method of choice for noninvasive evaluation of the left ventricle (LV) function owing to its low cost, fast acquisition time, and high temporal resolution. However, it only provides the LV boundaries in discrete 2D planes, and the 3D LV geometry needs to be reconstructed from those planes to quantify LV wall motion, acceleration, and strain, or to carry out flow simulations. An automated method is developed for the reconstruction of the 3D LV endocardial surface using echo from a few standard cross sections, in contrast with the previous work that has used a series of 2D scans in a linear or rotational manner for 3D reconstruction. The concept is based on a generalized approach so that the number or type (long-axis (LA) or short-axis (SA)) of sectional data is not constrained. The location of the cross sections is optimized to minimize the difference between the reconstructed and measured cross sections, and the reconstructed LV surface is meshed in a standard format. Temporal smoothing is implemented to smooth the motion of the LV and the flow rate. This software tool can be used with existing clinical 2D echo systems to reconstruct the 3D LV geometry and motion to quantify the regional akinesis/dyskinesis, 3D strain, acceleration, and velocities, or to be used in ventricular flow simulations.

Effects of Bileaflet Mechanical Mitral Valve Rotational Orientation on Left Ventricular Flow Conditions.

We studied left ventricular flow patterns for a range of rotational orientations of a bileaflet mechanical heart valve (MHV) implanted in the mitral position of an elastic model of a beating left ventricle (LV). The valve was rotated through 3 angular positions (0, 45, and 90 degrees) about the LV long axis. Ultrasound scans of the elastic LV were obtained in four apical 2-dimensional (2D) imaging projections, each with 45 degrees of separation. Particle imaging velocimetry was performed during the diastolic period to quantify the in-plane velocity field obtained by computer tracking of diluted microbubbles in the acquired ultrasound projections. The resulting velocity field, vorticity, and shear stresses were statistically significantly altered by angular positioning of the mechanical valve, although the results did not show any specific trend with the valve angular position and were highly dependent on the orientation of the imaging plane with respect to the valve. We conclude that bileaflet MHV orientation influences hemodynamics of LV filling. However, determination of 'optimal' valve orientation cannot be made without measurement techniques that account for the highly 3-dimensional (3D) intraventricular flow.

Does valvuloarterial impedance impact prognosis after surgery for severe aortic stenosis in the elderly?

BACKGROUND: Valvuloarterial impedance (Zva) was introduced as a prognostic measure in patients with aortic stenosis (AS). However, it is unclear whether Zva has a prognostic impact on survival after surgical aortic valve replacement (AVR) in patients with severe AS with preserved ejection fraction (EF). METHODS: We retrospectively reviewed 929 consecutive patients who had AVR. We investigated 170 elderly patients (age >65 years, mean 76 years) who had AVR secondary to severe AS (mean gradient ≥40 mm Hg; aortic valve area ≤1 cm(2); peak velocity ≥4 m/s). Patients with EF <50%, greater than moderate aortic regurgitation, prior heart surgery and concomitant mitral or tricuspid valve surgery were excluded. Zva was calculated and the patients were divided into two groups; low Zva, Zva <4.3 (n=82) and high Zva, Zva ≥4.3 (n=88). The end point was all-cause of death. Survival curves were calculated according to Kaplan-Meier method. RESULTS: Age, prevalence of hypertension, diabetes, chronic kidney disease (CKD), atrial fibrillation, symptoms, EF, E/e' and concomitant coronary artery bypass graft were not different between the groups. Survival was not different between the groups at 5 years (70% in low Zva and 81% in high Zva; p=0.21) and for the entire follow-up period (p=0.23). Only age was a significant factor in predicting survival by multivariate analyses in Cox proportional hazards model after adjusting for Zva, CKD, atrial fibrillation and hypertension. CONCLUSIONS: Our results suggest that preoperative Zva does not have a prognostic impact on postoperative survival in elderly patients with severe AS with preserved EF. Further investigation is needed to elucidate the controversial results.

Bachmann's bundle and coronary sinus ostial pacing accentuate left atrial electrical dyssynchrony in an acute canine model.

INTRODUCTION: In patients with intraatrial conduction delay and sinus node (SN) dysfunction, pacing Bachmann's bundle (BBR) and coronary sinus ostium (CSO) has been suggested to achieve atrial resynchronization with potential beneficial impact on atrial fibrillation and diastolic heart failure. Clinical studies have not shown superiority of one approach. METHODS AND RESULTS: We studied electrical activation sequence in an open-chest acute canine model of normal atrial function in 8 mongrel dogs under general anesthesia. Bipolar plunge electrodes were distributed over the surface of the atria during unifocal pacing, and intracardiac activation sequence was observed. SN pacing resulted in near-simultaneous activation at midline sites (BBR and CSO); the left atrium (LA) was activated by anterior and posterior wavefronts simultaneously propagating septally to laterally and meeting at the low-lateral perimitral LA. Right atrial appendage (RAA) pacing created intra-RA conduction delay and delayed onset of LA activation. Pacing from RAA, CSO, and BBR resulted in nonsimultaneous activation at midline sites and produced an anteroposterior gradient of LA activation. This phenomenon was seen to the greatest degree with midline pacing and shifted the site of latest activation away from the low-lateral perimitral LA in all pacing configurations except SN pacing. CONCLUSION: Pacing-induced intra-LA activation dispersion is enhanced with midline atrial pacing, and secondarily shifts the site of latest activation away from the lateral mitral annulus. Measuring atrial activation times to the low-lateral perimitral LA can underestimate the degree of atrial dyssynchrony and be misinterpreted as atrial synchrony. Establishing clinical impact requires evaluation of human data.

Acoustically active injection catheter guided by ultrasound: navigation tests in acutely ischemic porcine hearts.

Catheters are increasingly used therapeutically and investigatively. With complex usage comes a need for more accurate intracardiac localization than traditional guidance can provide. An injection catheter navigated by ultrasound was designed and then tested in an open-chest model of acute ischemia in eight pigs. The catheter is made "acoustically active" by a piezo-electric crystal near its tip, electronically controlled, vibrating in the audio frequency range and uniquely identifiable using pulsed-wave Doppler. Another "target" crystal was sutured to the epicardium within the ischemic region. Sonomicrometry was used to measure distances between the two crystals and then compared with measurements from 2-D echocardiographic images. Complete data were obtained from seven pigs, and the correlation between sonomicrometry and ultrasound measurements was excellent (p < 0.0001, ρ = 0.9820), as was the intraclass correlation coefficient (0.96) between two observers. These initial experimental results suggest high accuracy of ultrasound navigation of the acoustically active catheter prototype located inside the beating left ventricle.

Motion analysis of right ventricular dysfunction under mild or moderate pressure overload caused by acute pulmonary embolism.

Acute pulmonary embolism (APE) is the third most common cause of death in the United States. Appearing as a sudden blockage in a major pulmonary artery, APE may cause mild, moderate or severe right ventricular (RV) overload. Although severe RV overload produces diagnostically obvious RV mechanical failure, little progress has been made in gaining a clinical and biophysical understanding of moderate and mild acute RV overload and its impact on RV functionality. In the research described here, we conducted a pilot study in pigs using echocardiography and observed the following abnormalities in RV functionality under acute mild or moderate RV overload: (i) occurrence of paradoxical septal motion with "waving" dynamics; (ii) decrease in local curvature of the septum (p < 0.01); (iii) lower positive correlation between movement of the RV free wall and movement of the septum (p < 0.05); (iv) slower rate of RV fractional area change (p < 0.05); and (v) decrease in movement stability, particularly in the middle of the septum (p < 0.05).

Left ventricular flow analysis: recent advances in numerical methods and applications in cardiac ultrasound.

The left ventricle (LV) pumps oxygenated blood from the lungs to the rest of the body through systemic circulation. The efficiency of such a pumping function is dependent on blood flow within the LV chamber. It is therefore crucial to accurately characterize LV hemodynamics. Improved understanding of LV hemodynamics is expected to provide important clinical diagnostic and prognostic information. We review the recent advances in numerical and experimental methods for characterizing LV flows and focus on analysis of intraventricular flow fields by echocardiographic particle image velocimetry (echo-PIV), due to its potential for broad and practical utility. Future research directions to advance patient-specific LV simulations include development of methods capable of resolving heart valves, higher temporal resolution, automated generation of three-dimensional (3D) geometry, and incorporating actual flow measurements into the numerical solution of the 3D cardiovascular fluid dynamics.