Saurabh Datta

Ultrasound-enhanced thrombolysis using Definity® as a cavitation nucleation agent

Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity, was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity. A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p < 0.0001, n = 24). The largest mean penetration depth of rt-PA (222 microm) and plasminogen (241 microm) was observed in the presence of stable cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

Passive cavitation imaging with ultrasound arrays

A method is presented for passive imaging of cavitational acoustic emissions using an ultrasound array, with potential application in real-time monitoring of ultrasound ablation. To create such images, microbubble emissions were passively sensed by an imaging array and dynamically focused at multiple depths. In this paper, an analytic expression for a passive image is obtained by solving the Rayleigh-Sommerfield integral, under the Fresnel approximation, and passive images were simulated. A 192-element array was used to create passive images, in real time, from 520-kHz ultrasound scattered by a 1-mm steel wire. Azimuthal positions of this target were accurately estimated from the passive images. Next, stable and inertial cavitation was passively imaged in saline solution sonicated at 520 kHz. Bubble clusters formed in the saline samples were consistently located on both passive images and B-scans. Passive images were also created using broadband emissions from bovine liver sonicated at 2.2 MHz. Agreement was found between the images and source beam shape, indicating an ability to map therapeutic ultrasound beams in situ. The relation between these broadband emissions, sonication amplitude, and exposure conditions are discussed.

Automated quantification of mitral inflow and aortic outflow stroke volumes by three-dimensional real-time volume color-flow Doppler transthoracic echocardiography: comparison with pulsed-wave Doppler and cardiac magnetic resonance imaging.

BACKGROUND The aim of this study was to compare the feasibility, accuracy, and reproducibility of automated quantification of mitral inflow and aortic stroke volumes (SVs) using real-time three-dimensional volume color-flow Doppler transthoracic echocardiography (RT-VCFD), with cardiac magnetic resonance (CMR) imaging as the reference method. METHODS In 44 patients (86% of the screened patients) without valvular disease, RT-VCFD, CMR left ventricular short-axis cines and aortic phase-contrast flow measurement and two-dimensional (2D) transthoracic echocardiography (TTE) were performed. Dedicated software was used to automatically measure mitral inflow and aortic SVs with RT-VCFD. CMR total SV was calculated using planimetry of short-axis slices and aortic SV by phase-contrast imaging. SVs by 2D TTE were computed in the conventional manner. RESULTS The mean age of the included patients was 40 ± 16 years, and the mean left ventricular ejection fraction was 61 ± 9%. Automated flow measurements were feasible in all study patients. Mitral inflow SV by 2D TTE and RT-VCFD were 85.0 ± 21.5 and 94.5 ± 22.0 mL, respectively, while total SV by CMR was 95.6 ± 22.7 mL (P < .001, analysis of variance). On post hoc analysis, mitral inflow SV by RT-VCFD was not different from the CMR value (P = .99), while SV on 2D TTE was underestimated (P = .001). The respective aortic SVs were 82.8 ± 22.3, 94.2 ± 22.3, and 93.4 ± 24.6 mL (P < .001). On post hoc analysis, aortic SV by RT-VCFD was not different from the CMR value (P = .99), while SV on 2D TTE was underestimated (P = .006). The interobserver variability for SV measurements was significantly worse for 2D TTE compared with RT-VCFD. CONCLUSIONS RT-VCFD imaging with an automated quantification algorithm is feasible, accurate, and reproducible for the measurement of mitral inflow and aortic SVs and is superior to manual 2D TTE-based measurements. The rapid and automated measurements make this technique practical in the clinical setting to measure and report SVs routinely where the acoustic window will allow it, which was 86% in our study.

Quantification of chronic functional mitral regurgitation by automated 3-dimensional peak and integrated proximal isovelocity surface area and stroke volume techniques using real-time 3-dimensional volume color doppler echocardiography: In vitro and clinical validation

Background—The aim of this study was to test the accuracy of an automated 3-dimensional (3D) proximal isovelocity surface area (PISA) (in vitro and patients) and stroke volume technique (patients) to assess mitral regurgitation (MR) severity using real-time volume color flow Doppler transthoracic echocardiography. Methods and Results—Using an in vitro model of MR, the effective regurgitant orifice area and regurgitant volume (RVol) were measured by the PISA technique using 2-dimensional (2D) and 3D (automated true 3D PISA) transthoracic echocardiography. The mean anatomic regurgitant orifice area (0.35±0.10 cm2) was underestimated to a greater degree by the 2D (0.12±0.05 cm2) than the 3D method (0.25±0.10 cm2; P<0.001 for both). Compared with the flowmeter (40±14 mL), the RVol by 2D PISA (20±19 mL) was underestimated (P<0.001), but the 3D peak (43±16 mL) and integrated PISA-based (38±14 mL) RVol were comparable (P>0.05 for both). In patients (n=30, functional MR), 3D effective regurgitant orifice area correlated well with cardiac magnetic resonance imaging RVol r=0.84 and regurgitant fraction r=0.80. Compared with cardiac magnetic resonance imaging RVol (33±22 mL), the integrated PISA RVol (34±26 mL; P=0.42) was not significantly different; however, the peak PISA RVol was higher (48±27 mL; P<0.001). In addition, RVol calculated as the difference in automated mitral and aortic stroke volumes by real-time 3D volume color flow Doppler echocardiography was not significantly different from cardiac magnetic resonance imaging (34±21 versus 33±22 mL; P=0.33). Conclusions—Automated real-time 3D volume color flow Doppler based 3D PISA is more accurate than the 2D PISA method to quantify MR. In patients with functional MR, the 3D RVol by integrated PISA is more accurate than a peak PISA technique. Automated 3D stroke volume measurement can also be used as an adjunctive method to quantify MR severity.

Acoustic emissions during 3.1 MHz ultrasound bulk ablation in vitro

Acoustic emissions associated with cavitation and other bubble activity have previously been observed during ultrasound (US) ablation experiments. Because detectable bubble activity may be related to temperature, tissue state and sonication characteristics, these acoustic emissions are potentially useful for monitoring and control of US ablation. To investigate these relationships, US ablation experiments were performed with simultaneous measurements of acoustic emissions, tissue echogenicity and tissue temperature on fresh bovine liver. Ex vivo tissue was exposed to 0.9-3.3-s bursts of unfocused, continuous-wave, 3.10-MHz US from a miniaturized 32-element array, which performed B-scan imaging with the same piezoelectric elements during brief quiescent periods. Exposures used pressure amplitudes of 0.8-1.4 MPa for exposure times of 6-20 min, sufficient to achieve significant thermal coagulation in all cases. Acoustic emissions received by a 1-MHz, unfocused passive cavitation detector, beamformed A-line signals acquired by the array, and tissue temperature detected by a needle thermocouple were sampled 0.3-1.1 times per second. Tissue echogenicity was quantified by the backscattered echo energy from a fixed region-of-interest within the treated zone. Acoustic emission levels were quantified from the spectra of signals measured by the passive cavitation detector, including subharmonic signal components at 1.55 MHz, broadband signal components within the band 0.3-1.1 MHz and low-frequency components within the band 10-30 kHz. Tissue ablation rates, defined as the thermally ablated volumes per unit time, were assessed by quantitative analysis of digitally imaged, macroscopic tissue sections. Correlation analysis was performed among the averaged and time-dependent acoustic emissions in each band considered, B-mode tissue echogenicity, tissue temperature and ablation rate. Ablation rate correlated significantly with broadband and low-frequency emissions, but was uncorrelated with subharmonic emissions. Subharmonic emissions were found to depend strongly on temperature in a nonlinear manner, with significant emissions occurring within different temperature ranges for each sonication amplitude. These results suggest potential roles for passive detection of acoustic emissions in guidance and control of bulk US ablation treatments.

Regurgitation quantification using 3D PISA in volume echocardiography

We present the first system for measurement of proximal isovelocity surface area (PISA) on a 3D ultrasound acquisition using modified ultrasound hardware, volumetric image segmentation and a simple efficient workflow. Accurate measurement of the PISA in 3D flow through a valve is an emerging method for quantitatively assessing cardiac valve regurgitation and function. Current state of the art protocols for assessing regurgitant flow require laborious and time consuming user interaction with the data, where a precise execution is crucial for an accurate diagnosis. We propose a new improved 3D PISA workflow that is initialized interactively with two points, followed by fully automatic segmentation of the valve annulus and isovelocity surface area computation. Our system is first validated against several in vitro phantoms to verify the calculations of surface area, orifice area and regurgitant flow. Finally, we use our system to compare orifice area calculations obtained from in vivo patient imaging measurements to an independent measurement and then use our system to successfully classify patients into mild-moderate regurgitation and moderate-severe regurgitation categories.

Toward Multiple Catheters Detection in Fluoroscopic Image Guided Interventions

Catheters are routinely inserted via vessels to cavities of the heart during fluoroscopic image guided interventions for electrophysiology (EP) procedures such as ablation. During such interventions, the catheter undergoes nonrigid deformation due to physician interaction, patients breathing, and cardiac motions. EP clinical applications can benefit from fast and accurate automatic catheter tracking in the fluoroscopic images. The typical low quality in fluoroscopic images and the presence of other medical instruments in the scene make the automatic detection and tracking of catheters in clinical environments very challenging. Toward the development of such an application, a robust and efficient method for detecting and tracking the catheter sheath is developed. The proposed approach exploits the clinical setup knowledge to constrain the search space while boosting both tracking speed and accuracy, and is based on a computationally efficient framework to trace the sheath and simultaneously detect one or multiple catheter tips. The algorithm is based on a modification of the fast marching weighted distance computation that efficiently calculates, on the fly, important geodesic properties in relevant regions of the image. This is followed by a cascade classifier for detecting the catheter tips. The proposed technique is validated on 1107 fluoroscopic images acquired on multiple patients across four different clinics, achieving multiple catheter tracking at a rate of 10 images/s with a very low false positive rate of 1.06.

Automated Quantification of Mitral Regurgitation by Three Dimensional Real Time Full Volume Color Doppler Transthoracic Echocardiography: A Validation with Cardiac Magnetic Resonance Imaging and Comparison with Two Dimensional Quantitative Methods

Background Accurate assessment of mitral regurgitation (MR) severity is crucial for clinical decision-making and optimizing patient outcomes. Recent advances in real-time three dimensional (3D) echocardiography provide the option of real-time full volume color Doppler echocardiography (FVCD) measurements. This makes it practical to quantify MR by subtracting aortic stroke volume from the volume of mitral inflow in an automated manner. Methods Thirty-two patients with more than a moderate degree of MR assessed by transthoracic echocardiography (TTE) were consecutively enrolled during this study. MR volume was measured by 1) two dimensional (2D) Doppler TTE, using the proximal isovelocity surface area (PISA) and the volumetric quantification methods (VM). Then, 2) real time 3D-FVCD was subsequently obtained, and dedicated software was used to quantify the MR volume. MR volume was also measured using 3) phase contrast cardiac magnetic resonance imaging (PC-CMR). In each patient, all these measurements were obtained within the same day. Automated MR quantification was feasible in 30 of 32 patients. Results The mean regurgitant volume quantified by 2D-PISA, 2D-VM, 3D-FVCD, and PC-CMR was 72.1 ± 27.7, 79.9 ± 36.9, 69.9 ± 31.5, and 64.2 ± 30.7 mL, respectively (p = 0.304). There was an excellent correlation between the MR volume measured by PC-CMR and 3D-FVCD (r = 0.85, 95% CI 0.70-0.93, p < 0.001). Compared with PC-CMR, Bland-Altman analysis for 3D-FVCD showed a good agreement (2 standard deviations: 34.3 mL) than did 2D-PISA or 2D-VM (60.0 and 62.8 mL, respectively). Conclusion Automated quantification of MR with 3D-FVCD is feasible and accurate. It is a promising tool for the real-time 3D echocardiographic assessment of patients with MR.

Recent advances in an artificial neural system for structural health monitoring

This paper discusses recent advances in modeling and simulation of an artificial neural system and simulation of wave propagation for designing structural health monitoring systems. An artificial neural system was modeled using piezoceramic nerves and electronic components. Wave propagation in a panel is modeled using classical plate theory and a closed-form solution of wave propagation and reflection is obtained. Equations representing a half sine input similar to a projectile impact or a tone burst excitation were added to the existing algorithm that predicts the response of the artificial neural system due to impulse inputs. Firing switches have been modeled in the simulation to predict the sequential firing of the neurons as the waves pass over them. Also, new active fiber sensors have been designed for use in the artificial neural system. Simulated responses of the artificial neural system are shown in this paper and indicate that large neural systems can be formed with hundreds of sensor nodes. Experiments were performed to study a small neural system on a glass fiber panel. Waves were induced in the panel due to a lead break to simulate a crack and due to an impact from an impact hammer. Testing showed the location of a crack could be determined within the unit cell of the neural system for an orthotropic panel.

Monitoring and simulating stable cavitation during ultrasound‐enhanced thrombolysis

The presence of stable cavitation has been shown to be highly correlated with thrombolytic efficacy for recombinant tissue plasminogen activator (rt‐PA) mediated thrombolysis. A commercial contrast agent, Definity, was used with 120 kHz pulsed ultrasound to nucleate, promote, and sustain stable cavitation. The effect of stable cavitation on increased penetration of rt‐PA into the clots is discussed. Also, the possibility of lowering the rt‐PA dose using sustained stable cavitation adjuvant to thrombolytics is presented. To understand the bubble dynamics involved, the bubble response was studied using the Keller‐Miksis model and stable and inertial cavitation thresholds were studied as a function of bubble radius. The largest mass loss (26.2%) was observed for clots treated with 120 kHz ultrasound (0.32 MPa peak‐to‐peak pressure amplitude, 80% duty cycle), rt‐PA (96 μg/ml) and stable cavitation nucleated by Definity. A comparable mass loss of 22% was observed at a much lower concentration of 11 μg/ml in th...