Dalong Liu

Real-Time 2-D Temperature Imaging Using Ultrasound

We have previously introduced methods for noninvasive estimation of temperature change using diagnostic ultrasound. The basic principle was validated both in vitro and in vivo by several groups worldwide. Some limitations remain, however, that have prevented these methods from being adopted in monitoring and guidance of minimally invasive thermal therapies, e.g., RF ablation and high-intensity-focused ultrasound (HIFU). In this letter, we present first results from a real-time system for 2-D imaging of temperature change using pulse-echo ultrasound. The front end of the system is a commercially available scanner equipped with a research interface, which allows the control of imaging sequence and access to the RF data in real time. A high-frame-rate 2-D RF acquisition mode, M2D, is used to capture the transients of tissue motion/deformations in response to pulsed HIFU. The M2D RF data is streamlined to the back end of the system, where a 2-D temperature imaging algorithm based on speckle tracking is implemented on a graphics processing unit. The real-time images of temperature change are computed on the same spatial and temporal grid of the M2D RF data, i.e., no decimation. Verification of the algorithm was performed by monitoring localized HIFU-induced heating of a tissue-mimicking elastography phantom. These results clearly demonstrate the repeatability and sensitivity of the algorithm. Furthermore, we present in vitro results demonstrating the possible use of this algorithm for imaging changes in tissue parameters due to HIFU-induced lesions. These results clearly demonstrate the value of the real-time data streaming and processing in monitoring, and guidance of minimally invasive thermotherapy.

Viscoelastic property measurement in thin tissue constructs using ultrasound

A variety of imaging methods employing the principle of acoustic radiation force (ARF) have been proposed recently. It is now well accepted that ARF-based methods produce significant improvement in contrast compared to coventional ultrasound. However, interpretation of the ARF-induced displacements is rendered difficult in the presence of nearby boundary conditions, e.g. skin imaging. We present a dual-element ultrasound transducer system for generating and tracking of localized tissue displacements in thin tissue constructs on hard substrates. The system is comprised of a highly focused 5-MHz ARF transducer and a confocal 25-MHz PVDF imaging transducer. The ARF transducer produces a sharp focus with 200 mum diameter and 1 mm depth of field. This allows for the generation of measurable displacements in tissue samples on hard substrates with thickness values down to 500 mum. The ARF transducer is driven by an arbitrary waveform generator for modulating the 5-MHZ ARF carrier. Impulse-like and longer duration sine- modulated ARF pulses are possible with intermittent M-mode data acquisition for displacement tracking. Spatio-temporal maps of tissue displacements in response to a variety of modulated ARF beams are produced in tissue-mimicking elastography phantoms on a hard substrate. The frequency response was measured for phantoms with different stiffness and thickness values. The frequency response exhibits resonant behavior determined by the stiffness and the thickness of the samples. We have also used the extended Kalman filter (EKF) for tracking the apparent stiffness and viscosity of samples subjected to sinusoidaly-modulated ARF. Finally, C-mode imaging results of a soft phantom with a harder inclusion are shown to demonstrate the potential for significant contrast enhancement with ARF-based methods.

Real-Time Implementation of a Dual-Mode Ultrasound Array System: In Vivo Results

A real-time dual-mode ultrasound array (DMUA) system for imaging and therapy is described. The system utilizes a concave (40-mm radius of curvature) 3.5 MHz, 32 element array, and modular multichannel transmitter/receiver. The system is capable of operating in a variety of imaging and therapy modes (on transmit) and continuous receive on all array elements even during high-power operation. A signal chain consisting of field-programmable gate arrays and graphical processing units is used to enable real time, software-defined beamforming and image formation. Imaging data, from quality assurance phantoms as well as in vivo small- and large-animal models, are presented and discussed. Corresponding images obtained using a temporally-synchronized and spatially-aligned diagnostic probe confirm the DMUAs ability to form anatomically-correct images with sufficient contrast in an extended field of view around its geometric center. In addition, high-frame rate DMUA data also demonstrate the feasibility of detection and localization of echo changes indicative of cavitation and/or tissue boiling during high-intensity focused ultrasound exposures with 45-50 dB dynamic range. The results also show that the axial and lateral resolution of the DMUA are consistent with its fnumber and bandwidth with well-behaved speckle cell characteristics. These results point the way to a theranostic DMUA system capable of quantitative imaging of tissue property changes with high specificity to lesion formation using focused ultrasound.

Realtime Control of Multiple-focus Phased Array Heating Patterns Based on Noninvasive Ultrasound Thermography

A system for the realtime generation and control of multiple-focus ultrasound phased-array heating patterns is presented. The system employs a 1-MHz, 64-element array and driving electronics capable of fine spatial and temporal control of the heating pattern. The driver is integrated with a realtime 2-D temperature imaging system implemented on a commercial scanner. The coordinates of the temperature control points are defined on B-mode guidance images from the scanner, together with the temperature set points and controller parameters. The temperature at each point is controlled by an independent proportional, integral, and derivative controller that determines the focal intensity at that point. Optimal multiple-focus synthesis is applied to generate the desired heating pattern at the control points. The controller dynamically reallocates the power available among the foci from the shared power supply upon reaching the desired temperature at each control point. Furthermore, anti-windup compensation is implemented at each control point to improve the system dynamics. In vitro experiments in tissue-mimicking phantom demonstrate the robustness of the controllers for short (2-5 s) and longer multiple-focus high-intensity focused ultrasound exposures. Thermocouple measurements in the vicinity of the control points confirm the dynamics of the temperature variations obtained through noninvasive feedback.

Modified autocorrelation method compared with maximum entropy method and RF cross correlation method as mean frequency estimator for Doppler ultrasound

The modified autocorrelation method (MAC) incorporating two-dimensional temporal and spatial averaging for mean frequency estimation in ultrasound color/flow mapping is evaluated. The equivalence among the MA, the classic autocorrelation method (AC) and the RF cross-correlation method has been investigated. Recently, the maximum entropy method (MEM) has been applied to the ultrasound color flow imaging. The performance of the MA, AC, and the MEM methods is examined using computer simulations. Simulation results show that the MA method performs best in all of the cases especially for short and highly noisy signals. The MEM performs similarly with that of the original AC method in most cases but shows more accurate results than the AC method for short and extremely noisy signals.<<ETX>>

Feasibility of Targeting Atherosclerotic Plaques by High-Intensity–focused Ultrasound: An In Vivo Study

PURPOSE To investigate the feasibility and acute safety of targeting atherosclerotic plaques by high-intensity-focused ultrasound (US) in vivo through a noninvasive extracorporeal approach. MATERIALS AND METHODS Four swine were included in this prospective study, three of which were familial hypercholesterolemic swine. The procedure was done under general anesthesia. After US identification of atherosclerotic plaques within the femoral arteries, plaques were targeted by high-intensity focused US with an integrated dual-mode US array system. Different ablation protocols were used to meet the study objectives, and animals were then euthanized at different time points. Targeted arterial segments were stained by hematoxylin and eosin for histopathologic examination. Numeric values are presented as means ± standard deviation. RESULTS All swine tolerated the procedure well, with no arterial dissection, perforation, or rupture. Discrete lesions were detected in the first two swine, measuring 0.54 mm ± 0.10 and 0.25 mm ± 0.03 in cross-sectional dimensions in the first and 0.50 mm ± 0.12 and 0.24 mm ± 0.15 in the second. Confluent ablation zones were identified in the last two swine, measuring 6.92 mm and 0.93 mm in the third and 2.97 mm and 2.52 mm in the fourth. Lesions showed necrotic cores and peripheral reactive inflammatory infiltration. The endothelium overlying targeted arterial segments remained intact. CONCLUSIONS The results demonstrate the feasibility and acute safety of targeting atherosclerotic plaques by high-intensity-focused US in vivo. Further long-term studies are needed to assess how induction of these lesions can modify the progression of atherosclerotic plaques.

Imaging vascular mechanics using ultrasound: Phantom and in vivo results

We introduce a new method for simultaneous imaging of tissue motion and flow with subsample accuracy in both axial and lateral directions. The method utilizes a phase-coupled 2D speckle tracking approach, which employs the true 2D complex cross correlation to find subpixel displacements in both axial and lateral directions. We have also modified the imaging sequence on a Sonix RP scanner to allow high frame rate 2D data collection in a limited field of view covering the region of interest (M2D-mode). Together with the robust 2D speckle tracking method, M2D imaging allows for capturing the full dynamics of the flow and wall/tissue motion, even when the flow is primarily in the lateral direction (with respect to the imaging beam). The fine vector displacement estimates in both axial and lateral directions are shown to allow for smooth and contiguous strain and shear strain calculations with minimal filtering. The quality of the displacement and strain fields is demonstrated by experimental results from a flow phantom (ATS Model 524) and in vivo images of the carotid artery in a healthy volunteer. The results clearly demonstrate the feasibility of simultaneous imaging of the vector flow field and the wall/tissue motion and the corresponding strains at high spatial and temporal sampling. This may provide an essential tool in modeling the fluid-solid interactions between the blood and blood vessel, a key challenge in vascular biomechanics.

Real-time monitoring of thermal and mechanical response to sub-therapeutic HIFU beams in vivo

We present first in vivo results of realtime 2D imaging of thermal and mechanical response to sub-therapeutic HIFU beams in a small-animal tumor model. A 2.5 MHz focused transducer with fnumber = 1.05 was used to generate short (≈ 1.5 sec) exposure in LNCap tumors implanted in the hindlimb of nude mice with power levels suitable to produce 4–6 °C rise in tissue (based on results in thermally-calibrated tissue mimicking phantoms). Beamformed RF data was collected at 99 frames per second to allow for capturing tissue displacements due to both temperature and breathing cycles. To ascertain the systems capability to cover an adequate range of periodic tissue motion, the sub-therapeutic HIFU beams were sinusoidally modulated at frequencies higher than the pulsatory frequency in the mouse model. Results from our previously published 2D temperature imaging algorithm demonstrate the capture of strains due to temperature change, pulsatory motions near arteries, and sinusoidal oscillations due to acoustic radiation force effects due to the HIFU-beam modulation. To reduce the effects of mechanical strains due to motion and ARF modulation, an iterative image reconstruction algorithm was used. The method employs alternating projections that employ the non-negativity constraints (TΔ(r, t) ≥ 0) and a multi-dimensional time-varying Gaussian filter derived from the spatio-temporal impulse response of the transient bioheat transfer equation (tBHTE) in each iteration. This method of projection onto convex sets (POCS) allows for the removal of artifacts inconsistent with the temperature evolution model in tissue media while preserving real temperature data until convergence is achieved. Our in vivo results show that the POCS algorithm achieves significant reduction in the temperature artifacts due to breathing and pulsations while preserving true temperature profiles with excellent spatial and temporal resolution. These results clearly demonstrate the sensitivity and specificity of ultrasound thermography to the spatially-confined sub-therapeutic HIFU beams. This performance is unmatched by other noninvasive methods for imaging temperature.

In Vivo application and localization of transcranial focused ultrasound using dual-mode ultrasound arrays

Focused ultrasound (FUS) has been proposed for a variety of transcranial applications, including neuromodulation, tumor ablation, and blood-brain barrier opening. A flurry of activity in recent years has generated encouraging results demonstrating its feasibility in these and other applications. To date, monitoring of FUS beams has been primarily accomplished using MR guidance, where both MR thermography and elastography have been used. The recent introduction of real-time dual-mode ultrasound array (DMUA) systems offers a new paradigm in transcranial focusing. In this paper, we present first experimental results of ultrasound-guided transcranial FUS (tFUS) application in a rodent brain, both ex vivo and in vivo. DMUA imaging is used for visualization of the treatment region for placement of the focal spot within the brain. This includes the detection and localization of pulsating blood vessels at or near the target point(s). In addition, DMUA imaging is used to monitor and localize the FUS-tissue interactions in real time. In particular, a concave (40 mm radius of curvature), 32-element, 3.5-MHz DMUA prototype was used for imaging and tFUS application in ex vivo and in vivo rat models. The ex vivo experiments were used to evaluate the point spread function of the transcranial DMUA imaging at various points within the brain. In addition, DMUA-based transcranial ultrasound thermography measurements were compared with thermocouple measurements of subtherapeutic tFUS heating in rat brain ex vivo. The ex vivo setting was also used to demonstrate the capability of DMUA to produce localized thermal lesions. The in vivo experiments were designed to demonstrate the ability of the DMUA to apply, monitor, and localize subtherapeutic tFUS patterns that could be beneficial in transient blood-brain barrier opening. The results show that although the DMUA focus is degraded due to the propagation through the skull, it still produces localized heating effects within a sub-millimeter volume. In addition, DMUA transcranial echo data from brain tissue allow for reliable estimation of temperature change.

Real-time two-dimensional temperature imaging using ultrasound

We present a system for real-time 2D imaging of temperature change in tissue media using pulse-echo ultrasound. The frontend of the system is a SonixRP ultrasound scanner with a research interface giving us the capability of controlling the beam sequence and accessing radio frequency (RF) data in real-time. The beamformed RF data is streamlined to the backend of the system, where the data is processed using a two-dimensional temperature estimation algorithm running in the graphics processing unit (GPU). The estimated temperature is displayed in real-time providing feedback that can be used for real-time control of the heating source. Currently we have verified our system with elastography tissue mimicking phantom and in vitro porcine heart tissue, excellent repeatability and sensitivity were demonstrated.