Subharmonic,Non-linear Fundamental and Ultraharmonic Imaging of Microbubble Contrast at High Frequencies

There is increasing use of ultrasound contrast agent in high-frequency ultrasound imaging. However, conventional contrast detection methods perform poorly at high frequencies. We performed systematic in vitro comparisons of subharmonic, non-linear fundamental and ultraharmonic imaging for different depths and ultrasound contrast agent concentrations (Vevo 2100 system with MS250 probe and MicroMarker ultrasound contrast agent, VisualSonics, Toronto, ON, Canada). We investigated 4-, 6- and 10-cycle bursts at three power levels with the following pulse sequences: B-mode, amplitude modulation, pulse inversion and combined pulse inversion/amplitude modulation. The contrast-to-tissue (CTR) and contrast-to-artifact (CAR) ratios were calculated. At a depth of 8 mm, subharmonic pulse-inversion imaging performed the best (CTR = 26 dB, CAR = 18 dB) and at 16 mm, non-linear amplitude modulation imaging was the best contrast imaging method (CTR = 10 dB). Ultraharmonic imaging did not result in acceptable CTRs and CARs. The best candidates from the in vitro study were tested in vivo in chicken embryo and mouse models, and the results were in a good agreement with the in vitro findings.     

Real-time texture analysis for identifying optimum microbubble concentration in 2-D ultrasonic particle image velocimetry

Many recent studies on ultrasonic particle image velocimetry (Echo PIV) showed that the accuracy of two-dimensional (2-D) flow velocity measured depends largely on the concentration of ultrasound contrast agents (UCAs) during imaging. This article presents a texture-based method for identifying the optimum microbubble concentration for Echo PIV measurements in real-time. The texture features, standard deviation of gray level, and contrast, energy and homogeneity of gray level co-occurrence matrix were extracted from ultrasound contrast images of rotational and pulsatile flow (10 MHz) in vitro and in vivo mouse common carotid arterial flow (40 MHz) with UCAs at various concentrations. The results showed that, at concentration of 0.8∼2 × 10³ bubbles/mL in vitro and 1∼5 × 10⁵ bubbles/mL in vivo, image texture features had a peak value or trough value, and velocity vectors with high accuracy can be obtained. Otherwise, poor quality velocity vectors were obtained. When the texture features were used as a feature set, the accuracy of K-nearest neighbor classifier can reach 86.4% in vitro and 87.5% in vivo, respectively. The texture-based method is shown to be able to quickly identify the optimum microbubble concentration and improve the accuracy for Echo PIV imaging.     

Flow Velocity Mapping Using Contrast Enhanced High-Frame-Rate Plane Wave Ultrasound and Image Tracking: Methods and Initial in Vitro and in Vivo Evaluation

Ultrasound imaging is the most widely used method for visualising and quantifying blood flow in medical practice, but existing techniques have various limitations in terms of imaging sensitivity, field of view, flow angle dependence, and imaging depth. In this study, we developed an ultrasound imaging velocimetry approach capable of visualising and quantifying dynamic flow, by combining high-frame-rate plane wave ultrasound imaging, microbubble contrast agents, pulse inversion contrast imaging and speckle image tracking algorithms. The system was initially evaluated in vitro on both straight and carotid-mimicking vessels with steady and pulsatile flows and in vivo in the rabbit aorta. Colour and spectral Doppler measurements were also made. Initial flow mapping results were compared with theoretical prediction and reference Doppler measurements and indicate the potential of the new system as a highly sensitive, accurate, angle-independent and full field-of-view velocity mapping tool capable of tracking and quantifying fast and dynamic flows.     

Listening to the Cochlea With High-Frequency Ultrasound

We have developed a high-frequency pulsed-wave Doppler ultrasound probe as a promising minimally-invasive technique for measuring intracochlear mechanics without damaging the cochlea. Using a custom high-frequency ultrasound system, we have measured dynamic motion of intracochlear structures by recording the pulsed-wave Doppler signal resulting from the vibration of the basilar and round window membranes. A 45 MHz needle-mounted Doppler probe was fabricated and placed against the round window membranes of eight different fresh human temporal bones. Pulsed-wave ultrasonic Doppler measurements were performed on the basilar membrane and round window membrane during the application of pure tones to the external ear canal. Doppler vibrational information for acoustic input frequencies ranging from 100–2000 Hz was collected and normalized to the sound pressure in the ear canal. The middle ear resonance, located at approximately 1000 Hz, could be characterized from the membrane velocities, which agreed well with literature values. The maximum normalized mean velocity of the round window and the basilar membrane were 180 μm/s/Pa and 27 μm/s/Pa at 800 Hz. The mean phase difference between the membrane displacements and the applied ear canal sound pressure showed a flat response almost up to 500 Hz where it began to accumulate. This is the first study that reports the application of high frequency pulsed wave Doppler ultrasound for measuring the vibration of basilar membrane through the round window. Since it is not required to open or damage the cochlea, this technique might be applicable for investigating cochlear dynamics, in vivo.     

Detectability of Small Blood Vessels with High-Frequency Power Doppler and Selection of Wall Filter Cut-Off Velocity for Microvascular Imaging

Power Doppler imaging of physiologic and pathologic angiogenesis is widely used in preclinical studies to track normal development, disease progression and treatment efficacy but can be challenging given the presence of small blood vessels and slow flow velocities. Power Doppler images can be plagued with false-positive color pixels or undetected vessels, thereby complicating the interpretation of vascularity metrics such as color pixel density (CPD). As an initial step toward improved microvascular quantification, flow-phantom experiments were performed to establish relationships between vessel detection and various combinations of vessel size (160, 200, 250, 300 and 360 μm), flow velocity (4, 3, 2, 1 and 0.5 mm/s) and transducer frequency (30 and 40 MHz) while varying the wall filter cut-off velocity. Receiver operating characteristic (ROC) curves and areas under ROC curves indicate that good vessel detection performance can be achieved with a 40-MHz transducer for flow velocities ≥2 mm/s and with a 30-MHz transducer for flow velocities ≥1 mm/s. In the second part of the analysis, CPD was plotted as a function of wall filter cut-off velocity for each flow-phantom data set. Three distinct regions were observed: overestimation of CPD at low cut-offs, underestimation of CPD at high cut-offs and a plateau at intermediate cut-offs. The CPD at the plateau closely matched the phantom's vascular volume fraction and the length of the plateau corresponded with the flow-detection performance of the Doppler system assessed using ROC analysis. Color pixel density vs. wall filter cut-off curves from analogous in vivo experiments exhibited the same shape, including a distinct CPD plateau. The similar shape of the flow-phantom and in vivo curves suggests that the presence of a plateau in vivo can be used to identify the best-estimate CPD value that can be treated as a quantitative vascularity metric. The ability to identify the best CPD estimate is expected to improve quantification of angiogenesis and anti-vascular treatment responses with power Doppler. (E-mail: jlacefield@eng.uwo.ca)     

Optimizing Sensitivity of Ultrasound Contrast-Enhanced Super-Resolution Imaging by Tailoring Size Distribution of Microbubble Contrast Agent

Ultrasound contrast-enhanced super-resolution imaging has recently attracted attention because of its extraordinary ability to image vascular features much smaller than the ultrasound diffraction limit. This method requires sensitive detection of separable microbubble events despite a noisy tissue background to indicate the microvasculature, and any approach that could improve the sensitivity of the ultrasound system to individual microbubbles would be highly beneficial. In this study, we evaluated the effect of varying microbubble size on super-resolution imaging sensitivity. Microbubble preparations were size sorted into different mean diameters and then were imaged at equal concentrations. Commercially manufactured Definity and Optison were also imaged for comparison. Both in vitro experiments in phantom vessels and in vivo experiments imaging rat tumors revealed that the sensitivity of contrast-enhanced super-resolution imaging can be improved by using microbubbles with a larger diameter.     

In vivo Intravascular Ultrasound-guided Photoacoustic Imaging of Lipid in Plaques Using an Animal Model of Atherosclerosis

We present a preliminary study demonstrating the capability of ultrasound-guided intravascular photoacoustic (IVPA) imaging to visualize the depth-resolved distribution of lipid deposits in atherosclerotic plaques in vivo. Based on the characteristic optical absorption of lipid in the near infrared wavelength range, IVPA imaging at a single, 1720 nm, wavelength was used to provide a spatially-resolved, direct measurement of lipid content in atherosclerotic arteries. By overlaying an IVPA image with a spatially co-registered intravascular ultrasound (IVUS) image, the combined IVPA/IVUS image was used to visualize lipid distribution within the vessel wall. Ultrasound-guided IVPA imaging was performed in vivo in the abdominal aorta of a Watanabe heritable hyperlipidemic (WHHL) rabbit. Subsequently, the excised rabbit aorta filled with a solution of red blood cells (RBC) was then imaged ex vivo, and histology was obtained in the section adjacent to the imaged cross-section. To demonstrate the potential for future clinical application of IVPA/IVUS imaging, a sample of diseased human right coronary artery (RCA) was also imaged. Both in vivo and ex vivo IVPA images clearly showed the distribution of lipid in the atherosclerotic vessels. In vivo IVPA imaging was able to identify diffuse, lipid-rich plaques in the WHHL rabbit model of atherosclerosis. Furthermore, IVPA imaging at a single wavelength was able to identify the lipid core within the human RCA ex vivo. Our results demonstrate that ultrasound-guided IVPA imaging can identify lipid in atherosclerotic plaques in vivo. Importantly, the IVPA/IVUS images were obtained in presence of luminal blood and no saline flush or balloon occlusion was required. Overall, our studies suggest that ultrasound-guided IVPA imaging can potentially be used for depth-resolved visualization of lipid deposits within the anatomical context of the vessel wall and lumen. Therefore, IVUS/IVPA imaging may become an important tool for the detection of rupture-prone plaques.     

In Vivo Observation of the Hypo-echoic “Black Hole” Phenomenon in Rat Arterial Bloodstream: A Preliminary Study

The “black hole,” a hypo-echoic hole at the center of the bloodstream surrounded by a hyper-echoic zone in cross-sectional views, has been observed in ultrasound backscattering measurements of blood with red blood cell aggregation in in vitro studies. We investigated whether the phenomenon occurs in the in vivo arterial bloodstream of rats using a high-frequency ultrasound imaging system. Longitudinal and cross-sectional ultrasound images of the rat common carotid artery (CCA) and abdominal aorta were obtained using a 40-MHz ultrasound system. A high-frame-rate retrospective imaging mode was employed to precisely examine the dynamic changes in blood echogenicity in the arteries. When the imaging was performed with non-invasive scanning, blood echogenicity was very low in the CCA as compared with the surrounding tissues, exhibiting no hypo-echoic zone at the center of the vessel. Invasive imaging of the CCA by incising the skin and subcutaneous tissues at the imaging area provided clearer and brighter blood echo images, showing the “black hole” phenomenon near the center of the vessel in longitudinal view. The “black hole” was also observed in the abdominal aorta under direct imaging after laparotomy. The aortic “black hole” was clearly observed in both longitudinal and cross-sectional views. Although the “black hole” was always observed near the center of the arteries during the diastolic phase, it dissipated or was off-center along with the asymmetric arterial wall dilation at systole. In conclusion, we report the first in vivo observation of the hypo-echoic “black hole” caused by the radial variation of red blood cell aggregation in arterial bloodstream.     

Effects of Vascularity and Differentiation of Hepatocellular Carcinoma on Tumor and Liver Stiffness: In Vivo and in Vitro Studies

Tissue stiffness has been found to be a useful predictor of malignancy in various cancers. However, data on the stiffness of hepatocellular carcinomas (HCCs) and their background livers are contradictory. The aim of this study was to investigate the effects of vascularity and histologic differentiation on HCC stiffness. Elastography point quantification (ElastPQ), a new shear wave-based elastography method, was used to measure liver stiffness in vivo in 99 patients with pathology-proven HCC. Lesion vascularity was assessed using contrast-enhanced ultrasound, computed tomography and/or magnetic resonance imaging. The association of HCC vascularity and differentiation with liver stiffness was determined. In addition, in vitro stiffness of 20 of the 99 surgical HCC specimens was mechanically measured and compared with in vivo measurements. We found that in vivo stiffness was significantly higher than in vitro stiffness in both HCCs and their background livers (p < 0.0001). Moreover, significantly higher stiffness was observed in hyper-vascular and poorly differentiated lesions than in hypo-vascular (p = 0.0352) and moderately to well-differentiated lesions (p = 0.0139). These in vivo and in vitro studies reveal that shear wave-based ultrasound elasticity quantification can effectively measure in vivo liver stiffness.     

Shunt Flow Evaluation in Congenital Heart Disease Based on Two-Dimensional Speckle Tracking

High-frame-rate ultrasound speckle tracking was used for quantification of peak velocity in shunt flows resulting from septal defects in congenital heart disease. In a duplex acquisition scheme implemented on a research scanner, unfocused transmit beams and full parallel receive beamforming were used to achieve a frame rate of 107 frames/s for full field-of-view flow images with high accuracy, while also ensuring high-quality focused B-mode tissue imaging. The setup was evaluated in vivo for neonates with atrial and ventricular septal defects. The shunt position was automatically tracked in B-mode images and further used in blood speckle tracking to obtain calibrated shunt flow velocities throughout the cardiac cycle. Validation toward color flow imaging and pulsed wave Doppler with manual angle correction indicated that blood speckle tracking could provide accurate estimates of shunt flow velocities. The approach was less biased by clutter filtering compared with color flow imaging and was able to provide velocity estimates beyond the Nyquist range. Possible placements of sample volumes (and angle corrections) for conventional Doppler resulted in a peak shunt velocity variations of 0.49–0.56 m/s for the ventricular septal defect of patient 1 and 0.38–0.58 m/s for the atrial septal defect of patient 2. In comparison, the peak velocities found from speckle tracking were 0.77 and 0.33 m/s for patients 1 and 2, respectively. Results indicated that complex intraventricular flow velocity patterns could be quantified using high-frame-rate speckle tracking of both blood and tissue movement. This could potentially help increase diagnostic accuracy and decrease inter-observer variability when measuring peak velocity in shunt flows.     

Localized in Vivo Model Drug Delivery with Intravascular Ultrasound and Microbubbles

An intravascular ultrasound (IVUS) and microbubble drug delivery system was evaluated in both ex vivo and in vivo swine vessel models. Microbubbles with the fluorophore DiI embedded in the shell as a model drug were infused into ex vivo swine arteries at a physiologic flow rate (105 mL/min) while a 5-MHz IVUS transducer applied ultrasound. Ultrasound pulse sequences consisted of acoustic radiation force pulses to displace DiI-loaded microbubbles from the vessel lumen to the wall, followed by higher-intensity delivery pulses to release DiI into the vessel wall. Insonation with both the acoustic radiation force pulse and the delivery pulse increased DiI deposition 10-fold compared with deposition with the delivery pulse alone. Localized delivery of DiI was then demonstrated in an in vivo swine model. The theoretical transducer beam width predicted the measured angular extent of delivery to within 11%. These results indicate that low-frequency IVUS catheters are a viable method for achieving localized drug delivery with microbubbles.     

Imaging Microvasculature with Contrast-Enhanced Ultraharmonic Ultrasound

Atherosclerotic plaque neovascularization was shown to be one of the strongest predictors of future cardiovascular events. Yet, the clinical tools for coronary wall microvasculature detection in vivo are lacking. Here we report an ultrasound pulse sequence capable of detecting microvasculature invisible in conventional intracoronary imaging. The method combines intravascular ultrasound with an ultrasound contrast agent, i.e., a suspension of microscopic vascular acoustic resonators that are small enough to penetrate the capillary bed after intravenous administration. The pulse sequence relies on brief chirp excitations to extract ultraharmonic echoes specific to the ultrasound contrast agent. We implemented the pulse sequence on an intravascular ultrasound probe and successfully imaged the microvasculature of a 6 days old chicken embryo respiratory organ. The feasibility of microvasculature imaging with intravascular ultrasound sets the stage for a translation of the method to studies of intra-plaque neovascularization detection in humans.     

In Vivo High-Frequency Ultrasound for the Characterization of Thrombi Associated with Aortic Aneurysms in an Experimental Mouse Model

The development of abdominal aortic aneurysm (AAA) associated thrombi plays an important role during the onset and progression of AAAs. The aim of this study was to evaluate the potential of high-frequency ultrasound for characterization of AAA associated thrombi in an apolipoprotein-E-deficient mouse-model. Ultrasound measurements were performed using a high-resolution ultrasound system (Vevo770, FUJIFILM VisualSonics, Inc., Toronto, ON, Canada) with a 30?MHz linear-array transducer (RMV707 B). Magnetic resonance imaging with a 3 Tesla scanner (Achieva MR system, Philips Healthcare, Best, The Netherlands) and a single-loop microscopy coil was performed as a reference standard. All stages of aneurysm development were evaluated by histologic analyses. The “signal-thrombus-matrix” to “signal-blood” ratio on high-frequency ultrasound measurements showed a strong correlation (R²?=?0.81, p?<0.05) with the state of extracellular matrix remodeling. Furthermore, size measurements derived from the high-frequency ultrasound correlated well with magnetic resonance imaging and histology. This study demonstrated that high-frequency ultrasound enables the reliable in vivo quantification of extracellular matrix remodeling at various stages of thrombus development, based on the thrombus echogenicity.     

In vivo Doppler Ultrasound Quantification of Turbulence Intensity Using A High-Pass Frequency Filter Method

The objective of this investigation was to implement a high-pass frequency filter method to analyze Doppler ultrasound velocity waveforms and quantify turbulence intensity (TI) in vivo. Doppler velocity data were analyzed using two techniques, based on either ensemble averaging or high-pass frequency domain filtering of the periodic waveforms. The accuracy and precision of TI measurements were determined with controlled in vitro experiments, using a pulsatile-flow model of a stenosed carotid bifurcation. The high-pass filter technique was also applied in vivo to determine whether this technique could successfully distinguish between pertinent hemodynamic sites within the carotid artery bifurcation. Twenty-five seconds of Doppler audio data were acquired at three sites (common carotid artery [CCA], internal carotid artery [ICA] stenosis and distal ICA) within 10 human carotid arteries, and repeated three times. Doppler velocity data were analyzed using a ninth-order high-pass Butterworth filter with a 12-Hz inflection point. TI measured within the CCA and distal ICA was found to be significantly different (p < 0.0001) for moderate to nearly occluded carotid artery classifications. Also, TI measured within the distal ICA increased with stenosis severity, with the ability to distinguish between each stenosis class (p < 0.05). This investigation demonstrated the ability to precisely quantify TI using a conventional Doppler ultrasound machine in human subjects, without interfering with normal clinical protocols. (E-mail: david.holdsworth@imaging.robarts.ca)     

Multichannel Pulsed Doppler Signal Processing for Vascular Measurements in Mice

The small size, high heart rate and small tissue displacement of a mouse require small sensors that are capable of high spatial and temporal tissue displacement resolutions and multichannel data acquisition systems with high sampling rates for simultaneous measurement of high fidelity signals. We developed and evaluated an ultrasound-based mouse vascular research system (MVRS) that can be used to characterize vascular physiology in normal, transgenic, surgically altered and disease models of mice. The system consists of multiple 10/20 MHz ultrasound transducers, analog electronics for Doppler displacement and velocity measurement, signal acquisition and processing electronics and personal computer based software for real-time and off-line analysis. In vitro testing of the system showed that it is capable of measuring tissue displacement as low as 0.1 μm and tissue velocity (μm/s) starting from 0. The system can measure blood velocities up to 9 m/s (with 10 MHz Doppler at a PRF of 125 kHz) and has a temporal resolution of 0.1 milliseconds. Ex vivo tracking of an excised mouse carotid artery wall using our Doppler technique and a video pixel tracking technique showed high correlation (R² = 0.99). The system can be used to measure diameter changes, augmentation index, impedance spectra, pulse wave velocity, characteristic impedance, forward and backward waves, reflection coefficients, coronary flow reserve and cardiac motion in murine models. The system will facilitate the study of mouse vascular mechanics and arterial abnormalities resulting in significant impact on the evaluation and screening of vascular disease in mice. (E-mail: areddy@bcm.edu)     

High Spatial and Temporal Resolution Observations of Pulsatile Changes in Blood Echogenicity in the Common Carotid Artery of Rats

Previous studies have found that ultrasound backscatter from blood in vascular flow systems varies under pulsatile flow, with the maximum values occurring during the systolic period. This phenomenon is of particular interest in hemorheology because it is contrary to the well-known fact that red blood cell (RBC) aggregation, which determines the intensity of ultrasound backscatter from blood, decreases at a high systolic shear rate. In the present study, a rat model was used to provide basic information on the characteristics of blood echogenicity in arterial blood flow to investigate the phenomenon of RBC aggregation under pulsatile flow. Blood echogenicity in the common carotid arteries of rats was measured using a high-frequency ultrasound imaging system with a 40-MHz probe. The electrocardiography-based kilohertz visualization reconstruction technique was employed to obtain high-temporal-resolution and high-spatial-resolution time-course B-mode cross-sectional and longitudinal images of the vessel. The experimental results indicate that blood echogenicity in rat carotid arteries varies during a cardiac cycle. Blood echogenicity tends to decrease during early systole and reaches its peak during late systole, followed by a slow decline thereafter. The time delay of the echogenicity peak from peak systole in the present results is the main difference from previous in vitro and in vivo observations of backscattering peaks during early systole, which may be caused by the very rapid heart rates and low RBC aggregation tendency of rats compared with humans and other mammalian species. The present study may provide useful information elucidating the characteristics of RBC aggregation in arterial blood flow.     

High-Intensity Focused Ultrasound Sonothrombolysis: The Use of Perfluorocarbon Droplets to Achieve Clot Lysis at Reduced Acoustic Power

The purpose of this study was to evaluate use of intravascular perfluorocarbon droplets to reduce the sonication power required to achieve clot lysis with high-intensity focused ultrasound. High-intensity focused ultrasound with droplets was initially applied to blood clots in an in vitro flow apparatus, and inertial cavitation thresholds were determined. An embolic model for ischemic stroke was used to illustrate the feasibility of this technique in vivo. Recanalization with intravascular droplets was achieved in vivo at 24 ± 5% of the sonication power without droplets. Recanalization occurred in 71% of rabbits that received 1-ms pulsed sonications during continuous intravascular droplet infusion (p = 0.041 vs controls). Preliminary experiments indicated that damage was confined to the ultrasonic focus, suggesting that tolerable treatments would be possible with a more tightly focused hemispheric array that allows the whole focus to be placed inside of the main arteries in the human brain.     

In Vivo Thermal Ablation Monitoring Using Ultrasound Echo Decorrelation Imaging

Previous work indicated that ultrasound echo decorrelation imaging can track and quantify changes in echo signals to predict thermal damage during in vitro radiofrequency ablation (RFA). In the in vivo studies reported here, the feasibility of using echo decorrelation imaging as a treatment monitoring tool was assessed. RFA was performed on normal swine liver (N = 5), and ultrasound ablation using image-ablate arrays was performed on rabbit liver implanted with VX2 tumors (N = 2). Echo decorrelation and integrated backscatter were computed from Hilbert transformed pulse-echo data acquired during RFA and ultrasound ablation treatments. Receiver operating characteristic (ROC) curves were employed to assess the ability of echo decorrelation imaging and integrated backscatter to predict ablation. Area under the ROC curves (AUROC) was determined for RFA and ultrasound ablation using echo decorrelation imaging. Ablation was predicted more accurately using echo decorrelation imaging (AUROC = 0.832 and 0.776 for RFA and ultrasound ablation, respectively) than using integrated backscatter (AUROC = 0.734 and 0.494).     

Improved objective selection of power Doppler wall-filter cut-off velocity for accurate vascular quantification

The wall-filter selection curve method is proposed to objectively identify a cut-off velocity that minimizes artifacts in power Doppler images. A selection curve, which is constructed by plotting the color pixel density (CPD) as a function of the cut-off velocity, exhibits characteristic intervals hypothesized to include the optimum cut-off velocity. This article presents an improved implementation of the method that automatically detects characteristic intervals in a selection curve and selects an operating point cut-off velocity along a characteristic interval. The method is applied to subregions within the Doppler image to adapt the cut-off velocity to local variations in vascularity. The method's performance is evaluated in 30-MHz power Doppler images of a four-vessel flow phantom. At high (>5 mm/s) flow velocities, qualitative improvements in vessel delineation are achieved and the CPD in the resulting images is accurate to within 3% of the vascular volume fraction of the phantom.     

Dual-mode IVUS transducer for image-guided brain therapy: preliminary experiments

In this study, we investigated the feasibility of using 3.5-Fr intravascular ultrasound (IVUS) catheters for minimally-invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated by: (1) retro-fitting a commercial 3.5-Fr IVUS catheter with a 5 × 0.5 × 0.22 mm PZT-4 transducer for 9-MHz imaging and (2) testing an identical transducer for therapy potential with 3.3-MHz continuous-wave excitation. The imaging transducer was compared with a 9-Fr, 9-MHz ICE catheter when visualizing the post-mortem ovine brain and was also used to attempt vascular access to an in vivo porcine brain. A net average electrical power input of 700 mW was applied to the therapy transducer, producing a temperature rise of +13.5°C at a depth of 1.5 mm in live brain tumor tissue in the mouse model. These results suggest that it may be feasible to combine the imaging and therapeutic capabilities into a single device as a clinically-viable instrument.