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1.  SIMULTANEOUS BILATERAL REAL-TIME 3-D TRANSCRANIAL ULTRASOUND IMAGING AT 1 MHZ THROUGH POOR ACOUSTIC WINDOWS 
Ultrasound in medicine & biology  2013;39(4):721-734.
Ultrasound imaging has been proposed as a rapid, portable alternative imaging modality to examine stroke patients in pre-hospital or emergency room settings. However, in performing transcranial ultrasound examinations, 8%–29% of patients in a general population may present with window failure, in which case it is not possible to acquire clinically useful sonographic information through the temporal bone acoustic window. In this work, we describe the technical considerations, design and fabrication of low-frequency (1.2 MHz), large aperture (25.3 mm) sparse matrix array transducers for 3-D imaging in the event of window failure. These transducers are integrated into a system for real-time 3-D bilateral transcranial imaging—the ultrasound brain helmet—and color flow imaging capabilities at 1.2 MHz are directly compared with arrays operating at 1.8 MHz in a flow phantom with attenuation comparable to the in vivo case. Contrast-enhanced imaging allowed visualization of arteries of the Circle of Willis in 5 of 5 subjects and 8 of 10 sides of the head despite probe placement outside of the acoustic window. Results suggest that this type of transducer may allow acquisition of useful images either in individuals with poor windows or outside of the temporal acoustic window in the field.
doi:10.1016/j.ultrasmedbio.2012.11.019
PMCID: PMC3764922  PMID: 23415287
Transcranial; Temporal acoustic window; Real-time 3-D ultrasound; Contrast-enhanced
2.  Pitch–Catch Phase Aberration Correction of Multiple Isoplanatic Patches for 3-D Transcranial Ultrasound Imaging 
Having previously presented the ultrasound brain helmet, a system for simultaneous 3-D ultrasound imaging via both temporal bone acoustic windows, the scanning geometry of this system is utilized to allow each matrix array to serve as a correction source for the opposing array. Aberration is estimated using cross-correlation of RF channel signals, followed by least mean squares solution of the resulting overdetermined system. Delay maps are updated and real-time 3-D scanning resumes. A first attempt is made at using multiple arrival time maps to correct multiple unique aberrators within a single transcranial imaging volume, i.e., several isoplanatic patches. This adaptive imaging technique, which uses steered unfocused waves transmitted by the opposing, or beacon, array, updates the transmit and receive delays of 5 isoplanatic patches within a 64° × 64° volume. In phantom experiments, color flow voxels above a common threshold have also increased by an average of 92%, whereas color flow variance decreased by an average of 10%. This approach has been applied to both temporal acoustic windows of two human subjects, yielding increases in echo brightness in 5 isoplanatic patches with a mean value of 24.3 ± 9.1%, suggesting that such a technique may be beneficial in the future for performing noninvasive 3-D color flow imaging of cerebrovascular disease, including stroke.
doi:10.1109/TUFFC.2013.2590
PMCID: PMC3843527  PMID: 23475914
3.  Ring Array Transducers for Real-Time 3D Imaging of an Atrial Septal Occluder 
Ultrasound in medicine & biology  2012;38(8):1483-1487.
We developed new miniature ring array transducers integrated into interventional device catheters such as used to deploy atrial septal occluders. Each ring array consisted of 55 elements operating near 5 MHz with interelement spacing of 0.20 mm. It was constructed on a flat piece of copper-clad polyimide and then wrapped around an 11 French O.D. catheter. We used a braided cabling technology from Tyco Electronics Corp to connect the elements to the Volumetrics Medical Imaging (VMI) real-time 3D ultrasound scanner. Transducer performance yielded a –6 dB fractional bandwidth of 20% centered at 4.7 MHz without a matching layer versus average bandwidth of 60% centered at 4.4 MHz with a matching layer. Real time 3D rendered images of an en face view of a Gore Helex septal occluder in a water tank showed a finer texture of the device surface from the ring array with the matching layer.
doi:10.1016/j.ultrasmedbio.2012.03.019
PMCID: PMC3434960  PMID: 22698504
2D array transducer; real-time 3D imaging; septal occluder
4.  3-D Ultrasound Guidance of Autonomous Robot for Location of Ferrous Shrapnel 
Vibrations can be induced in ferromagnetic shrapnel by a variable electromagnet. Real time 3-D color Doppler ultrasound located the induced motion in a needle fragment and determined its 3-D position in the scanner coordinates. This information was used to guide a robot which moved a probe to touch the shrapnel fragment.
doi:10.1109/TUFFC.2009.1185
PMCID: PMC2810201  PMID: 19574140
5.  Color Doppler Imaging of Cardiac Catheters Using Vibrating Motors 
Ultrasonic imaging  2008;30(4):247-250.
We attached a miniature motor rotating at 11,000 rpm onto the proximal end of cardiac electrophysiological (EP) catheters in order to produce vibrations at the tip which were then visualized by color Doppler on ultrasound scanners. We imaged the catheter tip within a vascular graft submerged in a water tank using the Volumetrics Medical Imaging 3D scanner, the Siemens Sonoline Antares 2D scanner, and the Philips ie33 3D ultrasound scanner with TEE probe. The vibrating catheter tip was visualized in each case though results varied with the color Doppler properties of the individual scanner.
PMCID: PMC2804844  PMID: 19514134
Color flow Doppler; device guidance; cardiac electrophysiology catheters
6.  Dual-mode IVUS Transducer for Image-Guided Brain Therapy: Preliminary Experiments 
Ultrasound in medicine & biology  2011;37(10):1667-1676.
In this study, we investigated the feasibility of using 3.5-Fr 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 to 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.
doi:10.1016/j.ultrasmedbio.2011.06.017
PMCID: PMC3177008  PMID: 21856073
dual-mode catheter transducer; ultrasound hyperthermia; intravascular ultrasound
7.  Progress in Ring Array Transducers for Real-Time 3D Ultrasound Guidance of Cardiac Interventional Devices 
Ultrasonic Imaging  2011;33(3):197-204.
As a treatment for aortic stenosis, several companies have recently introduced prosthetic heart valves designed to be deployed through a catheter using an intravenous or trans-apical approach. This procedure can either take the place of open heart surgery with some of the devices, or delay it with others. Real-time 3D ultrasound could enable continuous monitoring of these structures before, during and after deployment. We have developed a 2D ring array integrated with a 30 French catheter that is used for trans-apical prosthetic heart valve implantation. The transducer array was built using three 46 cm long flex circuits from MicroConnex (Snoqualmie, WA) which terminate in an interconnect that plugs directly into our system cable, thus no cable soldering is required. This transducer consists of 210 elements at .157 mm inter-element spacing and operates at 5 MHz. Average measured element bandwidth was 26% and average round-trip 50 Ohm insertion loss was -81.1 dB. The transducer were wrapped around the 1 cm diameter lumen of a heart valve deployment catheter. Prosthetic heart valve images were obtained in water tank studies.
PMCID: PMC3263761  PMID: 21842583
8.  New Fabrication Techniques for Ring-Array Transducers for Real-Time 3D Intravascular Ultrasound 
Ultrasonic imaging  2009;31(4):247-256.
We have previously described miniature 2D array transducers integrated into a Cook Medical, Inc. vena cava fi ter deployment device. While functional, the fabrication technique was very labor intensive and did not lend itself well to efficient fabrication of large numbers of devices. We developed two new fabrication methods that we believe can be used to efficiently manufacture these types of devices in greater than prototype numbers. One transducer consisted of 55 elements operating near 5 MHz. The interelement spacing is 0.20 mm. It was constructed on a flat piece of copper-clad polyimide and then wrapped around an 11 French catheter of a Cook Medical, Inc. inferior vena cava (IVC) filter deployment device. We used a braided wiring technology from Tyco Electronics Corp. to connect the elements to our real-time 3D ultrasound scanner. Typical measured transducer element band width was 20% centered at 4.7 MHz and the 50 Ω round trip insertion loss was -–82 dB. The mean of the nearest neighbor cross talk was –37.0 dB.
The second method consisted of a 46-cm long single layer flex circuit from MicroConnex that terminates in an interconnect that plugs directly into our system cable. This transducer had 70 elements at 0.157 mm interelement spacing operating at 4.8 MHz. Typical measured transducer element bandwidth was 29% and the 50 Ω round trip insertion loss was –83 dB. The mean of the nearest neighbor cross talk was –33.0 dB.
PMCID: PMC3057104  PMID: 20458877
2D array transducer; real-time 3D imaging; vena cava filter
9.  Simulation of Autonomous Robotic Multiple-Core Biopsy by 3D Ultrasound Guidance 
Ultrasonic imaging  2010;32(2):118-127.
An autonomous multiple-core biopsy system guided by real-time 3D ultrasound and operated by a robotic arm with 6+1 degrees of freedom has been developed. Using a specimen of turkey breast as a tissue phantom, our system was able to first autonomously locate the phantom in the image volume and then perform needle sticks in each of eight sectors in the phantom in a single session, with no human intervention required. Based on the fraction of eight sectors successfully sampled in an experiment of five trials, a success rate of 93% was recorded. This system could have relevance in clinical procedures that involve multiple needle-core sampling such as prostate or breast biopsy.
PMCID: PMC3018680  PMID: 20687279
3D ultrasound; computer-aided diagnosis; surgical robotics
10.  Dual-Mode IVUS Catheter for Intracranial Image-Guided Hyperthermia: Feasibility Study 
In this study, we investigated the feasibility of modifying 3-Fr IVUS catheters in several designs to potentially achieve minimally-invasive, endovascular access for image-guided ultrasound hyperthermia treatment of tumors in the brain. Using a plane wave approximation, target frequencies of 8.7 and 3.5 MHz were considered optimal for heating at depths (tumor sizes) of 1 and 2.5 cm, respectively. First, a 3.5-Fr IVUS catheter with a 0.7-mm diameter transducer (30 MHz nominal frequency) was driven at 8.6 MHz. Second, for a low-frequency design, a 220-μm-thick, 0.35 × 0.35-mm PZT-4 transducer—driven at width-mode resonance of 3.85 MHz—replaced a 40-MHz element in a 3.5-Fr coronary imaging catheter. Third, a 5 × 0.5-mm PZT-4 transducer was evaluated as the largest aperture geometry possible for a flexible 3-Fr IVUS catheter. Beam plots and on-axis heating profiles were simulated for each aperture, and test transducers were fabricated. The electrical impedance, impulse response, frequency response, maximum intensity, and mechanical index were measured to assess performance. For the 5 × 0.5-mm transducer, this testing also included mechanically scanning and reconstructing an image of a 2.5-cm-diameter cyst phantom as a preliminary measure of imaging potential.
doi:10.1109/TUFFC.2010.1723
PMCID: PMC3018697  PMID: 21041144
11.  3D Ultrasound Guidance of Autonomous Robotic Breast Biopsy: Feasibility Study 
Ultrasound in medicine & biology  2010;36(1):173-177.
Feasibility studies of autonomous robot biopsies in tissue have been conducted using real time 3D ultrasound combined with simple thresholding algorithms. The robot first autonomously processed 3D image volumes received from the ultrasound scanner to locate a metal rod target embedded in turkey breast tissue simulating a calcification, and in a separate experiment, the center of a water-filled void in the breast tissue simulating a cyst. In both experiments the robot then directed a needle to the desired target, with no user input required. Separate needle-touch experiments performed by the image-guided robot in a water tank yielded an rms error of 1.15 mm.
doi:10.1016/j.ultrasmedbio.2009.08.014
PMCID: PMC2800959  PMID: 19900753
3D ultrasound; surgical robotics; computer aided diagnosis
12.  Comparison of 3-D Multi-Lag Cross-Correlation and Speckle Brightness Aberration Correction Algorithms on Static and Moving Targets 
Phase correction has the potential to increase the image quality of 3-D ultrasound, especially transcranial ultrasound. We implemented and compared 2 algorithms for aberration correction, multi-lag cross-correlation and speckle brightness, using static and moving targets. We corrected three 75-ns rms electronic aberrators with full-width at half-maximum (FWHM) auto-correlation lengths of 1.35, 2.7, and 5.4 mm. Cross-correlation proved the better algorithm at 2.7 and 5.4 mm correlation lengths (P < 0.05). Static cross-correlation performed better than moving-target cross-correlation at the 2.7 mm correlation length (P < 0.05). Finally, we compared the static and moving-target cross-correlation on a flow phantom with a skull casting aberrator. Using signal from static targets, the correction resulted in an average contrast increase of 22.2%, compared with 13.2% using signal from moving targets. The contrast-to-noise ratio (CNR) increased by 20.5% and 12.8% using static and moving targets, respectively. Doppler signal strength increased by 5.6% and 4.9% for the static and moving-targets methods, respectively.
doi:10.1109/TUFFC.2009.1298
PMCID: PMC2814551  PMID: 19942503
13.  Dual-mode Intracranial Catheter Integrating 3D Ultrasound Imaging & Hyperthermia for Neuro-oncology: Feasibility Study 
Ultrasonic imaging  2009;31(2):81-100.
In this study, we investigated the feasibility of an intracranial catheter transducer with dual-mode capability of real-time 3D (RT3D) imaging and ultrasound hyperthermia, for application in the visualization and treatment of tumors in the brain. Feasibility is demonstrated in two ways: first by using a 50-element linear array transducer (17 mm × 3.1 mm aperture) operating at 4.4 MHz with our Volumetrics diagnostic scanner and custom electrical impedance matching circuits to achieve a temperature rise over 4°C in excised pork muscle, and second by designing and constructing a 12 Fr, integrated matrix and linear array catheter transducer prototype for combined RT3D imaging and heating capability. This dual-mode catheter incorporated 153 matrix array elements and 11 linear array elements diced on a 0.2 mm pitch, with a total aperture size of 8.4 mm × 2.3 mm. This array achieved a 3.5°C in vitro temperature rise at a 2 cm focal distance in tissue-mimicking material. The dual-mode catheter prototype was compared with a Siemens 10 Fr AcuNav™ catheter as a gold standard in experiments assessing image quality and therapeutic potential, and both probes were used in a canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating.
PMCID: PMC2810199  PMID: 19630251
catheter transducer; real-time 3D imaging; ultrasound hyperthermia; dual-mode array
14.  Real-Time 3D Intracranial Ultrasound with an Endoscopic Matrix Array Transducer 
Ultrasound in medicine & biology  2007;33(8):1277-1284.
A transducer originally designed for Transesophageal Echocardiography (TEE) was adapted for real-time volumetric endoscopic imaging of the brain. The transducer consists of a 36 × 36 array with an interelement spacing of 0.18 mm. There are 504 transmitting and 252 receive channels placed in a regular pattern in the array. The operating frequency is 4.5 MHz with a −6 dB bandwidth of 30%. The transducer is fabricated on a 10 layer flexible circuit from MicroConnex (Snoqualmie, WA). The purpose of this study is to evaluate the clinical feasibility of real-time 3D intracranial ultrasound with this device. The Volumetrics Medical Imaging (Durham, NC) 3D scanner was used to obtain images in a canine model. A transcalvarial acoustic window was created under general anesthesia in the animal laboratory by placing a 10 mm burr hole in the high parietal calvarium of a 50 kg canine subject. The burr-hole was placed in a left para-sagittal location to avoid the sagittal sinus, and the transducer was placed against the intact dura mater for ultrasound imaging. Images of the lateral ventricles were produced, including real-time 3D guidance of a needle puncture of one ventricle. In a second canine subject, contrast (Optison™, Amersham Health, Inc., Princeton, NJ) enhanced 3D Doppler color flow images were made of the cerebral vessels including the complete Circle of Willis. Clinical applications may include real-time 3D guidance of cerebral spinal fluid extraction from the lateral ventricles and bedside evaluation of critically ill patients where CT and MR imaging techniques are unavailable.
doi:10.1016/j.ultrasmedbio.2007.02.004
PMCID: PMC2755488  PMID: 17478032
Real-Time 3D Imaging; 2D Array Transducer; Intraoperative Guidance
15.  Real-Time 3D Contrast-Enhanced Transcranial Ultrasound and Aberration Correction 
Ultrasound in medicine & biology  2008;34(9):1387-1395.
Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3D transcranial ultrasound have shown advantages over traditional methods in a variety of cerebrovascular diseases. We present the results from a novel ultrasound technique, namely real-time 3D contrast-enhanced transcranial ultrasound. Using real-time 3D (RT3D) ultrasound and micro-bubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and 9 via the sub-occipital window and report our detection rates for the major cerebral vessels. In 71% of subjects, both of our observers identified the ipsilateral circle of Willis from the temporal window, and in 59% we imaged the entire circle of Willis. From the sub-occipital window, both observers detected the entire vertebrobasilar circulation in 22% of subjects, and in 44% the basilar artery. After performing phase aberration correction on one subject, we were able to increase the diagnostic value of the scan, detecting a vessel not present in the uncorrected scan. These preliminary results suggest that RT3D CE transcranial US and RT3D CE transcranial US with phase aberration correction have the potential to greatly impact the field of neurosonology.
doi:10.1016/j.ultrasmedbio.2008.01.015
PMCID: PMC2597560  PMID: 18395321
Transcranial; Ultrasound contrast; Intracranial Arteries; 3D Imaging; Phase Aberration
16.  Real-Time 3-D Ultrasound Guidance of Interventional Devices 
We have previously developed 2-D array transducers for many real-time volumetric imaging applications. These applications include transducers operating up to 7 MHz for transthoracic imaging, up to 15 MHz for intracardiac echocardiography (ICE), 5 MHz for transesophageal echocardiography (TEE) and intracranial imaging, and 7 MHz for laparoscopic ultrasound imaging (LUS). Now we have developed a new generation of miniature ring-array transducers integrated into the catheter deployment kits of interventional devices to enable real-time 3-D ultrasound scanning for improved guidance of minimally invasive procedures. We have constructed 3 new ring transducers. The first consists of 54 elements operating at 5 MHz. Typical measured transducer element bandwidth was 25%, and the 50 Ohm round trip insertion loss was −65 dB. Average nearest neighbor cross talk was −23.8 dB. The second is a prototype 108-element transducer operating at 5 MHz. The third is a prototype 108-element ring array with a transducer center frequency of 8.9 MHz and a −6 dB bandwidth of 25%. All transducers were integrated with an 8.5 French catheter sheath of a Cook Medical, Inc. vena cava filter deployment device.
doi:10.1109/TUFFC.898
PMCID: PMC2656286  PMID: 18986903
17.  Vibrating Interventional Device Detection Using Real-Time 3-D Color Doppler 
Ultrasound image guidance of interventional devices during minimally invasive surgery provides the clinician with improved soft tissue contrast while reducing ionizing radiation exposure. One problem with ultrasound image guidance is poor visualization of the device tip during the clinical procedure. We have described previously guidance of several interventional devices using a real-time 3-D (RT3-D) ultrasound system with 3-D color Doppler combined with the ColorMark technology. We then developed an analytical model for a vibrating needle to maximize the tip vibrations and improve the reliability and sensitivity of our technique. In this paper, we use the analytical model and improved radiofrequency (RF) and color Doppler filters to detect two different vibrating devices in water tank experiments as well as in an in vivo canine experiment. We performed water tank experiments with four different 3-D transducers: a 5 MHz transesophageal (TEE) probe, a 5 MHz transthoracic (TTE) probe, a 5 MHz intracardiac catheter (ICE) transducer, and a 2.5 MHz commercial TTE probe. Each transducer was used to scan an aortic graft suspended in the water tank. An atrial septal puncture needle and an endomyocardial biopsy forceps, each vibrating at 1.3 kHz, were inserted into the vascular graft and were tracked using 3-D color Doppler. Improved RF and wall filters increased the detected color Doppler sensitivity by 14 dB. In three simultaneous planes from the in vivo 3-D scan, we identified both the septal puncture needle and the biopsy forceps within the right atrium using the 2.5 MHz probe. A new display filter was used to suppress the unwanted flash artifact associated with physiological motion.
doi:10.1109/TUFFC.2008.798
PMCID: PMC2639786  PMID: 18599423
18.  The Ultrasound Brain Helmet: New Transducers and Volume Registration for In Vivo Simultaneous Multi-Transducer 3-D Transcranial Imaging 
Because stroke remains an important and time-sensitive health concern in developed nations, we present a system capable of fusing 3-D transcranial ultrasound volumes acquired from two sides of the head. This system uses custom sparse array transducers built on flexible multilayer circuits that can be positioned for simultaneous imaging through both temporal acoustic windows, allowing for potential registration of multiple real-time 3-D scans of cerebral vasculature. We examine hardware considerations for new matrix arrays—transducer design and interconnects—in this application. Specifically, it is proposed that SNR may be increased by reducing the length of probe cables. This claim is evaluated as part of the presented system through simulation, experimental data, and in vivo imaging. Ultimately, gains in SNR of 7 dB are realized by replacing a standard probe cable with a much shorter flex interconnect; higher gains may be possible using ribbon-based probe cables. In vivo images are presented, showing cerebral arteries with and without the use of microbubble contrast agent; they have been registered and fused using a simple algorithm which maximizes normalized cross-correlation.
doi:10.1109/TUFFC.2011.1929
PMCID: PMC3271736  PMID: 21693401

Results 1-18 (18)