Intracranial dual-mode IVUS and hyperthermia using circular arrays: preliminary experiments.

In this study, we investigated the feasibility of using 3.5-Fr (3 Fr = 1 mm) circular phased-array intravascular ultrasound (IVUS) catheters for minimally invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated in two ways: (1) by inserting a 3.5-Fr IVUS catheter through skull burr holes, for 20 MHz brain imaging in the pig model, and (2) by testing a modified circular array for therapy potential with 18.5-MHz and 9-MHz continuous wave (CW) excitation. The imaging transducer's performance was superior to our previous 9-MHz mechanical IVUS prototype. The therapy catheter transducer was driven by CW electrical power at 18.5 MHz, achieving temperature changes reaching +8°C at a depth of 2 mm in a human glioblastoma grown on the flank of a mouse with minimal transducer resistive heating of +2°C. Further hyperthermia trials showed that 9-MHz CW excitation produced temperature changes of +4.5°C at a depth of 12 mm-a sufficient temperature rise for our long-term goal of targeted, controlled drug release via thermosensitive liposomes for therapeutic treatment of 1-cm-diameter glioblastomas.

Ring array transducers for real-time 3-D imaging of an atrial septal occluder.

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 Corporation to connect the elements to the Volumetric Medical Imaging (VMI) real-time 3-D ultrasound scanner. Transducer performance yielded a -6 dB fractional bandwidth of 20% centered at 4.7 MHz without a matching layer vs. average bandwidth of 60% centered at 4.4 MHz with a matching layer. Real-time 3-D 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.

Progress in ring array transducers for real-time 3D ultrasound guidance of cardiac interventional devices.

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 transapical approach. This procedure can either take the place of open heart surgery with some ofthe 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 transapical 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 0.157 mm interelement spacing and operates at 5 MHz. Average measured element bandwidth was 26% and average round-trip 50 ohm insertion loss was -58.1 dB after correcting for diffractive losses. The transducer was wrapped around the 1 cm diameter lumen of a heart-valve deployment catheter. Prosthetic heart valve images were obtained in water-tank studies.

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.

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.

Simulation of autonomous robotic multiple-core biopsy by 3D ultrasound guidance.

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.

Three-dimensional ultrasound guidance of autonomous robotic breast biopsy: feasibility study.

Feasibility studies of autonomous robot biopsies in tissue have been conducted using real-time three-dimensional (3-D) ultrasound combined with simple thresholding algorithms. The robot first autonomously processed 3-D 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. (E-mail: kaicheng.liang@duke.edu).

Dual-mode intracranial catheter integrating 3D ultrasound imaging and hyperthermia for neuro-oncology: feasibility study.

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 x 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 degrees 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 x 2.3 mm. This 3.64 MHz array achieved a 3.5 degrees 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 an in vivo canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating.

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.

The ultrasound brain helmet: feasibility study of multiple simultaneous 3D scans of cerebral vasculature.

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time three-dimensional (3D) scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging (Durham, NC, USA) real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64 degrees pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128 degrees sector, two simultaneous parasagittal images merged into a 128 degrees x 64 degrees C-mode plane and a simultaneous 64 degrees axial image. Real-time 3D color Doppler scans from a skull phantom with latex blood vessel were obtained after contrast agent injection as a proof of concept. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

New fabrication techniques for ring-array transducers for real-time 3D intravascular ultrasound.

We have previously described miniature 2D array transducers integrated into a Cook Medical, Inc. vena cava filter 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 bandwidth was 20% centered at 4.7 MHz and the 50 Omega 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 Omega round trip insertion loss was -83 dB. The mean of the nearest neighbor cross talk was -33.0 dB.

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.

Color Doppler imaging of cardiac catheters using vibrating motors.

A miniature motor rotating at 11,000 rpm was attached onto the proximal end of cardiac electrophysiological (EP) catheters in order to produce vibrations at the tip that were then visualized by color Doppler on ultrasound scanners. The catheter tip was imaged 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, although results varied with the color Doppler properties of the individual scanner.

Ultrasound probe with integrated ECG lead: feasibility study.

We integrated electrocardiogram (ECG) leads onto the face of a cardiac ultrasound transducer and the exterior chassis of a simulated small, portable scanner to minimize the number of devices needed to collect cardiac information. Since the ECG leads were not placed on their standard locations, a precordial ECG was recorded.

Real-time 3-d intracranial ultrasound with an endoscopic matrix array transducer.

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 x 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, USA). The purpose of this study is to evaluate the clinical feasibility of real-time 3-D intracranial ultrasound with this device. The Volumetrics Medical Imaging (Durham, NC, USA) 3-D 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 parasagittal 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 3-D guidance of a needle puncture of one ventricle. In a second canine subject, contrast-enhanced 3-D Doppler color flow images were made of the cerebral vessels including the complete Circle of Willis. Clinical applications may include real-time 3-D guidance of cerebrospinal fluid extraction from the lateral ventricles and bedside evaluation of critically ill patients where computed tomography and magnetic resonance imaging techniques are unavailable.

3-D ultrasound guidance of surgical robotics: a feasibility study.

Laparoscopic ultrasound has seen increased use as a surgical aide in general, gynecological, and urological procedures. The application of real-time, three-dimensional (RT3D) ultrasound to these laparoscopic procedures may increase information available to the surgeon and serve as an additional intraoperative guidance tool. The integration of RT3D with recent advances in robotic surgery also can increase automation and ease of use. In this study, a 1-cm diameter probe for RT3D has been used laparoscopically for in vivo imaging of a canine. The probe, which operates at 5 MHz, was used to image the spleen, liver, and gall bladder as well as to guide surgical instruments. Furthermore, the three-dimensional (3-D) measurement system of the volumetric scanner used with this probe was tested as a guidance mechanism for a robotic linear motion system in order to simulate the feasibility of RT3D/robotic surgery integration. Using images acquired with the 3-D laparoscopic ultrasound device, coordinates were acquired by the scanner and used to direct a robotically controlled needle toward desired in vitro targets as well as targets in a post-mortem canine. The rms error for these measurements was 1.34 mm using optical alignment and 0.76 mm using ultrasound alignment.

Real-time, 3-D ultrasound with multiple transducer arrays.

Modifications were made to a commercial real-time, three-dimensional (3-D) ultrasound system for near simultaneous 3-D scanning with two matrix array transducers. As a first illustration, a transducer cable assembly was modified to incorporate two independent, 3-D intra-cardiac echo catheters, a 7 Fr (2.3 mm O.D.) side scanning catheter and a 14 Fr (4.7 mm O.D) forward viewing catheter with accessory port, each catheter using 85 channels operating at 5 MHz. For applications in treatment of atrial fibrillation, the goal is to place the sideviewing catheter within the coronary sinus to view the whole left atrium, including a pulmonary vein. Meanwhile, the forward-viewing catheter inserted within the left atrium is directed toward the ostium of a pulmonary vein for therapy using the integrated accessory port. Using preloaded, phasing data, the scanner switches between catheters automatically, at the push of a button, with a delay of about 1 second, so that the clinician can view the therapy catheter with the coronary sinus catheter and vice versa. Preliminary imaging studies in a tissue phantom and in vivo show that our system successfully guided the forward-viewing catheter toward a target while being imaged with the sideviewing catheter. The forward-viewing catheter then was activated to monitor the target while we mimicked therapy delivery. In the future, the system will switch between 3-D probes on a line-by-line basis and display both volumes simultaneously.

Real-time 3D laparoscopic ultrasonography.

We have previously described 2D array ultrasound transducers operating up to 10 MHz for applications including real time 3D transthoracic imaging, real time volumetric intracardiac echocardiography (ICE), real time 3D intravascular ultrasound (IVUS) imaging, and real time 3D transesophageal echocardiography (TEE). We have recently built a pair of 2D array transducers for real time 3D laparoscopic ultrasonography (3D LUS). These transducers are intended to be placed down a trocar during minimally invasive surgery. The first is a forward viewing 5 MHz, 11 x 19 array with 198 operating elements. It was built on an 8 layer multilayer flex circuit. The interelement spacing is 0.20 mm yielding an aperture that is 2.2 mm x 3.8 mm. The O.D. of the completed transducer is 10.2 mm and includes a 2 mm tool port. The average measured center frequency is 4.5 MHz, and the -6 dB bandwidth ranges from 15% to 30%. The 50 omega insertion loss, including Gore MicroFlat cabling, is -81.2 dB. The second transducer is a 7 MHz, 36 x 36 array with 504 operating elements. It was built upon a 10 layer multilayer flex circuit. This transducer is in the forward viewing configuration and the interelement spacing is 0.18 mm. The total aperture size is 6.48 mm x 6.48 mm. The O.D. of the completed transducer is 11.4 mm. The average measured center frequency is 7.2 MHz, and the -6 dB bandwidth ranges from 18% to 33%. The 50 omega insertion loss is -79.5 dB, including Gore MicroFlat cable. Real-time in vivo 3D images of canine hearts have been made including an apical 4-chamber view from a substernal access with the first transducer to monitor cardiac function. In addition, we produced real time 3D rendered images of the right pulmonary veins from a right parastemal access with the second transducer, which would be valuable in the guidance of cardiac ablation catheters for treatment of atrial fibrillation.

Feasibility study: real-time 3-D ultrasound imaging of the brain.

We tested the feasibility of real-time, 3-D ultrasound (US) imaging in the brain. The 3-D scanner uses a matrix phased-array transducer of 512 transmit channels and 256 receive channels operating at 2.5 MHz with a 15-mm diameter footprint. The real-time system scans a 65 degrees pyramid, producing up to 30 volumetric scans per second, and features up to five image planes as well as 3-D rendering, 3-D pulsed-wave and color Doppler. In a human subject, the real-time 3-D scans produced simultaneous transcranial horizontal (axial), coronal and sagittal image planes and real-time volume-rendered images of the gross anatomy of the brain. In a transcranial sheep model, we obtained real-time 3-D color flow Doppler scans and perfusion images using bolus injection of contrast agents into the internal carotid artery.

Two dimensional arrays for real time 3D intravascular ultrasound.

We have previously described 2D arrays operating at up to 10.0 MHz consisting of several thousand elements for transthoracic cardiac imaging and over a hundred elements for intracardiac imaging using 7 Fr to 12 Fr catheters. We have begun to explore forward viewing real time 3D phased array intravascular ultrasound, which may require imaging depths of a few centimeters to look down the axis of a vessel to view vulnerable atherosclerotic plaque. We used a noncoaxial based cable technology that allowed 100 signal wires to be placed inside a4.8 French IVUS lumen with an inner diameter of 1.3 mm. We pursued two different fabrication technologies for the building of the transducers. Each transducer was constructed in the forward viewing configuration to allow simultaneous real time B-scans, C-scans and volumetric rendering of vessels and vascular stents distal to the catheter tip. In order to obtain the desired penetration depth, each transducer was constructed to operate at 10.0 MHz. The first method included an ordered array of 11 x 11 = 121 elements. In order to conform to the round aperture of the IVUS lumen, the comers were cut off, resulting in a total of 97 signal channels. Real time images include a 4 mm diameter vessel in a tissue mimicking phantom, an expanded stent and a stent in an excised sheep aorta. The second method is based upon a laser dicing technique that cuts the individual elements in a random pattern. This resulted in 61 signal channels. Real time 3D images of the AIUM test object were made with this transducer.