James B. Seward, M.D., holds
Acuson’s AcuNav digital ultrasound catheter.
The role of ultrasound in cardiac and intravascular imaging is getting smaller, not from a market or clinical standpoint, but certainly from a technological perspective.
Helping to prove that smaller is better, James B. Seward, M.D., director of the Echocardiography Laboratory at Mayo Clinic (Rochester, Minn.) and professor of medicine and pediatrics, and Douglas L. Packer, M.D., co-director of cardiac electrophysiology (EP) and director of EP research at Mayo Clinic and professor of medicine, have worked during the last eight years to develop a diagnostic ultrasound catheter.
In December, the FDA awarded Acuson Corp. (Mountain View, Calif.) (with whom Mayo has a technology licensing contract) 510(k) marketing clearance for the device named AcuNav.
From a business perspective, this device provides Acuson its first entry into the disposable device market.
Clinically, AcuNav miniaturizes phased-array technology in an ultrasound transducer and puts it into a catheter for imaging the interior of the heart. The catheter is inserted in the femoral artery or the jugular vein and threaded into the right atrium or right ventricle of the heart. By recording Doppler signals, the device obtains information about blood flow and provides images of the interior of the heart.
With up to 15 cm of penetration, AcuNav can image the entire heart from the right side, thus providing physicians with a complete view of the structure of the heart.
The device also can image objects in the heart, such as catheters, valves and angioplasty devices – in the heart. In clinical trials, AcuNav successfully imaged 88 of these devices. The studies obtained more than 1,400 images.? Imaging within the heart may be just the beginning of the potential applications of AcuNav.
Medical Imaging spoke with Drs. Seward and Packer about their vision for intravascular ultrasound.
How did the concept for the AcuNav digital ultrasound catheter begin?
Seward: Echocardiography is usually performed on the surface of the chest. Years ago, it was realized that the transducer could be miniaturized. Attempts to do this began in 1970 and resulted in transesophageal echocardiography, which, by 1989, was introduced as a clinical procedure. With this procedure, a small transducer is put on a gastroenterologist’s tube and put down the esophagus (the patient has to swallow the tube) to take pictures of the heart.
The idea was to develop even smaller tubes, ones small enough that they could be placed inside blood vessels and the heart, even in the coronary arteries.
The miniaturized transducer consists of a single crystal, 1 or 2 millimeters in diameter that rotates like a propeller, examining around a shaft and creates an image that resembles a coin. It is ideal for examining the interior of blood vessels.
This technology is comparable to transesophageal echo, which utilized more sophisticated transducer technology.
Douglas L. Packer, M.D.
Packer: In 1991, we started performing accessory pathway ablations. We had done this kind of procedure surgically and were enthusiastic about moving forward with a catheter-based approach. In some of the early patients, we used transesophageal echocardiography to follow the procedure.
One obvious finding was that we could see the catheter tip during the interaction with the tip and the tissue to be ablated. Most spectacular was the finding that we also could see the lesion produced by radiofrequency energy evolve. Also, we could see the consequence of generating too much heat.
We thought that if we could put this technology on a catheter, it would be easier and more comfortable for the patient. This was consistent with what Dr. Seward had been thinking for about a year or two about trying to get this [device] inside a blood vessel.
We began to work with Acuson and its chief engineer, Michael Curley, (Acuson’s program director for the interventional devices business). He came up with the initial prototype – a rigid stainless steel, 24 French tube. We started testing this device toward the end of 1993 and obtained spectacular images.
We used the device in a variety of studies in animals to give us a relatively noninvasive way to look at the hearts in general and in particular, the functions and the electrophysiologic changes with the ablations we were performing.
Seward: Think of blood vessels as conduits that allow you to travel throughout the body, looking inside blood vessels and through blood vessels into the surrounding tissue. The unique feature of the catheter is that it has deep penetration, up to 15 cm or so.
For example, if the device is in the abdominal aorta, you can see well into the tissues around the aorta. If the device is in one heart chamber, you can see from that chamber into another. The device also has color flow Doppler, so you can see the movement of blood. It is a full complement ultrasound transducer attached to a catheter.
Packer: Through the interaction between Mayo and Acuson, a catheter – complete with handle, mechanisms and knobs – was designed. We started our human clinical trial about a year ago.
Have there been any unexpected benefits and surprises?
Seward: A common procedure for treating arrhythmias of the heart is ablation; that is, destroying some tissue to prevent the arrhythmia.
When the inside is heated, bubbles are produced. This fascinated us from the outset. We initially described it as “boiling blood.” In fact, it is nitrogen coming out of solution.
If the catheter is placed in the heart muscle, the gas that is generated creates a small explosion. The risks of ablation include injury and thrombus formation. You can see this happening, and this has led us to change the approach of certain procedures.
The new catheter provides very precise localization and you can see the phenomenon that occurs in conjunction with a procedure. This technology is like having eyes. Until now, we were confined to projection imagery, such as fluoroscopy. You knew where you were, but you could not – in any precise way – see what you were doing. It was like having a map, but not being able to look out the car window.
Packer: As time went on, it became more and more clear that we were designing this device for intervention. With the work we have done, the images have been fairly spectacular. The device shows the physiology of ablation and enables us to position catheters in the heart and to locate them next to specific anatomical targets. It also enables us to see the endocardial surface very well and to position the catheter tip with specific orientation on the endocardial surface. The device allows us to look at the effect of energy delivery at that site.
A big surprise was how well the device showed events we did not know existed. We knew that blood probably boiled at the interface between the tissue and the catheter tip, but had no idea what the consequence of that event would be for the tissue.
A straightforward outcome has been that we can see what the consequence is. Thus, we could understand it and view the evolution of the problem and begin to take preventive measures.
Also, the device allows us to see the lesion and makes the correlation between what we see on echocardiography and on pathologic examination of the tissue. Thus, we have immediate feedback about the adequacy of the lesion.
We also have found the device quite useful in animal models to help us position more complicated interventional catheters and devices and to identify predictors that what we had done would be effective or not effective.
So, we have conducted a series of studies and have found that one can act on the physiology observed and act on it to improve the outcome of the ablation. Obviously, additional studies will be required to demonstrate the safety and efficacy of guiding ablation procedures in patients with arrhythmias.
How extensively was AcuNav used in the animal and human trials?
Seward: Ninety-eight percent of the procedures have been performed in animals. There have been only a few human procedures, but what occurs in animals also occurs in humans. This device creates a visual experience. If you see a bump, you can navigate precisely to it, do something, and see what changes occur at that bump.
Packer: The clinical trial was an effectiveness and safety study of the imaging of cardiac structures and other medical devices. One of the strengths of the system is that all the images were obtained from the right side of the heart. We did not enter any artery, mainly because we did not need to. We could view the arterial system, as well as the left ventricle, from the right atrial imaging venue.
One of the advantages of phased-array echocardiography is that the penetration is substantially better than it is with the mechanically driven, single piece of electric crystal rotational system. So, instead of getting 2 cm or 3 cm – maybe 4 cm – of penetration, the phased array provides up to 14 cm or 15 cm of penetration.
The phased-array approach also helped us look at physiology through color flow, pulsed wave Doppler and Doppler tissue velocity and acceleration, all in cooperation with simultaneous imaging.
To what extent has AcuNav been used on human patients?
Seward: That information is controlled by the FDA, but I can tell you it is fewer than 50 patients. The FDA determines the number of cases. That number will not be released until we get to a clinical setting.
How difficult is this device to use? What kind of training is involved?
Packer: It would depend on one’s level of prior experience. Some gifted interventionalists can place a catheter virtually anywhere. They will have relatively little difficulty with manipulating the ultrasound catheter. Even the novice will not have trouble manipulating the catheter, because the tip of the catheter can be deflected in four directions.
It is essentially the same as using any other catheter?
Packer: The issue is obtaining the image views. For example, if one wanted to look at the left superior pulmonary vein, the imager would need to know how to obtain those images. If someone is an experienced echocardiographer, that process will be straightforward.
If the new user is an interventionalist with little echocardiography experience, he or she will need to undertake studies with the help of echocardiography colleagues. There clearly will be a learning phase.
How did your interest come about in this area?
Seward: The development of this device was the evolution of the technology of miniaturization. Any time an operation is performed on the heart, the heart has to be opened and all the blood has to be washed out, because the surgeon cannot see through the blood. With this device, ultrasound can “see” through blood; thus, you can navigate inside the heart and perform procedures through the black space of blood without removing blood from the heart. No other technology I am aware of can do this in this small configuration. MRI and CT, for example, cannot be miniaturized and put on a catheter, as this device is.
What do you foresee as the next logical step for intravascular ultrasound?
Seward: If you have a means of seeing, you can imagine that you probably will want to see better, to navigate to specific places and to control the intervention. Right now, you can see but the seeing does not control the device.
Today, ultrasound is essentially 2D; it is tomographic. You would want it to be 3D or to have wider field-of-view or binocular vision. That technology will come along, but it will be a while.
Packer: We have initiated a series of studies in which we have looked at using this kind of technology to guide transvascular myocardial revascularization procedures that are performed in cardiac catheterization labs. The idea is that if we can go in and create extra channels into the tissue, it will be a way to revascularize above and beyond what can be done with bypass grafting or angioplasty. I anticipate that this device will be used extensively in guiding such a therapeutic procedure.
Currently, we are looking at using the device for 4D and 5D virtual reality imaging, so we can gather information on the structure of the heart, reconfigure it into a 3D image and then get inside the heart through virtual reality techniques.
I think the system also will be used in the course of interventional procedures to correct heart valve problems. Also, there are myriad applications for use in the liver, bladder, esophagus or other organ systems.
What other projects are you involved with regarding imaging the heart?
Packer: We are continuing to study intracardiac ultrasound for guiding ablation. One of the most promising things we are doing is the 3D virtual reality project I mentioned. We are doing that with electron-beam CT, ultrasound and MRI to obtain the anatomical images. We are creating a 3D image of the heart and then creating fourth, fifth and sixth dimensions by acquiring physiological information from other mechanisms.
Over the next four or five years, you will be able to go into a catheterization lab and put on virtual reality goggles. It will be very much like walking into the heart and navigating around within it, much the same way you would walk in a room.
How soon do you see the 4D, 5D or 6D technologies coming to fruition?
Packer: I think we’ll have prototypes developed within a couple of years. They will be crude, as you would expect, but we are making progress.
