Interview by JOHN BROSKY,

Changing the paradigm in ultrasound, imaging

Dr. Jacques Souquet received a golden handshake, as they say in France, from Royal Philips Electronics 10 years ago when the Dutch giant acquired ATL Ultrasound. After paying out his interest in ATL, Philips brought Souquet on board in 2000 as chief scientific and technology officer and senior vice president of Philips Medical Systems, a position he held for the next five years.

In 2005 he left Philips to start SuperSonic Imagine (Aix-en-Provence, France), raising €10 million ($12 million in 2006) in a Series A financing round to develop "revolutionary medical ultrasound technology." This revolution, called Aixplorer, was unveiled in 2008 in Chicago at the Radiological Society of North America annual exposition and enabled SuperSonic to raise another €20 million ($28 million in 2008) in a second financing round in the middle of the financial market collapse from the likes of Edmond de Rothschild Investment Partners and Wellington Partners Venture Capital.

Souquet is member of the board of directors of SonoSite, the creator of the portable ultrasound category and one of the leading players in that segment. He is also on the board of Median Technologies, a French company developing computer-assisted diagnostic systems. He is the inventor of the multiplane transesophageal echo probe, used currently in 30% of all ultrasound echocardiography examinations.

The recipient of 10 patents in the field of ultrasound imaging, Souquet is the author of more than 50 technical papers. A graduate of the Ecole Supérieure d'Electricité in Paris, he earned his first PhD from Orsay University of France in the field of optical memory, and then a second PhD from Stanford University in the field of new acoustic imaging techniques for medical ultrasound applications and nondestructive testing.

BB&T interviewed Souquet during the European Congress of Radiology in Vienna, where he was presenting the Aixplorer.

BB&T: What is Aixplorer bringing to ultrasound that makes it 'revolutionary?'

Souquet: First off, Aixplorer streamlines ultrasound technology with simple hardware, and then greatly enhances it with advanced software. With conventional ultrasound there are anywhere from five to 10 computer boards built into the unit. We do not have that. Instead we have a single board for acquisition, that I would call a 'dumb' board, though I should probably not say that. The data is transferred over a BUS to an off-the-shelf video gaming board. This configuration is faster, more flexible and can be programmed with new modes for very, very fast imaging. Aixplorer streamlines ultrasound technology even further by requiring no hardware for beam formation. As for transducer, it is made of a composite material by a French company called Vermon that is every bit as good as a single crystal transducer.

BB&T: According to your competitors here at ECR, elastography is the must-have feature for ultrasound as it creates a new capability for characterizing tumors. And they say Aixplorer takes elastography to a new level. Can you explain?

Souquet: Elasticity changes the paradigm in ultrasound, yes, and it does so without hardware. Clearly we believe elastography is the must-have feature for ultrasound moving forward. Every ultrasound will have to support this feature. GE Healthcare and Philips do not have this capability right now and I know that they are suffering because of it. In Europe elastography is starting to take sales away from companies without elastography. We won two contracts in France beating out Siemens because of elastography. It is true we have a home court advantage there. But we have also won in Germany against Siemens.

Elastography, introduced by Hitachi in 2004, and imitated by other since, is based on the compression model and is heavily dependent on the skill and experience of the radiologist using the transducer. The Aixplorer uses a shear wave pulse that you can think of as ripples in a pond. The shear wave is sent at super sonic speeds into different depths of tissue creating a Mach cone and the ripples it sets off have a velocity that is between five and seven meters per second. We then use a standard ultrasound B-mode wave that moves at 1,500 meters per second to read the slower shear wave. This provides quantitative results that are not subjective and are reproducible, as opposed to the compression method that is not quantifiable, not reproducible and creates a lot of artifacts in the images.

The second difference that distinguishes our shear wave platform is that where conventional ultrasound is typically reading 128 lines at 200 to 500 frames per second, Aixplorer is acquiring 10,000 frames per second making it 20 times faster. In addition, we are receiving the data in kilopascal, which is a measure of pressure. So the difference is that the physical force compression method provides a global assessment of tissue deformation where shear wave pulse provides a local assessment of lesion stiffness. And when I say local, I mean that every micro point in our image returns a number, which is what is meant when we say we produce a quantifiable measure.

BB&T: The only other manufacturer featuring an ultrasound shear wave, rather than relying on the compression method, is Siemens with ARFI (Acoustical Radiation Force Impulse) that is currently being reviewed by the Food & Drug Administration.

Souquet: ARFI was actually developed at Duke University and it is not exactly the same technology as Aixplorer, though they do use a shear wave. Siemens shoots and measures on the same line where the Aixplorer shear wave is launched into tissue based on a unique patent using a long pulse similar to a Doppler and builds a 2-D shear wave image by measuring the waves moving perpendicular to the pulse wave that sets off the rippling effect. All of which means Aixplorer returns a superior image. Siemens is also having a problem with the increasing temperature of their probe during an examination and this means that a cool-down period is required during the exam.

Finally, anyone who is going to generate a true ultrasound shear wave, as opposed to the compression method that measures elasticity using the physical force of pressing down on an organ, will have to talk sooner or later with Armen Sarvazyan, who holds the key patent and is a founder of SuperSonic Imagine. This is why Siemens, even with an FDA approval for its ARFI system, can not put the units on the market, because they do not yet have an agreement with Armen.

BB&T: Elastography seems to be taking ultrasound in new, and unexpected directions. At ECR 200,9 TomTec and Bracco are demonstrating a new technique for characterizing liver tumors using a contrast agent. And recently Theraclion announced a partnership with your company to integrate elastography with high frequency ultrasound (HIFU) therapy.

Souquet: If there is a place measuring elasticity can play an important role in medicine it is with therapeutic devices. HIFU treatment of tumors or other tissue is a lot like using a microwave oven where something is soft when it is first heated but then becomes hard afterwards. Elastography can determine this stiffness and show the radiologist or HIFU therapist the effect of the therapy. The project with Theraclion combines stereotactic targeting for HIFU with Aixplorer and will provide immediate feedback for hyperparathyroidism treatment rather than waiting weeks for lab reports on blood tests. We are currently developing HIFU for the brain.

Using elastography as a tool with contrast enhanced ultrasound (CEUS) is a brand new area for theranostics [measuring the efficacy of therapeutics using therapeutic-specific diagnostic tools]. We have a relationship with TomTec and as part of our collaboration we are also talking with Bracco, so you can expect to being hearing more about developments in this area. We also have a relationship established with bioMérieux, which is very active in theranostics. And we also brought on staff the CEUS guru from Philips who just moved his family to the south of France to join us.

Developing our elastography platform we have a deep relationship with the École Supérieure de Physique et de Chimie Industrielles (ESPCI), which is located in the Nobel Prize Corner of Paris where Marie Curie did her work, and many others. Working with this lab we have developed unique patents on shear wave, 11 of which are our own and 10 that we purchased from the Centre National de Recherche Scientifique.

BB&T: The near-term focus for Aixplorer is competing in the mammography space. You are leading a presentation here at ECR 2009 called "On the Move – Where will SuperSonic Imagine take Breast Ultrasound." What is the potential you see here?

Souquet: The gold standard for mammography remains X-ray examination. And today when a tumor is suspected, the patient is sent to a diagnostic center for an ultrasound exam to characterizes the tumor. If a tumor is detected, the patient then needs a biopsy. In the United States, there are 2 million breast biopsies performed each year, yet 80% of these biopsies return negative results. That is a heavy cost to the healthcare system. If we are able to clinically demonstrate that we can reduce the number of biopsies required, that could represent significant savings for healthcare systems not only in the U.S. but around the world.

We are currently conducting a multicenter study of the breast using shear wave from the Aixplorer. Seventeen leading research and reference hospitals are participating with seven in the United States and 10 in Europe, primarily in France, Germany, Italy and the UK. The endpoint is to demonstrate the specificity of the shear wave exam in detecting tumors in the breast. We have already reviewed exams from 1,000 patients in this study and the study design is for 2,300 patients, which we expect to complete by July.

The group participating in our study at Hammersmith-Charring Cross Hospital (London) estimates the reduction in biopsies could be as high as 50%. Our partner hospitals in the United States are more conservative, saying it could be between 30%and 40%. After, and if, we demonstrate the effectiveness for breast examinations, we plan to move on to the prostate and the liver.

BB&T: You said earlier you have scored some sales successes and will soon begin shipments of Aixplorer. Are you hitting the sales targets your investors are hoping to see?

Souquet: Our sales funnel has exceeded our expectations for the first three months of this year and we are now building up the capacity to meet this kind of demand. The first Aixplorer will ship this month (March 2009). We have the CE mark and are negotiating a 510(k) with the FDA using the approval. Siemens received approval 18 months ago for their compression method of the S2000 so that is our predicate device. Our filing is for the same intended use, just with a different approach.

Elastography is not going to suddenly push ultrasound to 10-times growth, but it will strongly contribute to double-digit growth in sales. I am sure about that.