Ultrasound tags breast tumors

About 46,000 women and 300 men die of breast cancer annually. It's the most common form of cancer among American women--indeed, the most common in women worldwide. Each year, physicians diagnose approximately 180,000 new cases of breast cancer in women and some 1,000 among men.

A new approach to ultrasound imaging will give physicians another weapon in their battle against breast cancer. Developed by Advanced Technology Laboratories, Bothell, WA, high definition ultrasound imaging can help doctors differentiate between malignant breast lesions and benign masses. This all-digital imaging technology enhances image definition by capturing much more of the information returning to the system's scanhead than a conventional ultrasound system. It will change the way doctors evaluate a possible breast tumor.

Typically, doctors employ screening mammograms (x-ray examinations of the breasts) to detect breast lesions, and then employ diagnostic mammograms to investigate abnormal masses detected by the screening mammograms. When the physician who reads a mammogram suspects cancer, the next step is a biopsy. Biopsy involves either doing surgery on the patient's breast and removing tissue for study, or pushing a needle into the possible cancer and retrieving a sample.

Surgical biopsies cost $2,500 to $5,000 and needle biopsies from $750 to $1,000. Both procedures involve pain, possible breast deformation, and scarring. Should the biopsy prove negative, internal scars can make future mammograms harder to read. Also, on average, some 80% of tumors biopsied prove benign, and 20% malignant. In the United States, biopsies cost more than $1 billion annually.

Clearly, doctors need a technique that will enable them to avoid doing biopsies on benign tumors, but that will help them recognize malignancies.

Diagnosing with ultrasound. Conventional ultrasonic studies have been used to evaluate breast disease for many years. Ultrasound has advantages: An examination costs $75 to $300, and it's painless. Unfortunately, a conventional system's limited image detail restricts it to use as a guide during needle-biopsy procedures, and to differentiating between fluid-filled cysts and solid masses.

All ultrasound systems use beamformers and scanheads to direct ultrasonic energy into a patient's body, and then receive the returning echo. A beamformer functions as the acoustic lens of the ultrasound system. It transmits and receives a spectrum of ultrasonic frequencies via a scanhead.

To obtain an image of a specific part of a patient's body, a doctor places the ultrasound system's scanhead against the patient's skin. The beamformer steers and focuses the ultrasonic beam. Echoes from the patient's tissues, organs, and blood flow return to the scanhead, and the beamformer's receiving channels combine echo information from scanhead elements to form an ultrasound image.

Blurry vision. Beamformers pulse transducer elements in the ultrasonic scanhead to produce ultrasound. Echoes return to the scanhead separated in time. The beamformer delays these echoes, so that after summing all channels, the system compensates for the time variations in the signals, and doctors get a clear image. But the beamformer must preserve as much of the returning signal's bandwidth as possible, and prevent distortion of echoes during delay.

Analog time delay lines consist of copper wire (about 50 inches long) coiled around a ferrite core. The system includes a contact soldered to the wire for each time delay required by every element of every scanhead used. An analog beamformer's accuracy degrades as delay time increases, limiting the bandwidth that can be processed.

At low frequencies, the backscatter properties of breast tumor tissue almost match those of breast fat. But the frequency dependence of backscatter from an infiltrating breast cancer is half that of fat, so ultrasound can differentiate between the two types of tissue at higher frequencies. Thus it's very important to preserve the broadest possible range of frequencies returned to the system, if you wish to see small differences in tissue composition.

Advanced Technology Laboratories' digital ultrasonic system is free from the bandwidth limitations inherent to analog ultrasound systems. It performs an A/D conversion on the signal from each transducer element as it enters the beamformer.

"The first thing that we do is A/D convert the signal, which then is sent to the ASIC that performs the basic beamforming functions," explains Jacques Souquet, senior vice president for beamforming at ATL. "We are now on our fourth generation digital beamformer." The advantage of the digital approach lies in the fact that a digitized signal cannot absorb noise from other parts of the system.

Signals returning from tissue are delayed using a pure digital time delay. Developed into an ASIC, ATL's proprietary digital time delay reportedly replaces the equivalent of four conventional circuit boards. Effectively, this design approach allows capture and processing of all the echoes returning to the scanhead. A beamformer using analog delay lines, according to ATL, would lose or discard almost 50% of the signal bandwidth.

"We readjust the programming of the ASIC on the fly as we receive echoes," says Souquet. "Our electronics are time-delay electronics, and we don't lose any frequency information in our processing approach. We've been able to keep--throughout our whole processing chain--the entire bandwidth coming from the tissue, and therefore the entire signature of the tissue."

ATL's High Definitionimaging systems consist of ASIC-based digital beamformers and high-definition scanheads. The HDI beamformer employs 128 digital channels to drive new scanheads that employ piezoceramic technology and contain as many as 192 elements. "Usually, a scanhead has between 96 and 110 elements. So going to 192 is definitely a big jump," Souquet comments. The piezoceramics are proprietary composite ceramics.

Software rules. Software clearly plays a critical role in ultrasonic imaging of potentially malignant tumors. Souquet believes that the importance of software in the ultrasonic imaging field will continue to grow. "We are witnessing a shift in our industry--or at least within ATL--where software is becoming more and more important in the design of our product. Having been a hardware company, we are slowly becoming a software company." He emphasizes the need to use available software technology as much as possible in ATL's designs. The company's new HDI 3000 fourth-generation ultrasound system, for example, is based on Unix, which simplifies the work of ATL's design engineers.

To take full advantage of the broadband signal captured by a digital beamformer and scanhead, ATL developed what its engineers call the Extended Signal Processing module. This module includes special software and an advanced parallel processing module. The module employs more than two microprocessors, and provides considerable processing power. "Suffice it to say that in the HDI 3000 we process roughly three billion floating point operations per second," remarks Souquet.

Parallel processing reportedly enables ATL's engineering team to significantly reduce the random artificial pattern of overlapping echoes that results from the imaging process. Called speckle noise, this pattern degrades contrast resolution and reduces the ability of ultrasound imaging systems to display tissue boundaries and subtle image variations. Speckle removal involves both software and hardware. "We're doing part of it in a dedicated ASIC which is programmable," Souquet explains, "and the filters are adjusted software-wise. On the receive leg, we process the signal through a bank of various filters. And then the signal is being split through a certain bank of filters pre-programmed depending on the application and the scanhead we're looking at. It's a method called frequency compounding."

Scanheads used in ATL's systems are designed and built by the firm. An in-house group handles ASIC design, and the company uses a mix of Motorola and Intel microprocessors. Various silicon foundries manufacture the ASICs under contract.

Study results. ATL took part in a multicenter international clinical trial of the use of high resolution digital ultrasound as an adjunct to mammography. Fourteen institutions--located in Europe, the United States, and Canada--collaborated in the study. All of the 964 women included had undergone mammography and had been scheduled for biopsy of a breast lesion.

There were 1,021 breast lesions among the women in the study. Data developed during the study demonstrate that HDI two-dimensional and Doppler ultrasonic examination of breast lesions increased the accuracy with which doctors could assess malignancy prior to biopsy.

Basing their decision on the results of this study, an FDA advisory committee panel voted unanimously late last year to recommend approval of the pre-market approval application submitted to the FDA by APL. In April, the FDA accepted the recommendation, and ATL's equipment is now approved as an adjunct to mammography for use in examining lesions one centimeter in diameter or larger. The FDA approval requires the company to offer training in use of the equipment to medical workers. This training will involve either self-study with video and workbooks or seminars. Company spokeswoman Janne Hedberg expects that ATL will establish seven regional sites for such seminars by early fall.