Pictures of the Future Fall 2008
Early Detection of Diseases – Breast Diagnostics
The Battle against Breast Cancer
Early detection and diagnosis are crucial in the fight against breast cancer. Major advances in imaging technologies are now making possible more precise examinations that place less stress on patients.
Digital mammography accelerates the screening process and delivers high quality images that help to detect cancers early. Breast cancer strikes approximately one out of every eleven women
Margaret M. is relieved. She’s just had a mammogram, a procedure she doesn’t like and also finds uncomfortable—but she knows there’s no getting around it if she wants to protect herself against breast cancer. According to the World Health Organization, some one million women around the globe are diagnosed with breast cancer each year. The National Cancer Institute in Bethesda, Maryland has calculated that there are 211,000 new cases per year in the United States alone, while the Robert-Koch Institute in Berlin reports that 47,500 women are diagnosed with the disease each year in Germany. German statistics also indicate that one out of every 11 women in the country will get breast cancer sometime in her lifetime, with women over the age of 55 facing the highest risk (see Incidence of Breast Cancer by Age).
Nevertheless, the probability of dying of breast cancer is significantly lower today in the Western industrialized nations than it was in the mid-1990s. That’s because sensitive diagnostic procedures such as mammography are making it possible to detect cancers through screenings at an ever-earlier stage, which increases the chances of survival. Mammography, which remains indispensable for early detection, is an imaging procedure in which low-energy (so-called "soft") X-rays are used to produce an image of the breast. Such X-rays yield better images of gland tissue than high-energy radiation.
Because layering in dense breast tissue often makes it difficult to identify tumors, doctors generally take two images at different angles—one from above, and the other on a diagonal from the side of the breast. This makes it possible to capture images of the armpit and pectoral area, which is important because most tumors grow in the top outer quarter of the breast, which faces the armpit.
A major step forward has now been made with new mammography devices such as Siemens’ Mammomat Inspiration (not available for sale in the U.S.), which is equipped with digital detectors. The first of these innovative mammography platforms are already being used in hospitals in Asia and Europe. "Digital mammographic screening has been shown to deliver better results than analog systems when it comes to women who have dense breast tissue," says Dr. Thomas Mertelmeier, Head of Innovation Women’s Health at Siemens Healthcare’s Special Systems business unit. Mertelmeier points to a study conducted at 33 breast cancer centers in the U.S. and Canada, the results of which were published in the New England Journal of Medicine in 2005."
Reducing Radiation Exposure. Unlike conventional mammographs, which use X-ray film, Siemens’ newest mammography system is equipped with a digital detector that more effectively absorbs X-rays. This means the system can deliver better image quality than other systems without increasing radiation dosage. What’s more, the device uses tungsten as the anode material for the X-ray source. This leads to the creation of a spectrum-adjusted X-ray that isn’t absorbed as intensely by the breast, while at the same time allowing a greater number of X-ray quanta to reach the system’s detector. The result is better image quality in digital mammograms. The reduced level of X-ray absorption also makes it possible to lower the mammography radiation dosage, especially for women with dense breast tissue.
Digital mammography offers other advantages in addition to its improved image quality. For instance, it enables images to be viewed on a computer in real time, which opens them up to the world of computer aided detection (CAD) and allows them to be electronically archived and made available within a computer network to any number of participants.
3D Cancer Detection. Digital mammography can be used for both initial screenings and to re-check an existing diagnosis. However, it reaches its limits with women who have very dense breast tissue, because it cannot detect all tumors through layers of tissue and can lead to false-negative diagnoses.
Mertelmeier and his coworkers are therefore working on a new 3D procedure known as breast tomosynthesis (not available for sale in the U.S.), which is being researched to eliminate these disadvantages. With tomosynthesis, the X-ray tube is moved relative to the breast, generating 25 images over the range from +25 to ?25 °, with a separation of 2 ° between any two images.
Image reconstruction is achieved in a manner similar to the technique used in computed tomography, whereby the images serve as a basis for calculating thin slices of the breast. Various breast tissue positions within these slices are then depicted separately, thereby increasing the potential for detecting anomalies.
Three tomosynthesis prototypes are currently being tested at Malmö University Hospital in Sweden, Duke University in North Carolina, and the State University of New York. Swedish breast cancer expert Dr. Ingvar Andersson, who is testing the system in Malmö, says that he is very happy with its preliminary results to date.
The New England Journal of Medicine reports that the risk of breast cancer is about five times greater for women with dense breasts than for those women with non-dense tissue. And while mammography remains the method of choice for breast cancer screening, clinical studies have indicated that performing an additional ultrasound exam may in some cases significantly increase cancer detection in dense breast tissue.
According to a 1998 study by T.M. Kolb, the detection rate for non-palpable, invasive cancers increased by 42 % in women with dense breasts when their mammography was followed by an ultrasound examination. That’s why Malmö University Hospital’s Dr. Andersson would like ultrasound to be added to the standard breast exam protocol for women with dense breast tissue.
Jacqueline Bailey, marketing manager at Siemens Healthcare’s Ultrasound Business Unit in Mountain View, California, agrees. In North America and Europe, for instance, about two in five women, and in Asia three in five women, have dense breast tissue. "For these women, ultrasound may provide additional diagnostic information," says Bailey. Ultrasound is a non-invasive imaging procedure that is free of ionizing radiation and that women usually find to be more comfortable than mammography since it does not require breast compression.
Automated Imaging. Conventional ultrasound requires a hand-held transducer to manually scan the breast. This technique, however, delivers only a partial view of the breast from a limited number of positions, depending on how the user moves the transducer over the breast. In addition, it can be time-consuming. This is why Siemens set out to innovate this examination by developing a new automated ultrasound system designed specifically for breast scanning: the Acuson S2000 Automated Breast Volume Scanner (ABVS). This system quickly and painlessly surveys and acquires full-field ultrasound views of the breast. In addition, it provides efficient and comprehensive analysis of the 3D data and facilitates easy, semi-automated reporting.
Breast cancer detection (from L) can include digital mammography, a biopsy, computer aided detection (CAD), ultrasound based on Automated Breast Volume Scanning (ABVS), and fusion of MRI & PET data
from left: syngo MammoCAD marks a suspicious-looking lesion; ABVS ultrasound scanner reveals breast cyst; Fusion of sequentially-acquired MR and PET images reveals a two-centimeter lesion
The system consists of a column stand and arm assembly that holds a 15 × 15 cm² transducer pod specially designed for breast ultrasound. Placed on the breast, it automatically performs the scan, creating 250 to 400 single images. Data acquisition takes only about 60 to 90 seconds, while the entire examination requires anywhere from four to 10 minutes, making it significantly faster than hand-held ultrasound.
Once the data has been acquired, it is sent to an offline workstation for analysis and reporting. The volume data can be viewed in three different planes—as transverse, sagittal, and coronal sections. The latter, which allows the physician to review breast images along their most anatomically natural direction, runs from nipple to chest wall, and could not previously be represented by conventional ultrasound examinations. The scanner was rolled out for the media in the United States and Europe in fall 2008 and is expected to be available worldwide at the end of 2008.
Ultrasound is the standard procedure for evaluating suspicious abnormalities following a mammogram, analyzing lesions, and guiding biopsies. New ultrasound breast imaging technologies make it possible for physicians to gain greater insight into tissue pathologies during diagnostic exams.
One such innovation is eSie Touch elasticity imaging, a technology available on Siemens ultrasound systems. Elasticity imaging displays the mechanical properties exhibited by tissue. Here, the sonographer gently presses the transducer onto the breast, while the ultrasound system calculates and depicts the stiffness of a lesion. Clinical experience has shown that harder and less mobile lesions are more likely to be malignant.
New Perspective on Breast Imaging?
Siemens is involved in an EU-funded project launched in the summer of 2008 with the universities of Erlangen, Germany, Leuven, Belgium, and Rotterdam, Netherlands. The goal of the Erlangen-based project is to develop a specialized device that will allow the breast to be examined using computer tomography (CT). Project researchers are hoping that CT will eliminate the problem of tissue overlapping in layered images. Up until now, conventional CT has not been used for breast cancer screenings because the associated radiation dosage was considered too high. With the new procedure, however, the patient’s breast is passed through an opening in the examination table. An X-ray tube with a detector rotates underneath the table, generating a complete 3D volume image. Plans call for a reduction of the radiation dosage down to mammography levels, while still achieving nearly the same image resolution. If these objectives can be met, the technique could be developed into a standard method in coming years.
High Specificity. Ongoing research, which is being conducted by Richard G. Barr, a professor of radiology at Northeastern Ohio University’s College of Medicine and a radiologist at Southwoods X-ray and MRI in Youngstown, has shown that elasticity imaging offers high specificity.
Dr. Barr used Siemens’ real-time, eSieTouch elasticity imaging technology to study 166 lesions identified and scheduled for biopsy in 99 patients. Ultrasound-guided biopsies were performed on 80 patients with 123 lesions. Biopsy showed that elasticity imaging correctly identified all 17 malignant lesions and 105 of 106 benign lesions, resulting in a sensitivity of 100 % and a specificity of 99 %. The results of his study are now being verified in several studies in Europe and the U.S.
The Role of MRI. Mammography and ultrasound are not the only technologies available for breast cancer screening and diagnosis. Physicians may also opt for magnetic resonance imaging (MRI), which requires no exposure to X-rays.
The American Cancer Society recommends that women at risk of getting breast cancer due to their genetic history (family history of breast cancer, etc.) should undergo a breast MRI exam every time they go for their annual mammography. This recommendation is based on a 2004 study published in the New England Journal of Medicine, which revealed that MRI can detect tumors that do not show up on a mammogram.
"MRI is ideal in terms of detecting and depicting new blood vessels," says Birgit Hasselberg, an oncology product manager at Siemens Healthcare’s Magnetic Resonance division. "Because tumors need new blood vessels in order to grow, the presence of such vessels can be taken as an indication of a tumor in a very early stage of development," she adds.
In addition to its role in screening, magnetic resonance imaging can also be used in planning surgical operations, monitoring tumor response to treatment over time, and post-operative assessment. Depending on how advanced it is, breast cancer may be limited to the breast itself or have spread to lymph nodes, in which case metastases are possible.
Determining the stage of the disease is essential when selecting the proper treatment, which in turn can have a major impact on the patient’s chances of survival. That’s why it’s so crucial to detect the primary tumor at the earliest possible stage and then remove it completely.
The Road to Universal Screening
The two houses of parliament in Germany—the Bundestag and the Bundesrat—passed legislation in 2002 that would allow all female German citizens between the ages of 50 and 69 to obtain free mammography screenings in a practice similar to that already established in Scandinavia. Later, health insurance companies and the German medical association established a cooperative mammography project, which set up five reference centers in 2005.
Several of the centers help to ensure nationwide coverage by sending out mobile examination stations in the form of large truck trailers (Mammotrailers). The vehicles contain a waiting area, an examination room with mammography technology, and a small office. Siemens and an automotive supply company built 28 of these mobile mammography stations for the Mammotrailer pilot project, which utilized mammography units that store their data on X-ray film. Preparations are now under way to deliver new Mammotrailers that will be equipped with digital mammography devices (Mammomat Novation and Inspiration) capable of taking measurements with digital detectors.
Mobile mammography stations equipped with Siemens technology can also be found in Denmark, Poland, and Georgia. In Germany, the devices are normally operated by medical technicians, who only take measurements. They then save the data in encrypted form in a storage medium that is delivered by courier to a reference center, where a radiologist evaluates it. The mobile mammography stations travel all year round, stopping in defined areas for as much as 50 days, where they cover a radius of several kilometers. This service has led to a high level of acceptance and thus participation, with some 64 % of all women contacted by the mammography cooperative having undergone a screening examination.
Magnetic resonance delivers images of the highest resolution that show the precise dimensions and shape of a tumor in its early stages. Because of its precision, the technology is ideal for assisting with the planning of operations and helps to ensure that the entire tumor is detected and removed, thus minimizing the chances of recurrence and helping to prevent spreading. If the cancer has already metastasized, magnetic resonance imaging can be used to take a whole-body scan and to identify the locations of distant tumors.
In the near future, magnetic resonance technology will be used in breast spectroscopy devices now being refined by Siemens Healthcare in Erlangen, Germany. The instruments are now being tested in a multi-center study. Magnetic resonance spectroscopy imaging (MRSI) is a non-invasive procedure that can detect metabolic products and biochemical changes in cells. Here, Siemens’ syngo GRACE software reports on the concentrations of the body’s own metabolites, such as choline, in cells. This information enables doctors to draw conclusions regarding cell malignancy. The technique is ideal for monitoring the effectiveness of medication during treatment, as it can document treatment success or lack thereof on the basis of either rising or falling choline concentrations.
An alternative procedure is the fusion of sequentially required positron emission tomography (PET) and MR images in which the PET scan depicts glucose metabolism in cells, while the MR image localizes the tumor.
Because PET normally cannot function in the presence of magnetic fields, the two procedures are still performed separately in most medical centers. However, initial clinical results at the New York University School of Medicine show that combining PET scans with standard MRI breast scans improves the quality of diagnoses.
New ultrasound imaging technology is improving doctors’ ability to evaluate tissue. Elastography, for example, can be used to assess whether a lesion is benign or malignant
Identifying Lesions with Algorithms. Computer aided detection (CAD) programs, such as syngo MammoCAD (not available for sale in the U.S.) from Siemens, are helping radiologists detect breast cancer as early as possible with unprecedented accuracy. CAD software analyzes digital mammograms and marks suspicious areas for review by clinicians. During routine clinical care, doctors may have to analyze dozens of patients per hour, leaving little room for error.
"On average, one malignant lesion is found for every 200 patients who undergo a breast cancer screening," says Jonathan Stoeckel, managing director of Siemens Computer-Aided Diagnosis Ltd. "Without CAD, it’s quite possible for a doctor to miss something."
At the same time, it’s not at all helpful if CAD software sees too much—in other words, places false positive marks on areas without any abnormalities. syngo MammoCAD has a low rate of false positive marks, with approximately 40 % of normal cases having no marks at all. However, as CAD algorithms continue to advance, performance is expected to further improve. "The ideal situation, of course, would be if the system identified and marked only malignant lesions," says Stoeckel.
syngo MammoCAD identifies masses and clusters of micro-calcifications that warrant a second look from a clinician. Masses are visible in the images as areas of higher density and micro-calcification clusters are visible as areas with white dots representing individual calcifications.
Data that Supports Accurate Decisions. syngo MammoCAD is being continuously enhanced not only with regard to algorithm performance, but also with regard to the scope of clinical decision support. The next stage of software development, for example, will provide doctors with a description of each marking with regard to tumor shape, margins and density.
Radiologists already describe lesions in accordance with the BI-RADS Atlas (Breast Imaging Reporting and Data System Atlas) standard that is used for diagnoses. In the future, CAD software will also be able to support this task. "CAD is thus being transformed from computer aided detection to computer aided description," says Stoeckel, who is already working on the next stage of software development.
A first step in this direction has already taken place. Radiologists are now able to use CAD to sort cases according to tissue density, which enables them to view and address the most critical ones first. In the future, this decision-support system will work with the Remind platform (see Pictures of the Future, Spring 2008, Remind) and combine artificial intelligence procedures with huge databases and tremendous computing power.
The development of computer aided detection software for breast MRIs is moving in the same direction. "Breast MR CAD will inform users in their own language, meaning the BI-RADS Atlas standard, regarding why it marked a particular area," says Arun Krishnan, head of CAD Research at Siemens IKM CAD & Knowledge Solutions in Malvern, Pennsylvania. Plans also call for additional data such as digital patient records to be incorporated into the system further down the road. "Our overriding goal is to offer patients the best possible solution," Krishnan explains, "with an emphasis on avoiding unnecessary biopsies." Breast MR CAD is currently limited to the realm of pure research at Siemens.
When Margaret M. gets her next breast cancer screening test, 3D tomosynthesis will have replaced digital mammography. To ensure no lesions are overlooked, she will also undergo an ultrasound examination with the Automated Breast Volume Scanner.
Increasingly sophisticated imaging technology is now making it possible to identify tumors at earlier stages, while modalities such as MRI and PET-MR image fusion are reducing the number of unnecessary biopsies. If a tumor is discovered someday in Margaret M’s breast, advanced CAD software should be able to generate a personalized treatment proposal based on a range of measurement data. And that means that she would have a much better chance of surviving to an advanced age than did her mother, who died of breast cancer when she was still young.
Michael Lang