Synchrotron tests for safer breast scans

Despite the fact that early detection and diagnosis can substantially improve women’s chances of surviving breast cancer, the current standard for screening – dual-view digital mammography – leaves as many as ten per cent of malignant tumours undetected. Although computed tomography (CT) scans have been introduced to improve accuracy, there are a number of problematic issues with this technique, including the high dose of radiation required for it to be effective.

In a study published online this week in the early edition of the Proceedings of the National Academy of Sciences (PNAS), a multidisciplinary team from the European Synchrotron Radiation Facility (ESRF), Ludwig-Maximilians-Unversität München’s Munich-Centre for Advanced Photonics Cluster of Excellence (LMU-MAP) and the University of California at Los Angeles (UCLA) revealed a method for producing three-dimensional (3D) scans with a radiation dose 25 times smaller than is usually required.

A powerful algorithm in the software used means that fewer ‘slices’ are required to create a clear 3D image. Lead authors of the study Yunzhe Zhao (UCLA) and Emmanuel Brun (LMU/ESRF) are hopeful that the approach could eventually be used on a routine basis for breast cancer diagnosis.

Two of the paper’s co-authors, Professor Dr Paola Coan and Dr Alberto Bravin, were prepared to field ScienceOmega.com’s questions about the obstacles that the researchers had to overcome to arrive at their discovery and how it will benefit patients, medical studies and other areas of research in the future…

What challenges are presented by the attempt to accurately and safely screen breast tissue?
Mammography is currently the gold standard imaging modality for breast cancer detection. It is used as the primary imaging method in national screening programmes and for the clinical work-up of symptomatic patients. Despite all recent developments, including the introduction of digital detectors, approximately ten per cent of palpable malignant tumours are not visible in mammography. This is mainly due to the limited difference between the properties of glandular and tumour tissue in conventional radiology.

With the aim of improving the sensitivity of the X-ray examination, breast computed tomography (CT) has been introduced in the past years. The benefit of this modality resides in its capability of effectively providing a 3D visualisation of the internal structure of an organ by removing the overlying and underlying anatomical tissue, and, thus, of overcoming the superposition problem of two-dimensional mammography. However, breast CT has not yet been introduced into regular clinical practice because of the excessive X-ray dose necessary for obtaining an image. This is a crucial aspect for highly radiosensitive organs, like the breast, which can be subject to long term biological risks from radiation.

Additionally, for detecting microcalcifications – another important feature that can appear in some types of breast cancer – and in particular their morphology, high spatial resolution is required for visualising the fine structure of different details. Microcalcifications can be ‘benign’ (when isolated and with rounded borders) or ‘malignant’ (when in clusters and with acute edges). Malignant microcalcifications can guide the radiologist in the search for a cancerous lesion in their vicinity.

How does your method tackle these problems?
Recognising these limitations, we went in a new direction. We put together our expertise and made CT scans for early detection of breast cancer possible thanks to the combination of three ingredients: high energy X-rays, a special detection method called ‘phase contrast imaging’ (PCI) and the use of a sophisticated novel mathematical algorithm, known as equally sloped tomography (EST), to reconstruct the CT images from X-ray data.

Tissue is more transparent to high energy X-rays and therefore less of the dose is deposited. PCI, as mastered by the ESRF and LMU-MAP teams, allows images produced with much less X-ray radiation to obtain the same image contrast. The EST method, originally developed at UCLA, requires four times less radiation to achieve the same image quality.

In other words, the new modality simultaneously allows one to reduce the number of images required for obtaining a full CT scan and reduce the number of X-rays needed for each of these images. As a result, we obtained volumetric (3D) high resolution images of the breast at a very low dose. Our results demonstrate the possibility of solving most of the obstacles of conventional X-ray imaging and breast cancer detection outlined above.

How important was the multi-disciplinary aspect of this long-term project?
The synergy of the three teams has been crucial for the success of this research. Without collaboration this result would have not been possible. The multidisciplinary team comprised physicists, radiologists and mathematicians from ESRF (Grenoble, France), LMU MAP and UCLA.

Performing high resolution, low dose imaging requires the disentanglement of several different aspects, calling for expertise in X-ray imaging technology, engineering, image reconstruction and processing, medicine-radiology and so on. The different teams involved in this work have brought their specific and unique expertise in the related fields.

What are the benefits of the new technique and how accurate is it?
The proposed method combines cutting-edge technology in terms of X-ray source, X-ray imaging, CT reconstruction and image processing. The result is the possibility of performing at a spatial resolution comparable to or higher than that used in conventional CT at a very low radiation dose, even lower than conventional dual view mammography.

The fact that PCI allows a better discrimination between healthy breast tissue and breast cancer has been largely proven by previous studies, by our group and others. In particular, our group has recently shown that PCI can make this discrimination in whole breasts. Often researchers make their pioneering studies on small portions of tissues; the same result is not always obvious when translating to whole organs, but this was recently shown in our article.¹

The possibility of also exploiting this in CT – for a 3D investigation – is extremely important in clinical diagnostics, as confirmed by the team of radiologists that has participated in this research. The method makes it possible to overcome the problem of the tissue overlap and to better distinguish normal and abnormal tissue with high spatial resolution. This was achieved at doses which are within the accepted international recommendations, even for highly radiosensitive organs like the breast. Therefore these results significantly reduce one of the major concerns preventing the regular use of CT in breast cancer diagnosis: the biological risk due to the radiation dose.

The method could significantly contribute to clearing up the uncertain results that might occur with the present diagnostic methods, in particular when diagnosis of women younger than 50 is requested. Additionally, it can help in reducing the so-called ‘false positive cases’ (when normal tissue appears abnormal due to lack of a clear visualisation), which are as high as 30 per cent with dual view mammography. Once deployed in hospitals, our method will make CT scans a diagnostic tool to complement dual view mammography and given the low dose, it may become an option for routine breast screening.

How can your work inform further research in this and other areas?
Our method and results are indeed very important not only in breast imaging and breast cancer detection, but also for a 3D investigation of many other organs of the human body.

More importantly, our technique could also have an impact in other scientific applications, besides medicine. In particular it could benefit those fields in which time and dose are important issues and fast high resolution imaging is required. For instance, in the case of in vivo studies with animal models, in the study of dynamic processes (when a certain phenomenon has to be followed by X-rays over time, typical of industrial processes), and in the study of certain biological material which is sensitive to radiation.


¹ ‘High-resolution breast tomography at high energy: a feasibility study of phase contrast imaging on a whole breast’, Sztrókay et al, Physics in Medicine and Biology, May 2012