X-ray elastography: a novel approach to breast imaging

The mechanical properties of tissue, such as stiffness, have long been known to be an important indicator of the health of tissue. Indeed, manual palpation is used regularly by clinicians as part of routine diagnostic procedures. A range of techniques have been developed in order to obtain images, both in two and three dimensions, of tissue stiffness. This approach, known as elastography, is significantly more powerful than manual palpation as the clinician is able to visualise the location, and relative stiffness, of tissue within the body.

Existing elastography techniques are based on ultrasonoghraphic imaging (i.e. ultrasound, US), magnetic resonance imaging (MRI) and optical imaging. US based elastography has developed to the point where it is able to be used as part of a routine breast cancer diagnosis protocols. One of the problems with these established techniques is that their ability to resolve small features, such as small tumours, degrades as these tumours are located within the body. For example, optical techniques are able to resolve features as small as 0.02mm, however, only if they are located within about 1mm of the skin. Tumours over 0.1mm in size can be detected using US elastography if they are located less than 10cm from the skin surface, and so on.

We propose to make use of a recently developed X-ray imaging technique, known as phase imaging, which provides images of biological tissue which are much clearer than conventional X-ray imaging. Using this technique we believe it will be possible to obtain images of tissue stiffness, resolving features as small as 0.02mm, located deep within the body, thus breaking the limitation of existing elastography techniques.

Although applicable to a range of applications, we will apply this technique to breast cancer imaging. If successful, the technique could be applied in screening, diagnosis and treatment of breast cancer. In particular, it could be integrated into a form of three-dimensional mammography known as tomosynthesis, giving the radiologist an additional form of contrast upon which to make their diagnosis. Once a suspicious lesion has been detected at the screening stage, this technique could be used in follow up imaging, again to provide the radiologist with an additional form of contrast upon which to make their diagnosis. Finally, if surgery is required, it may be possible to use this technique to check that the tumour has been completely removed at the time of surgery, rather than requiring a patient to return for follow-up surgery to remove any remaining tumour.

The proposal seeks to develop new technologies and techniques for application in breast cancer screening and research. The beneficiaries of this research will thus be broad and numerous as outlined below. I would like to emphasise that the proposed technique is foundational and has great potential to impact the fields of medicine and biology outside breast cancer.

Knowledge of breast tumour biology: The mechanical properties of tissues and cells are important in determining tissue health. Mechanical properties are also an important factor in metastasis, the act of cancer spreading to other parts of the body. The ability to image the mechanical properties of entire sections of excised tissue with resolution approaching the cellular scale will provide new knowledge that will guide research in tumour biology. It is hoped that the developed technique will become commonly used amongst the tumour biology community as a research tool. The ideal outcome of this work is that X-ray phase elastography goes beyond answering current questions, but provides the means of posing new research questions.

Reduced breast cancer related physical and psychological trauma in society: A primary goal of this research is to demonstrate the feasibility of intra-operative breast tumour margin assessment. An immediate impact of this achievement would be a reduction in the number of patients required to undergo re-excision due to tumours being only partially removed, which currently accounts for 20% of patients undergoing breast conserving surgery. Avoiding a second surgery in a large proportion of these patients will lead to a significant reduction in both physical and psychological trauma associated with such occurrences. If, as is planned, this technique can be extended to breast screening, it is anticipated that a reduction in false positives, i.e., patients given an initially incorrect positive diagnosis, will be achieved. This will save a significant emotional trauma associated with false positive diagnoses and the necessary follow up medical procedures.

Cost savings in the NHS: Reducing the number of re-excision surgeries will generate an immediate cost saving in the NHS. A reduction in false positives will lead to cost savings by reduced need for follow up imaging such as ultrasound and biopsies.

Economic development of UK companies: Once demonstrated, this technique will be able to be rapidly deployed in commercial imaging systems due to its high compatibility with existing technologies. The phase contrast imaging group is ideally placed to facilitate this through its long standing collaboration with Nikon Metrology UK. Beyond this, however, once demonstrated, the technique would be able to be licensed for use in existing X-ray CT and micro-CT systems throughout the world as an accessory.

Training of scientists: This project will enable, in the first instance, a PhD student and research assistant to learn the skills required to work in the field of elasticity imaging. Whilst well established using imaging modalities such as MRI and ultrasound, this technique is yet to be successfully demonstrated using X-rays. Through collaboration with project partners, it is anticipated that both the PhD student and research associate will develop the necessary understanding in biology, medicine and X-ray phase imaging. This knowledge will be readily transferrable to other, related, techniques.

Leveraging existing expertise in medical image computing: This imaging technique will require the use of computer algorithms to map the displacement of tissue resulting from the application of a compressive load. Whilst the PI has experience in this, it is recognised that a leading medical image computing group resides with the PI's own department. It is thus proposed that the wealth of knowledge and resources in the field of medical image registration be applied in a new application area, thus deriving additional value from existing tools.