Scientists have developed a way to produce three-dimensional X-ray images of the breast at a radiation dose that is lower than the 2D radiography methods used in clinics today. The new method enables the production of 3D diagnostic computed tomography (CT) images with a spatial resolution 2-3 times higher than present hospital scanners, but with a radiation dose that is about 25 times lower. This breakthrough has the potential to overcome the main obstacle limiting conventional CT imaging of the breast: the high radio-sensitivity of the breast glandular tissue. Synchrotron X-rays at beamline ID17, the medical station of the ESRF, have been used to test the technique which, once deployed in hospitals, will make CT scans a diagnostic tool to complement dual view mammography.

The multidisciplinary team comprised physicists, radiologists and mathematicians from the European Synchrotron Radiation Facility (ESRF, Grenoble, France), the Ludwig Maximilians University in Munich (LMU, Cluster of Excellence MAP) and the University of California at Los Angeles (UCLA). The first authors are Yunzhe Zhao of UCLA and Emmanuel Brun of the LMU/ESRF.

Early detection contributes to an improved prognosis and results in reduced breast cancer mortality. The breast cancer screening method typically used today is ‘dual-view digital mammography’. The limitation is that it only provides two images of the breast tissue, which can explain why 10 percent to 20 percent of breast tumours are not detectable on mammograms. Mammograms can also sometimes appear abnormal, when no breast cancers are actually present.

Computed tomography (CT), an X-ray technique that allows a precise 3D visualisation of the human body organs, cannot be routinely used for breast cancer diagnosis because the risk of long-term effects in radiosensitive organs like the breast is considered too high.

Recognising these limitations, scientists have tackled the problem using a new approach. They combined three ingredients that together should now make CT scans for early detection of breast cancer become possible. These ingredients are: high energy X-rays, a special detection method called ‘phase contrast imaging’ and the use of a sophisticated novel mathematical algorithm, known as ‘equally sloped tomography’ (EST), to reconstruct the CT images from X-ray data. Tissues are more transparent to high energy X-rays and therefore less dose is deposited (a factor of 6 in radiation dose reduction). Phase contrast imaging, mastered by the ESRF and the LMU-MAP teams, allows the production of images using fewer X-rays to obtain the same image contrast. Finally, the EST method, originally developed by researchers at UCLA, needs 4 times less radiation to obtain the same image quality.

The team X-rayed a human breast at multiple different angles using phase contrast tomography and applied the EST algorithm to 512 images to produce higher resolution 3-D images of the organ than ever before and at a lower dose than a mammogram.

In a blind evaluation, five independent radiologists from the LMU ranked the generated images as having the highest sharpness, contrast, and overall image quality compared to 3-D images of breast tissue created through other standard methods.

‘This new technique can open up the doors to the clinical use of computed tomography in the breast diagnosis, which would be a powerful tool to fight even better and earlier against breast cancer’, says Prof. Maximilian Reiser, Director of the Radiology Department of the LMU, which provided the medical expertise for this research. ‘This result has been obtained thanks to the synergy of the expertise by researchers from very different disciplines. These high-quality X-ray CT images at high energies are the result of a 10-year effort at the ESRF’ says Alberto Bravin, head of the ESRF medical research laboratory who led the team in Grenoble. ‘After dramatically reducing the dose delivered during the examination of the breast, our next objective is to develop this technique in the early visualisation of other human diseases and to work towards its clinical implementation.’ adds Paola Coan, Professor of X-ray imaging at the LMU and member of the Munich-Centre for Advanced Photonics (MAP), who led the group from Munich.

Monitoring the effectiveness of the HPV vaccine in Canada requires that data from multiple registries and other data sources be combined. Linking registries can be problematic, however, since they are often managed by unrelated organisations. Privacy legislation may also restrict the sharing of data for such linkages. To address these challenges, Dr. Khaled El Emam and his team at the CHEO Research Institute have developed a secure protocol that allows the linking of individual patient records without revealing personal information.
According to Dr. El Emam, previous protocols were not secure or did not protect privacy; this new evidence-based protocol, however, is the strongest on record. It can be generalised for use in monitoring other conditions or diseases, or vaccination programs.
‘There is a need to do long-term evaluations of vaccines, and to monitor vaccination rates and how they vary by individual and family characteristics. Access to data to perform such surveillance is often challenging because of legitimate privacy concerns. Our protocol addresses these concerns directly and facilitates rapid data sharing,’ explained Dr. El Emam.
HPV, or the human papillomavirus, is one of the most prevalent sexually transmitted viral infections in the world, causing symptoms that range from genital warts to increased risk of cervical cancer. An effective preventative quadrivalent vaccine has been available in Canada since 2007 (and a second, bivalent vaccine was approved for use in 2010) and is regularly administered to girls through publicly funded school-based programs. The vaccine can potentially reduce health care costs and HPV-related illnesses and death, but the long-term effectiveness of the vaccine is not yet known. Further research is required to gauge the vaccine’s lasting impact on health and to inform policy decisions concerning the allocation of health resources.
The new protocol uses a number of cryptographic techniques, including a commutative hash function and homomorphic cryptosystem. The secure computation allows registries to match records on identifiers such as SIN, health card number and date of birth without revealing these values to anyone, and then perform analytics on the linked data without that linked data being disclosed. The protocol provides end-to-end privacy protection for surveillance programs and eliminates many concerns about sharing data.
‘We set out to assess the impact of the HPV vaccine by creating a secure protocol to link simulated databases on cancer, cervical screening, health care services and immunisation. Such linkage can only be done in an environment that is responsive to patient privacy concerns,’ explained Dr. El Emam. ‘The protocol we created would allow any public health unit to link databases from multiple sources and compute relevant statistics from linked data without revealing personal information, and hence, still provide strong patient privacy guarantees.’ Children’s Hospital of Eastern Ontario Research Institute

A study showed that some doctors, particularly surgeons, are not explaining the risk of specific outcomes that matter most to patients. Overlooked risks that led to a legal claim or complaint included chronic pain, sexual dysfunction, visual or hearing loss, and the need for re-operation.

Lead author Dr Marie Bismark from the University of Melbourne School of Population Health said the study revealed that doctors may routinely underestimate the importance patients place on understanding certain risks in advance of treatment.

‘Increasingly, doctors are expected to advise and empower patients to make rational choices by sharing information that may affect treatment decisions, including risks of adverse outcomes,’ she said.

‘However, doctors, especially surgeons, are often unsure which clinical risks they should disclose and discuss with patients before treatment and this is reflected in this study.’

The authors found that the most common justifications doctors gave for not telling patients about particular risks before treatment were that they considered such risks too rare to warrant discussion, or that the specific risk was covered by a more general risk that was discussed.

‘It is not necessary, or helpful, for doctors to provide a laundry list of all possible risks. Instead, doctors should focus on discussing those risks which are likely to matter most to the patient before them,’ she said.

From a sample of nearly 10,000 patient complaints and malpractice claims from Australia between 2001 and 2008, researchers identified 481 disputes involving alleged deficiencies in obtaining informed consent.

The authors found that 45 (9%) of the cases studied were disputed duty cases

Leading clinicians and health researchers from across Europe say much greater emphasis must be placed on the scientific evidence for the effectiveness of treatments and other healthcare interventions to ensure patients receive the best care available. The call is contained in a Science Policy Briefing published by the European Medical Research Councils, which also made ten key recommendations on how to improve the quality of research and healthcare in Europe. The briefing,

University of Michigan heart researchers are shedding light on a new method for steadying an abnormal heart rhythm.
Irregular heart rhythms, or arrhythmias, set the stage for a common, debilitating disorder called atrial fibrillation that puts adults as young as age 40 at risk for fatigue, fainting, cardiac arrest, and even death.
Medications can help, but doctors also use catheter ablation in which electrical impulses are delivered to a region of the heart to disrupt the arrhythmia.
However, half of patients require more than one ablation to see results. In a laboratory study, the U-M used photodynamic therapy, a technique long used in cancer research, to disrupt the specific cells causing the arrhythmia.
The study suggests cell-specific cardiac ablation could help patients avoid complications, and get closer to an arrhythmia-free life without having to undergo repeat hospital visits.
Chemists in the U-M Department of Chemistry and electrophysiologists at the U-M Center for Arrhythmia Research collaborated on the study that will require further examination before it is available in the hospital setting.
‘This cell-selective therapy may represent an innovative concept to overcome some of the current limitations of cardiac ablation,’ says lead study author Uma Mahesh Avula, M.D., research fellow at the U-M Center for Arrhythmia Research.
The heart consists of different types of cells such as myocytes, fibroblast, adiopocytes and purkinje fibres, which are all needed for normal cardiac activity.
The new study is the first of its kind to use photodynamic therapy and nanotechnology to ablate only the cardiac myocytes responsible for arrhythmias. In current ablative techniques, all cardiac cells receive ablative energy, which can lead to complications such as puncturing the heart muscle, bleeding or stroke.
‘Current ablation techniques are severely limited by its non-specific nature of cellular damage. Besides this lack of cellular discrimination markedly increases the required energy amounts and prolongs procedure times, all of which reduces overall ablation results,’ Avula says.
Catheter ablation has emerged as an important treatment option that requires careful assessment, planning and execution for optimal success rates. Advances over the past 20 years have made the treatment safer, but it remains highly complex.
‘Approaches that could simplify and shorten the procedure may contribute to more patients being treated,’ Avula says.
Rather than radiofrequency energy, the most common type used in cardiac ablation, the U-M team introduces the use of PDT in cardiac electrophysiology to target specific cell types. Targeted PDT, which was pioneered in the labs of study senior author U-M chemist and engineer Raoul Kopelman, Ph.D., is extensively used in cancer research for selectively killing cancerous cells.
The disruption induced by PDT is confined to cells that have been photosensitised, while adjacent non-photosensitised cells are unaffected. The U-M has applied for a patent for this technology.
‘We think this approach will decrease the extent of unwanted cell injury, inflammation, and ablation-related tissue damage, and pave a way for the development of more effective therapies for cardiac arrhythmias,’ says study senior author J