Since the late 1990s, emergency radiology has become one of the fastest developing areas of medicine. It is now commonplace not only in Europe, the US and Japan but also in major urban centres of several developing countries.
The appropriate use of emergency radiology expedites patient care, prevents unnecessary hospital admissions and emergency surgery and therefore reduces costs.

Sub-specialty of radiology
Formally, emergency radiology is a relatively new sub-specialty of radiology. It is defined by the imaging and subsequent management of trauma patients, as well as those who are acutely ill. In effect, it is associated with real-time diagnostic imaging and online interpretation of data, which are conducted and completed in the ED setting itself. Emergency radiologists, on their part, need to be available and provide interpretations of imaging around the clock, including all off-hours shifts.

Professional societies set up very recently
The American Society of Emergency Radiology (ASER) was founded in 1988, with a mission to ‘advance the quality of diagnosis and treatment of acutely ill or injured patients by means of medical imaging and to enhance teaching and research in emergency radiology.’ ASER publishes the journal Emergency Radiology’ and has more than 700 members, both from the US and overseas.
The European Society of Emergency Radiology (ESER) was established in 2011, or over a decade later than its US counterpart. Based in Vienna, ESER seeks to foster education and training in emergency radiology, and collaborate both with the ASER and the British Society of Emergency Radiology (BSER), which was set up in 2014.

Radiography and fluoroscopy: limitations
Traditionally, ED imaging consisted of radiography and fluoroscopy. The procedure began with chest, abdominal and skeletal radiographs, accompanied sometimes by intravenous urograms and barium examinations. Emergency angiography was used in patients with central nervous system or vascular conditions.
Many trauma patients were, however, unable to have completion of imaging examinations in the ED, and several presenting diagnostic uncertainty were admitted to the hospital for fluoroscopic or angiographic procedures.

CT impact dramatic
Emergency medicine practice was revolutionized in the 1990s by the increase in availability of ultrasound, MRI and above all, CT. In spite of some lingering concerns, the speed of CT dramatically altered the equation in emergency radiology. A whole-body trauma CT requires just two minutes, providing information about all major injuries to the head, spine, thorax, abdomen and pelvis and increasing the probability of survival for trauma patients.
These new imaging modalities effectively served to bridge emergency medicine and diagnosis. Dramatic improvements in image quality and acquisition times have since enhanced the role of radiology in diagnosis, and as a bridge to minimally invasive procedures.

Shortening TAT
Such developments, in turn, catalysed an increase in expectations, with emergency physicians demanding quick availability of all imaging modalities, high-quality imaging examinations, real-time 3D post-processing and round-the-clock service – in effect, shortened turn-around times (TAT).
It has for long been a maxim that care provided to a trauma patient in the first few hours can be critical in terms of predicting longer-term recovery and that good trauma care involves getting the patient to the right place at the right time for the right treatment.
Professional societies have anchored such thinking. For example, guidelines from the Royal College of Radiology in Britain recognize that in the overall management of the severely injured patient, ‘diagnostic and therapeutic radiology plays a pivotal role’, although it is but a small part of ‘the whole management process.’

CT poses logistical challenges
Accompanying the increased emphasis on TAT and demands from physicians, emergency radiology facilities began to steadily reduce conventional radiography or replace it with digital X-ray. Instead, CT began to be moved to emergency departments. For example, the Royal College of Radiology guidelines mentioned above specify that CT should be adjacent to, or in, the emergency room (Standard 3) and that digital radiography should be available in the emergency room (Standard 4).
The move to relocate CT has also been driven by a need to reverse some of the major problems associated with scanners in a hospital-based trauma setting – the result of a combination of high technology and poor logistics.
Logistical problems centred upon the need for optimal location of a scanner and the capacity to receive severely injured patients within a very short period of time. This, in turn, required the availability of sufficient radiographers, a seasoned transfer procedure and resuscitation teams to be familiar with a CT environment and ready to accompany the patient during the scan.
Most traditional’ hospitals, dating back to the radiography and fluoroscopy era, were unable to cope with the dramatic changes which CT brought – above all in speed and imaging data sensitivity. This resulted in serious bottlenecks in workflow, which impacted adversely on patient outcomes.
Such shortcomings were enhanced by spikes in the volume of patient visits – e.g. during weekends and over holidays – when accident rates are far higher.

New standards for emergency radiology
To help CT relocate and become more efficient, emergency radiology facilities are being subject to exacting, new standards.
For example, the University of Amsterdam’s Academic Medical Centre (AMC) has been designed to enhance workflow efficiency and prevent dangers in the transfer of critically ill patients, while avoiding or reducing delays for non-emergency patients with scheduled appointments in the radiology department. By enabling proper equipment, transfer and support, AMC has sought to address concerns in emergency departments that, in spite of its benefits, CT might be a dangerous place for the critically ill. This was largely due to perceived limits in ventilation, resuscitation and monitoring during scanning.
One of the most visible innovations at the AMC is a sliding CT gantry on rails which serves two emergency rooms. A radiation-shielding wall closes behind the gantry, allowing the scan to be performed feet-first so IV-lines and monitors do not have to be re-positioned.
In terms of staffing, emergency radiologists at AMC are supported by a dedicated anesthesiologist who initiates ventilation, surgical residents or nurses to insert chest tubes and and radiology residents to help interpret the imaging data. This team interfaces with the trauma surgeon.

Staffing issues
Non-physician staffing is also crucial to an efficient emergency radiology facility. These range from technicians, supervisors and ED managers to receptionists, schedulers as well as ambulance personnel. State-of-the-art facilities strive to make such staff aware of the unique workflow and requirements of emergency imaging. For example, technicians need to have the skills to use different modalities and image multiple body parts. Beyond this, non-physician staff need also to be well versed in other, point-of-care medical equipment and manage a diverse range of patients – from the acutely ill to the pregnant, from children to the elderly.
A key role is also played by IT support staff, who need to be on call round-the-clock. Given the pressures to reduce TAT, they need to be well versed in RIS/PACS solutions and their suite of integrated tools, such as speech-to-text, 3D visualization, and others. More recently, IT professionals have also played a major role in data mining, in order to identify workflow bottlenecks and special situations.

Decision support tools
Another related and fast-emerging sphere consists of decision support tools, which communicate the clinical presentation, physical examination, and laboratory tests. They also confirm imaging appropriateness and selection of the optimal examination protocol.
Decision support is also seen as a means to reduce common causes of superfluous radiation in ED patients, for example, by avoiding repeat CTs (e.g. in referring hospitals). Indeed, one of the most closely-watched debates about emergency radiology concerns CT.

CT versus the rest
CT has undoubtedly been the centrepiece of the emergency radiology revolution. In 2016, a prospective study in Radiology’ showed that CT influenced the leading diagnoses in 25percent-50percent of patients and admission decisions in 20percent-25percent of patients.
Nevertheless, radiography continues to remain the most widely used imaging modality. In the US (for which data is available from a study in the American Journal of Roentgenology’ ), CT was used in 268 of 1,000 ED visits in 2012, compared to 76 for ultrasound, 64 for MRI, and 510 for X-ray.
The study, published in August 2014, also drew some other notable conclusions.
CT use in the ED peaked in 2005, while this happened two years later for MRI. Compared to 1993, CT use grew 457percent by 2005 and then declined by 49percent to 2012. For MRI, growth from 1993 to its 2007 peak was sharper, at 1,750percent, while the fall between 2007 and 2012 was 23percent, half the rate of CT. This was, nevertheless, from a much smaller user base, and as mentioned above, MRI use in the ED is outstripped more than 4-to-1 by CT (64 to 268 per 1,000 visits).
Ultrasound, on the other hand, has shown a steady but less remarkable increase in ED use between 1993 and 2012, by just 35percent. Conversely, although X-ray was used in over half ED visits in 2012, it has fallen steadily since 1993, by 26percent.

REACT-2: reality check for CT
Future trends in emergency radiology are likely to be heavily influenced by a randomized controlled trial trial at four hospitals in the Netherlands and one in Switzerland. Known as REACT-2, the trial sought to determine the effect of total-body CT scanning compared with standard work-up on patients with trauma and compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury.
The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury.
Between April 2011 and Jan 1, 2014, the trial assessed 5,475 eligible patients and randomly assigned 1,403, 702 to immediate total-body CT scanning and 701 to the standard work-up. A total of 541 patients in the immediate total-body CT scanning group and 542 in the standard work-up group were included in the primary analysis. The study found that in-hospital mortality did not differ between groups.
As The Lancet’ reported on August 13, 2016, ‘Diagnosing patients with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT.’

More MR?
Alongside such selection, it is also likely that there is an increase in demand for MR scanning in the ED, whose decline from its peak has been half the rate of CT (in the American Journal of Roentgenology’ study mentioned previously).
So far, MR is not indicated in an acute trauma care setting. In Britain, for example, Royal College of Radiology trauma radiology guidelines specify that MRI can be available in a different building. However, it states that ‘protocols should be in place for the transfer of critically injured patients if further management is dependent on MRI in the first 12 hours.’
Some of the benefits of MRI versus CT include acute musculoskeletal injuries, and in imaging of acute abdominal conditions in pregnant women and children.

Dynamic contrast-enhanced magnetic resonance (DCE-MRI) is a functional imaging technique. It consists of MRI scans coupled to the injection of a contrast agent. The latter leads to a decrease in relaxation time and provides extremely detailed characteristics of the micro-circulation of blood through tissue.
DCE-MRI assessments typically use the characteristics of signal intensity (SI) and time-intensity curves (TIC) regarding regions of interest (ROI). Early DCE-MRI efforts assumed a linear relationship between signal enhancement and contrast uptake. However, given that signal enhancement depends to a very great degree on intrinsic tissue and acquisition parameters, more complex models have been developed to control the effect of tissue characteristics such as the pre-contrast longitudinal relaxation time and the longitudinal or transverse relaxivities of the contrast agent.

Two-phased process
DCE-MRI is a two-phased process. Typically, at first, a T1-weighted MRI scan is conducted. This is followed by injection of the contrast agent, and then repeated acquisition of T1-weighted fast spoiled gradient-echo MRI sequences to obtain measurements of signal enhancement as a function of time.
The contrast agents are usually based on gadolinium and include gadoterate meglumine (Gd-DOTA), gadobutrol (Gd-BT-DO3A) gadoteriol and albumin-labelled Gd-DTPA.

Image acquisition and voxel comparison
Typically, 3D image sets are obtained sequentially every few seconds for up to 5-10 minutes. Shorter intervals allow for detection of early enhancement, although many researchers consider 10 seconds to be good enough. Longer intervals than this typically makes it tougher to identify early enhancement.
At the moment, the debate about the upper limit for intervals continues.
After image acquisition, the comparison of T1 values per voxel in each scan allows identification of permeable blood vessels and tumour tissue. Both spatial and temporal resolution must be adjusted to obtain an adequate sampling of the contrast enhancement over time, for each tissue voxel. The speed with which MRI images must be acquired necessitates larger voxels, so as to maintain adequate signal-to-noise ratios. Thus, DCE-MRI is often not as high in resolution as conventional T2-weighted sequences.

Range of biomarkers
Although DCE-MRI can be performed on conventional scanners (typically 1.5 T), it requires specialist image analysis to analyse the enhanced biomarker information which is to be provided. Such information includes tissue perfusion, vascularity, endothelial permeability, cellularity etc.
The biomarkers can be used to provide measurements of tumour vascular function and to improve the diagnosis and management of diseases in a variety of organs.

DCE-MRI in the brain
Clinical applications of DCE-MRI have principally focused on in-vivo characterization of tumours.
One of its earliest applications was to analyse blood vessels in a brain tumour, since the blood-brain barrier (BBB) blocks the contrast agent in normal brain tissue, but not in vessels generated by a tumour.
The contrast agent’s concentration is measured as it passes between the blood vessels and the extracellular space of tissue, and then as it returns to the vessels. In tissues with healthy cells or high cell density, the re-entry of the contrast agent into vessels is quicker since it cannot pass cell membranes. In tissues which are damaged or have a lower cell density, the agent is present in the extracellular space for a longer duration.

Numerous DCE-MRI studies on the brain have researched the correlation between BBB disruption and diseases such as acute ischemic stroke, pneumococcal meningitis, brain metastases, multiple system atrophy, multiple sclerosis and Type-II diabetes. One of the most exciting areas of research is the difference in signal intensity profiles over time between Alzheimer’s disease patients and controls.

Tumours and DCE-MRI
Elsewhere, researchers have also established the benefits of DCE-MRI for differential diagnosis of tumours in the head and neck region, such as salivary gland tumours and lesions in the jaw bone. DCE-MRI has also been used to demonstrate the nature of a lymphoma and making a differential diagnosis versus other lesions.
Prostate cancer is becoming a major area of application for DCE-MRI. One of the key limitations to standards of care in the past was the need for random prostate biopsies after discovery of elevated PSA values. This often led to discovery of inconsequential tumours. Meanwhile, the very same biopsies sometimes missed out on significant disease. DCE-MRI, in conjunction with PSA, can identify tumours likely to cause death if left untreated.

Assessing response to chemotherapy
DCE-MRI is also being used to assess responses to chemotherapy. One example of an ongoing project in this area is CHERNAC (Characterizing Early Response to Neoadjuvant Chemotherapy with Quantitative Breast MRI), which is funded by the Breast Cancer Campaign in the UK.
Elsewhere, DCE-MRI has shown promise in detecting cancer recurrence. For example, biochemical relapse after radical prostatectomy can occur in as much as 15 to 30percent of prostate cancer patients. Detection of tumour recurrence in such cases can be difficult due to the presence of scar tissue. Determining the precise site of recurrence since patients with isolated recurrence could benefit from less-invasive treatments, such as radiation to the resection bed.
Other areas for DCE-MRI application include cardiac tissue viability – for example, to evaluate sub-clinical fibrosis and micro-vascular dysfunction. Researchers have also shown its utility in measuring renal function and partial/segmental liver function.

A full spectrum of methods
In general, the analysis of DCE-MRI is based on a full spectrum of methods from the qualitative to quantitative, with an intermediary semi-quantitative approach.

Qualitative analysis
Qualitative analysis is visual and depends on clinical experience and expertise. It assumed that tumour vessels are leaky and more readily enhance after IV contrast material is expressed. As a result, DCE-MRI patterns for malignant tumours show an early and rapid enhancement of the time-intensity curve (TIC) after injection of the agent, followed by a rapid decline. On the other hand, normal tissue shows a slower and steadily increasing signal after agent injection.

Quantitative analysis
Quantitative analysis is based on the pharmacokinetics of contrast agent exchange. It is complex, but allows for a degree of comparability. The limitation is due to a lack of standards. However, better and wider use of software has led to a growing consensus on approaches to quantitative analysis of DCE-MRI data.
One of the most widely used tools is the Toft and Kermode (TK) model, which is showing considerable promise in predicting and monitoring tumour response to therapy.

TK provides data about the influx forward volume transfer constant, KTrans, from plasma into the extravascular-extracellular space (EES). Ktrans is equal to the permeability surface area product per unit volume of tissue, and represents vascular permeability in a permeability-limited situation (high flow relative to permeability), or blood flow into tissue in a flow-limited situation (high permeability relative to flow). KTrans is known to be elevated in many cancers.

Pharmacokinetic modeling for analysing DCE-MRI dates to the early 1990s, and was followed by a consensus paper at the end of the decade ( Tofts P.S., Brix G., Buckley D.L., Evelhoch J.L., Henderson E., Knopp M.V. Contrast-enhanced T 1 -Weighted MRI of a diffusible tracer: Standardized quantities and symbols. Journal of Magnetic Resonance Imaging. 1999′).
Over the years, improvement of imaging techniques (e.g. higher temporal resolution and contrast-to-noise ratio) and greater knowledge of the underlying physiology have catalysed development of more complex pharmacokinetic models.
The TK model, for example, had been developed for measuring BBB (blood-brain barrier) permeability, and overlooked the contribution of the plasma to total tissue concentration. However, as the model gained popularity in assessing tumours throughout the body, vascular contributions to signal intensity were also included.

Semi-quantitative models
The semi-quantitative model seeks to fit a curve to data. Like the visual/qualitative, this approach also assumes early and intense enhancement and washout as a predictor of malignancy. However, semi-quantitative analysis also calculates a variety of dynamic curve parameters types after initial uptake, such as the shape of the time-intensity curve (TIC), the time of first contrast uptake, time to peak, maximum slope, peak enhancement, and wash-in and washout curve shapes.
Broadly speaking, there are three types of curve: Type 1 (persistent increase), Type 2 (plateau) and Type 3 (decline after initial upslope). One of the most attractive features of the semi-quantitative model is its relative simplicity in using parameters to differentiate malignant from pathologic but benign tissue.
For example, in the head-and-neck region, a rapid increase in TIC (fast wash-out pattern) indicates a strong possibility of Warthin’s tumour – a benign, sharply demarcated tumour. A persistent increase suggests the possibility of pleomorphic adenoma. A plateau pattern with a slow washout is characteristic of both a malignant tumour and adenoma.

In spite of enthusiasm about the semi-quantitative approach, it cannot be generalized across acquisition protocols and sequences as well as several other factors which impact on MR signal intensity. In turn, these affect curve metrics, such as maximum enhancement and washout percentage. Differences in temporal resolution and injection rates can also change the shape of wash-in/washout curves, making comparison difficult. Finally, such descriptive parameters provide no physiologic insights into the behaviour of the tumour vessels.

The limitations of DCE-MRI
DEC-MRI itself faces some major limitations. Firstly, there is a lack of standardization in DCE-MRI sequences and analysis methodology, making it difficult to compare published studies. In general, shorter acquisition times lend themselves to more comparability.
One frequent problem is movement by the patient and organ motion (e.g. in the gut, the kidney, bladder etc.). Since a DCE-MRI study procedure is over 5 minutes, there can be considerable misregistration between consecutive imaging slices, leading to noise in the wash-in and washout curves, and problems fitting pharmacokinetic models to the curve.
New DCE-MRI postprocessing software seeks to correct this by automatically repositioning sequential images for better alignment. However, these too do not use common algorithms to process the data and generate parametric maps and can show differences – e.g. in tumour vascularity. To enable further investigation of the value of DCE-MRI of the prostate, the technique of DCE-MRI and the pharmacokinetic model used to analyse it must become more standardized.

One of the most serious problems with DCE-MRI, however, is its non-specificity which can lead to to both false negatives and false positives.
Other sources of uncertainty in DCE-MRI studies include a lack of data. For example, one typical assumption is fast water exchange between compartments in spite of suspicions about the influence of restricted water exchange. Indeed, many quantitative models disregard intracellular space since it is assumed that there is no contrast media exchange. However, others have pointed out that water itself can exchange between the cell and the extracellular space, thereby influencing signal changes in the extracellular space. This is clearly an areas which calls for more study.
Further research is also required in areas such as relaxivity values for a contrast agent, field strength and tissue/pathology. Currently, relaxivity across tissues and compartments is generally assumed to be uniform.

To conclude, DCE-MRI is a significant and promising diagnostic modality. However, for most clinical applications, it cannot be used on a standalone basis, regardless of curve shape or intensity of enhancement. DCE-MRI needs to be viewed in the context of other MRI parameters such as diffusion-weighted MRI and MR spectroscopic imaging as well as T2-weighted MRI.

The clinical decision support (CDS) system is one of the most exciting areas of healthcare IT. It leverages state-of-the-art IT tools ranging from data-mining algorithms to complex neural networks, and seeks to address one of healthcare IT’s biggest challenges – Big Data. For its proponents, CDS is a means to standardize clinical practice with a framework of evidence-based clinical rules.

Information overload and CDS
In a recent publication, Ken Ong, Chief Medical Informatics Officer of New York’s Queens Hospital, discusses the importance of CDS tools and processes to modern medical practice. He cites the quadrupling in medical journal articles from 200,000 in 1970 to over 800,000 in 2010, and calculates that given the current rate of publication in medical literature, a medical school graduate reading two articles every day ‘would be 1,225 years behind at the end of the first year.’ Another interesting figure concerns national clinical care guidelines for preventive services and chronic disease management. Ong writes that were physicians to follow all these, alongside doing their routine tasks for a typical patient panel, they would need a workday of 21.7 hours. His conclusion is simple: ‘Information overload coupled with a paucity of time suggest the value of CDS and greater team-based care.’

Reduction of inappropriate imaging
In its radiology incarnation, a CDS platform provides evidence-based information and patient-tailored tools to make imaging decisions at the point of care. The system is optimized within clinical workflow and allows a physician to quickly determine what type of imaging exam is needed for a patient with specific symptoms, effectively steering choices away from low-yield exams. This ensures the appropriate use of radiation, while avoiding unnecessary exposure. It also evidently save costs.
In practical terms, radiology CDS is provided as an interface to a computerized physician order entry (CPOE) system. In February 2012, The Journal of the American College of Radiology’ published results of a pilot study at Boston’s Brigham and Women’s Hospital on a web-enabled (CPOE) system with embedded imaging decision support. The project was run between 2000 and 2010 across the hospital’s outpatient, emergency and inpatient departments and established significant increases in meaningful use for electronically created studies (from 0.4 percent to 61.9 percent) and for electronically signed studies (from 0.4 percent to 92.2 percent).
Also in 2012, the American College of Cardiology announced the results of a two-year old initiative known as Imaging in FOCUS’, which aimed at reducing inappropriate use through CDS software. The initiative had considerable success, with participating practices reporting a sharp reduction in inappropriate ordering, by close to 50% in one year (from 12 to 7 percent).

Laggard in healthcare IT
In spite of this, CDS has until recently been limited to prescriptions, laboratory tests and treatment protocols, with imaging described as ‘a laggard on the health IT technology adoption curve.’
In the US health IT investments of higher priority to hospitals-certified electronic health record (CEHRT) technology needed to comply with the federal meaningful use (MU) programme, better security systems, and ICD-10 conversion software-have superseded investments in radiology CDS.

A boost from PAMA
However, radiological CDS systems received a boost in the US after passage of the Protecting Access to Medicare Act (PAMA) in April 2014. Although much of its focus is on physician reimbursement, PAMA also provides incentives to change physician behaviour with regard to imaging. The key clause in PAMA is Section 218 which encourages the development and use of clinical practice guidelines for ordering imaging tests. These guidelines, in turn, form the core of radiology decision support tools.
PAMA closes a gap in the meaningful use clauses of the EHR Incentive Reimbursement Program, which has been targeted at the electronic health record.
EHR design does not accommodate radiology workflow and processes – and therefore had little relevance for radiologists so far. This is what PAMA seeks to address.
The impact of PAMA on CDS is likely to be major, after it takes effect. The deadline was originally set for January 1 next year, but has since been shifted to ‘approximately the summer of 2017,’ in order to give more time to healthcare providers to get used.
After PAMA is in force, physicians in their office, in the hospital outpatient or emergency department settings will have to consult appropriate use criteria (AUC) when ordering CT, MRI and nuclear medicine-based imaging such as PET (X-ray, fluoroscopy, and ultrasound exams are excluded). PAMA explicitly states that physicians offering diagnostic interpretation will be reimbursed by Medicare only for claims which confirm that a certified CDS system was used.

ACR Select: appropriate use for imaging
Although there are several initiatives, the radiological CDS system which seems most likely to become a global reference is ACR Select. This system, which debuted at the Radiological Society of North America (RSNA) Annual Meeting in 2012, was developed jointly by the American College of Radiology (ACR) and National Decision Support Company (NDSC). ACR Select is designed to ‘reduce inappropriate use of diagnostic imaging’ by using CDS software to track AUC criteria.
ACR Select offers a database with more than 130 topics and 614 variant conditions that provide evidence-based guidance for the appropriate use of all imaging procedures. More than 300 volunteer physicians, representing more than 20 radiology and non-radiology specialty organizations, participate on the ACR expert panels to continuously update these guidelines.
An ACR Select interface is provided for computerized physician order entry (CPOE) applications. The interface pops up when a physician requests an imaging exam for a patient. The physician is required to input information on the latter’s clinical condition, along with the imaging exam sought. ACR Select then gives an appropriateness score, accompanied by a colour code – green, yellow, or red which instructs whether a study is clinically indicated based on the ACR’s appropriateness criteria.

Europe sees no need to reinvent the wheel
Developments in the US have spilled over into Europe.
In autumn 2013, Hospital Clinic of Barcelona started to test ACR Select, with the aim of adapting its appropriateness criteria to European standards of practice. Shortly afterwards, a team of senior radiologists began work developing Europe-specific and evidence-based imaging referral guidelines. These were based not only on translating the US criteria into Spanish, but also adapting them to local clinical situations, diagnostic codes, and country-specific practices. The target was ‘to cover around 80 percent of requests in daily practice by reviewing the clinical scenarios, indications and recommendations’ for a large range of topic groups.
The embryonic system was subsequently tested at 80 general practitioners in Hospital Clinic Barcelona’s network. The GPs were provided feedback on how their requests for imaging exams matched appropriateness criteria. The tests were then rolled out to other specialists, including emergency physicians.

At the European Congress of Radiology (ECR) in Vienna in March 2014, Dr. Lluis Donoso Bach, director of the diagnostic imaging centre at Hospital Clinic of Barcelona, pointed out that the economic crisis had led radiologists looking for innovative ways ‘to do more with less.’ Europe, he said, could benefit by adapting ACR Select to its needs, and avoid going through an exhaustive process of creating its own criteria for appropriate imaging.
In the months to come, some ten pilot projects to adapt ACR Select to Europe were launched in various other European countries, including the United Kingdom, Germany, Italy, Spain, Portugal, and Sweden.

Conflicts in European models, global ambitions
In retrospect, one of the most persuasive arguments swinging the choice of radiology CDS towards ACR Select consisted of conflicts between emerging European CDS models. The ESR had first sought to develop a CDS system based on guidelines from the French and British radiological societies. However, preliminary work soon identified considerable discrepancies’ between the two sets of rules and this led the ESR to turn to ACR Select.
Yet another advantage of a joint Euro-American approach is acknowledged by the ESR. It gives ‘a global dimension for the ACR and ESR’s common vision of establishing a global set of imaging referral guidelines in the future.’ As Pharma Times’ noted, the collaboration is ‘a decisive first step towards harmonizing AUC for imaging at a global level’. It added that interest in the system from Australia and Asia suggests ‘that the radiology field is indeed headed towards a globalization of ordering guidelines.’
In March 2016, National Decision Support Company (NDSC) established a European subsidiary in Vienna, home of the ESR. Outside Europe, one of its first targets is the Middle East.

ESR launches Europeanised prototype
In March 2015, the European Society of Radiology (ESR) formally launched a prototype of the adapted US CDS system, which it called iGuide. The launch took place at the ECR in Vienna. During the occasion, Dr. Lluis Donoso Bach also took over as ESR President, with his term lasting until 2016.
During the launch, Erika Denton, National Clinical Director for Diagnostics with NHS England, discussed some figures regarding the localization and adapting of ACRSelect into the ESR iGuide. There were 16% rating changes – that is, changes in the ratings attributed to an orderable imaging exam; 9 % category changes – that is, changes in the imaging modality being recommended in a given clinical scenario.

iGuide
iGuide makes evidence-based, imaging referral guidelines available and easy to use across Europe. It is designed as a user-friendly system available at the point of care, and can be stand-alone or integrated with ordering systems and linked to electronic health records. As with ACR Select, it aims to ensure ‘a simpler, faster and reliable clinical workflow.’
iGuide also retains an element of flexibility. Users can localize recommendations according to their needs starting from the evidence-based core. In addition, the ESR iGuide can be adapted to users’ needs and institutional settings, for example by taking into account the availability of certain types of imaging equipment. This is not only relevant for Europe, but across other heterogeneous global markets, and will be crucial to eventually make the Euro-American effort an international success.
The ESR plans to continuously update iGuide to provide users with the latest evidence, instead of publishing a complete overhaul every few years.

Cardiovascular disease (CVD) is by far the leading cause of death in industrial countries. However, there are significant differences by continent/region, and even more so in terms of gender. There have also been some major recent changes in the evolution of CVD, compared to another major source of mortality – cancer. Once again here, there are some female-specific factors of interest.

The US and Europe
For Europe as a whole, latest figures from the World Health Organization (WHO) show CVD accounting for 45percent of deaths, approximately the same level as the US, where the figure is 44percent.
Cancer is the second largest cause of death in both the US and Europe. However, a significant margin separates its mortality impact from CVD.
There are also differences between the US and Europe in the relative impact of CVD versus cancer. In the former, cancer accounts for 32percent of deaths (or almost three-fourths of that from CVD). In Europe, the share of cancer is less than half CVD deaths. The WHO data cover 52 countries in Europe, including all members of the European Union (EU).

A man’s illness ?
Traditionally, heart disease was thought of as a man’s’ illness, although approximately the same number of women and men died each year of heart disease in the US and the EU.
Indeed, gender issues in CVD deaths are significant, both in the US and Europe. Although a higher number of males die in the US from CVD as compared to females, the share of CVD as a cause of death is only slightly higher in American women (44.3percent vs. 43.4percent).
In Europe, the gap is far more dramatic, with CVD accounting for 51percent of deaths among women and 42percent among men.

Cancer replaces CVD as leading cause of death in northern/western Europe
There are nevertheless considerable divergences across European countries in CVD mortality as well as in recent changes in death rates due to CVD.
In ten advanced EU countries, more men now die from cancer than CVD. These countries are Belgium, Denmark, France, Italy, Luxembourg, the Netherlands, Portugal, Slovenia, Spain, and the UK. The case is the same for an EU non-member, Norway. Conversely, the highest numbers of deaths from CVD tend to be seen in Eastern European countries.
In much of Europe, however, latest WHO data show more than double the number of deaths from CVD compared with cancer, in women. 15 countries in this group report CVD causing more than four times the number of deaths in women as cancer, compared to only 6 for men.
Meanwhile, death rates from CVD have declined in all countries over the past ten years. However, in some countries, women have seen a relatively lower fall than men in age standardized mortality rates, over the period. These include Luxembourg (50percent for men vs. 42percent for women), the Netherlands (39percent vs. 32percent) and Sweden (31percent vs. 26percent), and to some extent Ireland, Italy and Switzerland.

Raising awareness
One immediate priority for health professionals and policy makers is to raise awareness about CVD and women. Currently, Red Day’, Go Red for Women’ and Women at Heart’ campaigns by professional societies and patient groups in the US and Europe have sought to boost awareness further, and do this faster.
The reasons for this are evident. In the US, just over half of women surveyed recognize heart disease as their Number 1 killer, according to a 12-year follow-up study published in 2010 in Circulation: Cardiovascular Quality Outcomes’.
Nevertheless, the situation had improved significantly compared to the baseline year of 1997 when only 30 percent identified heart disease as the leading killer of women, with 35 percent believing that cancer took this role.
The situation is worse in parts of Europe. In Ireland, for example, a recent Irish Heart Foundation report showed that less than one in 5 Irish women knew CVD as being the leading cause of female mortality.

CVD protection in younger women
The reasons for believing CVD was a man’s’ disease (as mentioned above) were not simply hearsay. Women are protected by their hormones against CVD during their child-bearing years. However, this protection is lost as soon as they enter menopause. The net result is that women tend to get CVD at an age about 10 years more than men.
To complicate matters, CVD symptoms in women are sometimes different from those in men. This adds to under-recognition of heart disease in women. For example, heart attack symptoms in women such as chest pain can be less profound than in men. Women may only feel an uncomfortable pressure in the chest centre which occurs sporadically or lasts a few minutes, or experience pain in one or both arms, their neck, back or stomach, along with shortness of breath and accompanied by a cold sweat, nausea, vertigo and weakness. Moreover, it has also been established that women have a higher prevalence of silent ischemia and of unrecognized myocardial infarction than men.
As a result, both women and physicians need to be trained to recognize female-specific symptoms.

HRT and CVD risks
One of the beliefs which has endured for several decades is that the estrogen drop during menopausal transition induces increased post-menopausal CVD risk in women, probably through harmful changes in CVD risk factors. One of the findings supporting this conclusion was that women who reached menopause before the age of 40 had a two-year lower life expectancy than women with a normal or late menopause.
Indeed, circulating estrogens do have a regulating effect on several metabolic factors, such as lipids, inflammatory markers, and the coagulation system.
This was the reason for the popularity of Hormone Replacement Therapy (HRT), or exogenous estrogens. Until recently, HRT was recommended for use in post-menopausal women to limit CVD risk. The hypothesis was supported by several observational studies, but could not be conclusively proved in large randomized trials. Instead, HRT was shown to increase CVD event rate in older (>60 years) post-menopausal women. As a result, clinicians now recommend a careful evaluation of the risk/benefit of HRT replacement for preventing CVD, and the use of HRT has declined.

Concurrent risk factors for women
Other, concurrent risk factors include hypertension, hypercholesterolemia, hypertriglyceridemia and metabolic syndrome. These increase in women over the age of 45, or a few years before menopause.
For example, systolic blood pressure rises steeply in older women compared with men. Hypertension is associated strongly with a higher prevalence of left ventricular hypertrophy and diastolic heart failure (HF). Studies have shown that even borderline hypertension (less than 14/9 cm Hg) causes more cardiovascular complications in females than in men.
At younger age, the prevalence of hypercholesterolemia is lower in women than men, but at over 65 years age, mean LDL-cholesterol levels are higher in women. Hypertriglyceridemia and low HDL-C levels are far more important risk factors for CVD in women than for men, as discussed below.

Type 2 Diabetes
Nevertheless, of the biggest areas of concern is Type 2 diabetes mellitus, which poses a much higher greater risk for cardiovascular complications in women than in men.
One meta-analysis of 37 prospective cohort studies published in the British Medical Journal’ in December 2006 found mortality risk to be 50percent higher in women with diabetes compared with men. In addition, it has been shown that Type 2 diabetes is a potent, independent risk factor for heart failure in women. However, this cannot be fully explained by coexisting cardiovascular risk factors or previous myocardial infarctions.

Lifestyle factors
Lifestyle changes also play a role. Obesity, for example, is a major CVD risk factor. It is more prevalent in men under the age of 45, but has begun to increase with advancing age in women, reducing the gap with time, and often reversing it in older women. This was one of the findings of a report called European Heart Health Strategy: Red Alert on Women’s Hearts’, published in 2009 by the EuroHeart Project, funded by the EU Commission and conducted jointly by the European Heart Network (EHN) and the European Society of Cardiology (ESC).

Women and clinical trials
The case of HRT, where findings from large randomized trials reversed those of observational studies, has brought another priority to the forefront, namely to increase the presence of women in CVD clinical trials.
The EU-funded EuroHeart project (see above) found women to be under-represented in many trials, even where important gender differences are present within most areas of heart disease. The proportion of women enrolled was 27-41percent, even though the female prevalence of clinical conditions under study in the general population was similar for both men and women.
The case in the US is similar, in spite of a legal requirement that research funded by tax receipts must include women and minority groups. One study found that trials by the National Heart Lung and Blood Institute, attached to the National Institutes of Health (NIH), enrolled 38percent women for the years 1965-1998. This fell further to 27percent in 1997-2006. Furthermore, only 13 of 19 studies analysed gender differences.

Apart from the traditional belief that CVD was a man’s’ disease, some experts believe that cost may also have been a consideration in under-recruitment of women, whose hormonal fluctuations tend to complicate pharmacokinetic and pharmacodynamic analysis.
Nevertheless, given the growing burden of CVD in middle-aged women relative to men, it is evident that greater gender-specific cardiovascular research is required to adapt existing guidelines for better cardiovascular health in women.

Pregnancy as stress test for future CVD
There is intriguing evidence that pregnancy might be a useful stress-test’ for future CVD risk. Hypertensive disorders in pregnancy have been shown to be predictors for CVD events in later life. Impaired glucose tolerance and gestational diabetes in pregnancy are also female-specific risk factors for the development of diabetes and metabolic syndrome in young women.
One of the conditions under close scrutiny is pre-eclampsia, which is characterized by high blood pressure and large amounts of protein in the urine. Although the etiology of pre-eclampsia has yet to be established with certainty, the hyperlipidemia of normal pregnancy (elevated total cholesterol and triglycerides) becomes more extreme in women developing the condition. The sharp growth in triglycerides leads to increased production of LDL (up to 3-4 times more than in a normal’ pregnancy), along with reduced HDL-C. Together, this contributes to endothelial dysfunction.
One ongoing trial at Brigham and Women’s Hospital in Massachusetts seeks to demonstrate an association between pre-eclampsia during pregnancy and altered blood vessel function and abnormal hormone levels in later life. The trial, known as Preeclampsia: A Marker for Future Cardiovascular Risk in Women’ commenced in 2012. Its results are expected to be published in the near future.