Ionizing radiation, from the sun and even the earth, is a daily fact of life. There is little that can be done about this, except to stay away from too much sunlight and protect the skin with sunscreens. On the other hand, people are also sometimes exposed to radiation for medical reasons – such as diagnostic X-Rays or CT scans, or a range of interventional radiology procedures. These procedures offer tremendous benefits for patients and for healthcare providers. The evidence for such benefits has become indisputable in recent years, and covers a wide range of diseases and conditions.

Medical imaging has profound impact on patient management
The American Journal of Roentgenology’ reported in 2011 that abdominal surgeries reduced significantly after CT scans. Physicians planned to admit 75percent of patients to hospital before CT. This level was changed to hospital discharge with follow-up in 24percent of patients after CT. The conclusions of the researchers, from Massachusetts General Hospital, were conclusive: CT ‘changes the leading diagnosis, increases diagnostic certainty, and changes potential patient management decisions.’
Massachusetts General Hospital was indeed one of the first institutions to study the impact of medical imaging. In 1998, a team from the hospital reported that CT was 93-98percent accurate in confirming or ruling out appendicitis. The condition accounted for 1 million patient-days per year in the US, with a similar level eventually found to have other conditions.

From emergency rooms to lung cancer
More recently, the New England Journal of Medicine’ published a study on non-invasive coronary CT imaging in the emergency room. The study found that out of the 8 million visits per year to emergency rooms by patients with chest pain, only 5-15percent were eventually found to be suffering from heart attacks or other serious cardiac diseases. As many as 60percent of patients faced unnecessary admission and testing to exclude acute coronary syndrome.
Meanwhile, it has also been reported that low-dose CT screening reduced lung cancer deaths by at least 20percent in a high risk population of current and former smokers aged 55 to 74. These findings were reported by the National Lung Cancer Trial in the US.

Fight against Alzheimer’s, speeding up clinical trials
In the future, medical imaging holds forth significant promise as a tool in the fight against diseases ranging from osteoporosis to Alzheimer’s, whose incidence is likely to grow sharply as the population ages.
Medical imaging also offers increasing promise as a surrogate endpoint in clinical trials, allowing measurement of the effect of a new drug far earlier than traditional endpoints, such as survival times or clinical benefit.

Concerns about over-use, some alarmist
Nevertheless, there are several concerns about over-use’ – especially for imaging accompanied by radiation such as CT. In the US, according to a June 2012 review in the Journal of the American Medical Association’, CT scans tripled in the period 1996-2010, corresponding to a 7.8percent annual increase. Although this was less than a near four-fold increase in MRI and a 30percent fall in nuclear medicine use, CT has been the target of sometimes emotive campaigns.
One good illustration of this was an Op-Ed in the New York Times’ on January 31, 2014. The article was titled ‘We Are Giving Ourselves Cancer.’ It opened with the observation that we are ‘silently irradiating ourselves to death,’ while its closing sentence urged finding ways to use CTs ‘without killing people in the process.’

The Times’ Op-Ed cited a British study which ‘directly demonstrated’ evidence of the ‘harms’ of CT, and it is here that its authors over-stretched their credibility. The study they referred to was published in Lancet’ in August 2012 and titled Radiation exposure from CT scans in childhood and subsequent risk of leukemia and brain tumours: a retrospective cohort study’. Its authors used data on 175,000 children and young adults and found that the cumulative 10-year risk was higher in relative terms, but translated into one extra case of leukemia and one extra case of brain tumour per 10,000 head CT scans.

ALARA and the principle of necessity and justification
In other words, while few would argue that there is no risk from radiation, it is clear that such risks are small and that even these small potential risks could be controlled further by reducing exposure to radiation.
Both industry and healthcare professionals are endeavouring to ensure that such a goal is achieved.
Manufacturers of CT and other radiation imaging equipment seek to keep exposure to radiation for both patients and medical staff to a minimum – and below their regulatory limits – by using the ALARA (As Low As Reasonably Achievable) principle to design their products. Key methods include use of the most dose-efficient technologies available and seeking to ensure that optimum scan parameters are used for a patient and examination type.
Meanwhile, in the clinical setting, doctors seek to ensure that radiation imaging examination is ordered only when absolutely necessary and justified, while radiographers optimize the radiation dose used during each procedure.

Safety, information and awareness
Since the mid-2000s, radiologists and medical physicists have taken steps to increase controls on radiation risks to patients. These have essentially focused on promoting the safe use of medical imaging devices, supporting informed clinical decision making and increasing patient awareness.
One of these initiatives is known as Image Gently, a collaborative initiative by radiology professional organizations and other concerned groups. Its target is to specifically lower radiation dose during the imaging of children.
A related initiative, led by the American College of Radiology (ACR) and the Radiology Society of North America (RSNA), is Image Wisely. This is essentially an awareness campaign whose goals are to eliminate unnecessary’ procedures and lower doses to minimal levels required for clinical effectiveness when necessary. One aspect of Image Wisely is collaboration between medical radiologists and manufacturers to improve performance of radiology equipment and allow physicians to make real-time assessments of whether radiation levels are acceptable.

Initiatives by professional societies
Such initiatives are closely supported by professional radiology societies. The ACR has developed Appropriateness Criteria (corresponding to the federal requirements on appropriate use) to assist referring physicians and radiologists in prescribing the best imaging examination for patients – based on symptoms and circumstances. One tool consists of the display of imaging options and associated radiation levels for a specific procedure. The aim is to reduce imaging examinations by assuring that the most suitable exam is done first.
In Europe, the European Society of Radiology’s flagship EuroSafe Imaging’ has the same objective, to maximize radiation protection and quality/safety in medical imaging. The initiative was launched at the European Congress of Radiology in 2014 and has so far attracted over 50,000 individual supporters (known as Friends of EuroSafe Imaging’). Over 200 institutions (industry and healthcare providers) have also endorsed the initiative.

Accreditation programmes
Accreditation programmes are also being targeted by the ACR and ECR, in order to assess facilities based on imaging competence, adherence to latest dose guidelines, and personnel training. Given the pace of technology development in imaging, certified radiology and nuclear medicine professionals are increasingly recommended or (in some cases) required to earn continuing education credits on radiation safety.
In Europe, the ECR has joined forces with the European Federation of Organizations for Medical Physics (EFOMP), the European Federation of Radiographer Societies (EFRS), the European Society for Therapeutic Radiology and Oncology (ESTRO), the European Association of Nuclear Medicine (EANM), as well as the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) on an EU-promoted radiation education project called MEDRAPET. The findings, published in 2014, revise the previous Radiation Protection 116 Guidelines on Education and Training.

The Bonn Call for Action sets roadmap for the future
Many of these initiatives have been inspired by a conference held in Bonn, Germany, at the end of 2012, which was sponsored jointly by two United Nations bodies – the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). The outcome of the conference, which was attended by participants from 77 countries, is known as the Bonn Call for Action, and aims to strengthen medical radiation practices into the 2020s.

The Bonn Call consists of ten major actions. These are described below:

• To enhance implementation of the principle of justification. There is explicit emphasis on the use of clinical decision support (CDS) technology towards such a goal.
• To enhance implementation of the principle of optimization of protection and safety. There is a specific call to ensure the establishment, use and regular updating of diagnostic reference levels for radiological procedures, including interventional procedures, and to develop and apply technological solutions for patient exposure records, harmonize dose data formats provided by imaging equipment and increase utilization of electronic health records.
• Strengthen manufacturers’ role in contributing to the overall safety regime. This seeks to enhance radiation protection features in the design of both physical equipment and software, and to make these available as default features rather than optional extras.
• Strengthen radiation protection education and training of health professionals.
• Increase availability of improved global information on medical exposures and occupational exposures in medicine, with specific attention to developing countries.
• Improve prevention of medical radiation incidents and accidents. One interesting facet here is a call to work towards including all modalities of medical ionizing radiation as part of a voluntary safety reporting process, with specific emphasis on brachytherapy, interventional radiology, and therapeutic nuclear medicine, in addition to external beam radiotherapy.
• Strengthen radiation safety culture in healthcare.
• Foster an improved radiation benefit-risk-dialogue.
• Strengthen the implementation of safety requirements globally.
• Develop practical guidance to provide for the implementation of the International Basic Safety Standards in healthcare globally.

Although some of the Bonn Call points are repetitive, the document is noteworthy in terms of setting a minimal set of common rules for a very wide range of stakeholders – manufacturers, health professionals and professional societies.

Point 6 seeks new work on effective’ dose
Point 6 of the Bonn Call is both ambitious and timely. Although the concept of effective dose’ (or effective dose equivalent) was introduced in the mid-1970s to provide a common framework for evaluating the impact of exposure to ionizing radiation via any means, technology’s uneven leaps have not made it easy to follow through. Data for doses by different radiographic imaging modalities used in radiation therapy are scattered widely through literature, making it difficult to estimate the total dose that a patient receives during a particular treatment scenario. In addition, interventional systems are often configured differently from diagnostic set-ups and imaging systems do not distribute radiation in similar ways. For example, planar kV imaging attenuates rapidly along the line of sight, while CT dose is uniformly distributed through a patient. This makes it difficult to sum dose in a radiobiologically consistent manner.

Mobile health or mHealth has recently become one of the fastest growing and potentially disruptive segments of healthcare technology. Some typical mHealth segments include medication reminders, remote patient monitoring and wellness management. Key challenges faced by mHealth include data storage and management, network availability and maintenance, compatibility and interoperability. The single biggest issue however is considered to be security and privacy – in terms of access control, infrastructure integrity and data anonymity.

M&A, drug costs and mHealth shake up US healthcare
In December 2015, consultants PricewaterhouseCoopers (PwC) said that mHealth ranked just behind mergers & acquisitions (M&A) and the escalating costs of prescription drugs as a key factor shaking up US healthcare.
PwC noted that one reason for such an impact was mHealth’s status as a late starter. Smartphones and apps have been relatively underutilized by the healthcare industry, and playing catch-up has catalysed an ultra-fast pace of growth. The consulting firm noted that 71% of US adults now own a web-enabled smartphone or wireless device and users with health or fitness apps doubled from 16% to 32% in 2015 compared to the year before.
Other figures endorse the enthusiasm about mHealth.
93% of US clinicians now believe that mHealth apps can improve patient’s health, according to a GreatCall survey on their rising popularity. This is well above a level of just 52% in 2013, according to a survey cited by US telecoms carrier Qualcomm. That report also noted that another 16% percent also noted ‘that the use of mobile technology will dramatically change the way that healthcare is delivered in the future.’

Europe and mHealth
The picture is more nuanced in other parts of the world.
In Europe, for example, Pew Research figures show smartphone penetration is roughly equal to US levels in northern countries such as Sweden, Denmark and the Netherlands, as well as on the other side, in Spain. The levels are 60-70% in Germany and the UK and 50% in France. These three, together, account for 45% share of the European mHealth market.
There also are some major differences between European countries in the mHealth climate, as another recent report, by Germany’s r2G, shows. As a result, usage of ePrescription varies dramatically, from 0 all the way to 100%. In Europe, regulatory differences can indeed have profound implications for mHealth. For example, ‘remote treatment of patients is prohibited’ in Germany, ‘whereas in Spain telemedicine is encouraged.’
In spite of being Europe’s largest economy, Germany remains a major challenge. According to a report from FTI Consulting, ‘only 28% of German hospitals have a clear strategy’ on digital healthcare. In spite of this, a proposed new law on eHealth ‘does not even mention the opportunities’ provided by mHealth (or personalized medicine). In effect, Europe has some way to go before it approaches mHealth benchmarks in the US, where doctors in several states can ‘bill health insurance companies for the costs of email-based consultations,’ according to a survey by A.T Kearney.

India among most mHealth-ready
Overall, revenues in the global mHealth market are expected to rise annually at a rate of 33.5% between 2015 and 2020, based on forecasts in an Allied Market Research report. Leading the pack will be the Asia-Pacific, with a growth rate estimated by Allied at more than 35%.

India is a special case for several reasons. Although Pew reports penetration of just 17% in the country in 2015, India recently overtook the US to become the second largest market for smartphones, after China (where penetration is much higher, at 58%).
Indeed, the speed of growth in the Indian market has surprised experts. As recently as August 2015, researchers IDC were forecasting that India would surpass the US in smartphone sales, in 2017.
India is in fact considered as one of the most mHealth-ready markets, in spite of a per capita income which is still among the world’s lowest. A survey in 2012 by PwC and the Economist Intelligence Unit (EIU) explained the reasons for the paradox: ‘In developed markets, mHealth is perceived as disrupting the status quo, whereas in emerging countries it is seen as creating a new market, full of opportunities and growth potential…. Consumers are more likely to use mobile devices and mHealth applications, and more payers are willing to cover the cost of mHealth services.’ The report notes that the pace of adoption of mHealth ‘will likely be led by emerging markets that rank highest among ten countries on a score of mHealth maturity.’

Demand driven by both business and consumers
The Indian case in the PwC/EIU survey illustrates one of the salient features for mHealth, everywhere. mHealth technology is both B2B (business-to-business) as well as B2C (business-to-consumer). Indeed, it is consumers who are pulling mHealth, in both developing and industrialized countries. This is probably less for cost than for reasons of access ( anywhere, anytime’ diagnosis, monitoring and treatment). The title of the PwC/EIU report underscores such an observation: ‘Consumers, it says, ‘are ready to adopt mobile health faster than the health industry is prepared to adapt.’

4 million downloads a day
Overall, the near-frenzied enthusiasm for mHealth is illustrated by figures from German consultant R2G. Even in 2014, it says there were over four million downloads of mHealth apps every day.
The number is expected to keep growing. By 2017, it’s predicted that 50% of smartphone users will have downloaded mobile health apps.

Hospitals and mHealth
In spite of the incipient mHealth consumer boom, heavy-hitters in industry are also marshalling their mHealth strategies.
Hospitals and health plans see mHealth as a tool to contain costs and enhance efficiency, and enhance healthcare safety and quality too. A growing number of top hospitals have begun to incorporate mHealth – the use of mobile technology devices and smartphones for healthcare purposes – to connect patients and clinicians, improve care coordination and reduce avoidable, costly hospital readmissions.

In the US, one driving force for mHealth consists of reforms imposing penalties on hospitals for avoidable readmissions. Although hospital readmissions fell from 19% in 2011 to 17.5% in 2013, more can clearly be done. According to Kaiser Health News’, 2,225 hospitals paid 227 million dollars in penalties during 2013 for high hospital readmission rates.
The reforms have provided strong incentives to implement mHealth systems – for example, to track cardiac rhythms, glucose levels and vital signs, and to identify health issues in time so as to prevent repeat trips.
Evidence for this kind of direct benefit from mHealth is provided by the prestigious Mayo Clinic, who report that use of a smartphone app during cardiac rehabilitation can reduce hospital readmissions by a factor of three. Mayo researchers found that only 20 percent of cardiac patients who used the app visited the emergency department or were readmitted to the hospital within 90 days, compared with 60 percent of those who did not use it.

The role of mHealth in increasing efficiency is apparent from Canada’s Ottawa Hospital. The Hospital and IBM have launched a mobile-enabled platform to streamline workflow and create a circle of care’ around patients. Care providers have 24/7 access to patient information, collaboration tools and available hospital resources via a custom mobile app, which has enhanced process efficiency, leading to more accurate discharge scheduling and reducing over-occupancy rates from levels of 110 percent.

European hospitals are also enthused about mHealth. In Britain, the National Health Service is encouraging remote medical monitoring and mobile health access as part of the country’s digital healthcare revolution, according to a report in The Telegraph’. The programme, which focuses on greater efficiency in providing medical services, includes use of wearables, video link consultations, e-prescription and connected clothing. Its objective is to make virtual healthcare ubiquitous within five years and save the NHS up to 5 billion pounds over a decade.

The pharmaceutical industry and mHealth
The pharmaceutical industry, too, has got into mHealth, with hundreds of mobile apps providing information on drugs, drug interactions and enabling patients to track usage. A study by Avella Specialty Pharmacy found apps focusing on HIV medication significantly boosted adherence. Despite this, it has ‘lagged in mHealth app development and adoption,’ due to concerns about liability and the need to follow strict regulatory compliance.
There are three other reasons for the lack of success. Pharma company app portfolios are not globally available. It is also built around their core products, rather than market demand. In addition, there is no cross-referencing, or a common and recognizable design providing a corporate identity.

Profiling mHealth apps
At present, some sources estimate that there are over 100,000 mobile health apps that have been developed. 85% of the apps are for wellness, while the remaining 15% (or 15,000) are directed at medical purposes. Even though a late starter, as many as 42% of mHealth apps available in major stores have a paid business model.

Nevertheless, the bulk of mHealth apps are forced to struggle.
A November 2015 survey of the global market by R2G found that 62% of app vendors attained less than 5,000 downloads per year for their entire mHealth app portfolio. 11% percent reached over 100,000 downloads. Just 2% had 1 million-plus downloads. Of the latter, about half had been in the business before 2010.
R2G said that as many as 60% of developers of mHealth apps were dissatisfied with the market reception for their apps. Many also found that the performance of the apps fell short of their goals.
The survey also reported that over half mHealth app developers were technology companies, and they viewed the presence of medical professionals on their team as a priority. In terms of targeted customers, patients with chronic conditions were most common, accounting for 48% of apps. Hospitals are the second biggest target, with 32% of developers focusing on them.
Another finding of interest was the fact that the most successful vendors were more likely to develop apps for hospitals as opposed to patients. This may be one of the strongest indicators that the mHealth apps industry still has to mature, and that there is much more to come. During the same month as the R2G survey, New York University School of Medicine released another mHealth report. The study found that though consumers frequently downloaded mHealth apps they ‘don’t necessarily use them a lot.’
For consumers at least, there is much more to explore in mHealth.

Rupture of the coronary plaque surface, accompanied by the exposure of thrombogenic, red cell-rich necrotic core material, is one of the most important underlying mechanisms in acute coronary syndrome (ACS). After decades of idling, such plaques sometimes suddenly burst into this life-threatening condition. The rupturing occurs during the evolution of coronary atherosclerotic lesions, and is often accompanied by super-imposed thrombosis.
To date, the precise mechanisms involved in plaque erosion remain generally unknown. Coronary spasm is simply a universal suspect.
Prevention is therefore considered to be the only effective means for reducing the mortality and morbidity of coronary heart disease.
Coronary lesions that are prone to rupture have a distinct morphology compared with stable plaques, and provide a unique opportunity for non-invasive imaging to identify vulnerable plaques, before they lead to clinical events.

Plethora of terminology
The severity and prognosis of plaque rupture is characterized by a plethora of terminology. Plaque vulnerability describes the risk of symptomatic thrombosis in the short term, whereas plaque ‘activity’ remains ambiguous (referring to one of a wide variety of processes associated with progression).
‘Plaque burden’ is accepted to denote extent of disease. It is a measure of the extent of atherosclerosis, regardless of the cellular composition or activity of plaques. There are various ways to measure the burden: plaque volume, lesion-coverage of arterial surface – sometimes based on using computed tomography (CT) to measure coronary calcium score, or ultrasound to assess plaque area in the carotid bed. Given that atherosclerosis is multi-focal (and impacts upon the entire vasculature), a high plaque burden in one region (e.g. the lower limbs) may be a marker for advanced disease elsewhere. The highest concern on the latter consists of the coronary arteries due to their high degree of susceptibility.

Size is not everything
Rather than plaque size alone, the risk of rupture depends more on the composition and type of plaque, inter alia, richness in soft extracellular lipids – and macrophages. Indeed, structurally what is required for plaque rupture is an extremely thin fibrous cap. As a result, ruptures are usually minuscule and occur mainly at the periphery of the cap covering the lipid-rich core – among lesions clinically defined as thin-cap fibroatheromas. They have reduced tensile strength and are more extensible than intact caps, while the presence of collagen and smooth muscle cells is lower. In effect, as extracellular lipid accumulation progresses (usually due to external stress/triggers), the fibrous cap weakens and predisposition of a plaque to rupture increases.
Several other factors are also believed to play a concurrent role, among them inflammatory cell recruitment, macrophage formation, necrosis, matrix synthesis, calcification, arterial remodelling, etc.
The interaction between these factors is not only complex but variable too, as far as the development of plaque is concerned. This leads to unpredictable rates of progression and variable clinical outcomes.

Not all ruptures lead to ACS
Nevertheless, there are, once again, certain other issues in play with regard to the clinical relevance of vulnerable plaque detection. Most plaques remain subclinical and asymptomatic. Others elicit acute thrombosis and may lead to an acute coronary syndrome (ACS).
However, not all plaque ruptures cause ACS. Some develop obstructively (stable angina). Indeed, on its own, stable angina pectoris derived from atherosclerosis is rarely fatal without scarring of the myocardium – the latter can provoke an arrhythmia presenting as sudden cardiac death.
Confusion arises in other contexts too. For example, the presence of thrombosis is not the same as the occurrence of ACS. Indeed, some physicians believe that the majority of ruptures and erosions are asymptomatic in the short term, although they may sometimes lead to gradual coronary narrowing.

Nightmare for prognosis
This lack of clarity has proven to be a nightmare. ACS occurs only when vulnerable plaque, platelet activation and impaired fibrinolysis occur alongside inflammatory states. Such vulnerability may change with time, and it is these changing dynamics vis-a-vis stress/triggers which determines the exact moment and point of rupture.  As a result, the non-invasive detection of vulnerable plaques is considered to be of great clinical relevance, especially in ultra-high risk patients.

At the cutting-edge
Currently, a host of new, non-invasive techniques are being harnessed to assess and predict the likelihood of coronary plaque rupture. Leading the way are computational fluid dynamics (CFD) and fractional flow reserve (FFR) methodologies. They are based on harnessing supercomputing capability to the analysis of CT angiography.
The high quality imaging and sub-millimetre resolution of modern computed tomography (CT) scanners allows characterization and quantification of lesions at accuracies unimaginable barely a decade ago. CFD supplements the functional information of CT-based plaque assessment by calculating lesion-specific endothelial shear stress and FFR. Such supplementation of functional information by quantified morphologic data about coronary plaques is considered to be one of the best means to detect vulnerable plaques.

FFR guided therapy
For patients with coronary calcification and hemodynamically significant obstructive disease, FFR has long been considered the best solution for guiding re-vascularization of lesions and improving outcomes. FFR provides an index of atherosclerosis and lesion significance, as measured with a pressure-sensitive angioplasty guidewire. FFR-guided therapy has improved patient outcomes, reduced stent insertions. However, it is used in less than one-tenth of cases due to procedural and operator related factors – above all, patient discomfort due to time and motion artifact as well as cost.

Coupling FFR to CT angiography
More recently, due to the developments in non-invasive CT imaging and the application of CFD modelling to CT angiography datasets, FFR can be derived non-invasively without requiring modification of standard CT angiography acquisition protocols or inducing hyperemia.
Such non-invasive FFR, moreover, has been shown to demonstrate excellent correlation with invasive FFR.

PLATFORM Study
One of the key studies investigating the impact of combining FFR and CT was called PLATFORM (the Prospective LongitudinAl trial of FFRCT: Outcome and Resource Impacts).
PLATFORM, which ran from the end of 2013 to 2015 at centres in the US and Europe, demonstrated improved patient selection for invasive angiography using a combination of coronary CT angiography (CCTA) along with fractional flow reserve CT (FFRCT). The so-called CCTA-FFRCT approach increased the chance of identifying obstructive coronary artery disease among those intended for invasive testing and held forth the promise of serving as an efficacious gatekeeper to invasive coronary angiography (ICA). 
The findings were conclusive, with numbers presented by researchers at the European Society of Cardiology at London in 2015. The use of FFRCT in patients with planned invasive catheterization, they noted, was associated with a reduction in the rate of finding no obstructive CAD at ICA, from 73% to 12%. It also resulted in cancellation of 61% of ICAs.

Computational fluid dynamics
In effect, the adoption and translation of CFD modelling may be considered to have revolutionized cardiovascular medicine.
CFD is a specialist IT discipline bringing together advanced mathematics and fluid mechanics. Its roots lie in mission-critical/high-performance engineering systems. Much of its history is intimately connected to the aerospace industry, to enhance the accuracy of complex simulation scenarios such as transonic or turbulent air flows.
In medicine, the first-ever CFD investigations began in cardiovascular research, to clarify the characteristics of aortic flow in a degree of detail below the threshold of experimental measurements. Computer-aided design (CAD) models of the human vascular system were built using modern imaging techniques, coupled to rapid, economical, low-risk 3-D prototyping. The ensuing models precisely computed factors such as blood flow and tissue behaviour and response, taking close consideration of boundary conditions such as complex systemic/physiological pressure and ‘virtualized’ metrics such as wall shear stress.

CFD modelling has already revolutionized the development of devices such as stents, valve prostheses, and ventricular assist devices.
CFD is currently being translated into cardiovascular clinical tools for minimally-invasive application to a wide spectrum of coronary, valvular, myocardial and peripheral vascular diseases. One of the biggest advantages offered by combining high-resolution imaging with CFD is that unique patient-specific data can be juxtaposed into multi-scale, variable duration models to make individualized risk prediction and planning possible. This is directly opposed to registry-based, population-averaged data.
In the future, it is expected that the trend to ‘digital patient’ representation, combined with population-scale numerical models, will reduce cost, time and risk associated with clinical trials.

The massive processing power brought to play by CFD quickly led to the understanding that mechanistic forces of arterial wall shear stress (WSS) and axial plaque force acting on coronary plaques might be responsible for both the development of coronary plaque and its vulnerability to rupture.
For example, it is difficult to measure WSS, a key factor in the development of atherosclerosis and in-stent restenosis, without invasive procedures – with all the latters’ attendant risks and frequent futility. One study demonstrated that less than a third of patients with suspected obstructive coronary artery disease (CAD) showed its presence after invasive coronary angiography (ICA), while an even-smaller number had flow-limiting obstructive disease based on invasive fractional flow reserve (FFR).
In contrast, CFD models can both compute and map the spatial distribution of WSS, establishing links between haemodynamic disturbance and atherogenesis and explaining why atherosclerotic plaque tends to be deposited at arterial bends or bifurcations.
CFD modelling has also been central to comprehending the role of WSS in endothelial homoeostasis. While turbulent blood flow reduces WSS and stimulates adverse vessel remodelling, non-disturbed laminar blood flow seems to be associated with higher WSS – which reduces endothelial cell activation. In a March 2012 issue of ‘Circulation’, researchers from  Johns Hopkins University School of Medicine, CVPath Institute at Maryland and the Mount Sinai School of Medicine in New York established that a complex series of WSS-related signalling pathways and interactions underlie the above phenomenon.
Though much more remains to be understood before such pathways can be exploited to their full extent to yield new anti-atherosclerotic therapies, few doubt that the way forward lies in further CFD models that combine dynamic fluid behaviour analysis with cellular response.

Other emerging techniques
Apart from CFD, other methodologies under consideration to quantify measurement of coronary plaque and lesions include the use of radio-frequency (RF) backscatter intravascular ultrasound. A prospective study in 2011 in the US known as ATLANTA sought to make the first-ever assessment of the accuracy of 3-dimensional, quantitative measurements of coronary plaque by computed tomography angiography (CTA) against intravascular ultrasound with radiofrequency backscatter analysis (IVUS/VH).
For the ATLANTA study, 60 patients underwent coronary X-ray angiography, IVUS/VH and coronary CTA. Plaque geometry and composition was quantified after spatial co-registration on segmental and slice-by-slice bases. The researchers found significant correlation for all pre-specified parameters by segmental and slice-by-slice analyses. Compositional analysis suggested that high-density non calcified plaque on CTA best correlated with fibrous tissue and low-density non calcified plaque correlated with necrotic core plus fibrofatty tissue by IVUS/VH.