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EmErgEncy mEdIcInE focus :Interpreting sT-segment elevation

Early identification of pre-eclampsia

optimised imaging protocols in fmIso PET

advances in ultrasound molecular imaging of inflammation

Printers for high quality medical images

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software to customise Qa in the X-ray room

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Equipment & Technology Medical ManagementVolume 37

March - April 2011

adhesive for use with neonates

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Awaited with per-haps not the bated breath associated with such trivia as Oscar nomina-tions or football World cup draws, the annual pub-

lication of the latest global cancer statistics is, nevertheless, a veritable gold-mine of data for all epidemiolo-gists, oncologists and public health professionals. After all, cancer is the leading cause of death in economi-cally developed countries and the second leading cause of death in developing countries, so the publica-tion (CA Cancer J Clin 2011; 61:00) of the latest statistics of worldwide estimates of cancer incidence and mortality produced by the Inter-national Agency for Research on Cancer (IARC) is of more than pass-ing interest. For those of us more focused on European statistics, the global data are complemented by the publication of European cancer mortality predictions for the year 2011 (Annals of Oncology 2011; 10: 1093). Inevitably of course, with the sheer volume of the information published, there is a danger of being overwhelmed in the details, but one doesn’t have to be an epidemiolo-gist or health statistician to grasp the main messages. To over-simplify, the good news is that the trend of total cancer mortality levels is downwards both for men and women while the bad news is that the absolute number of deaths is still enormous (7.6 mil-lion deaths world-wide per annum). Worse, largely because of the ageing and growing world population and despite the slight decrease in cancer rates, the overall global burden of cancer continues to increase. Beneath these stark headlines there are many other more detailed messages. For example, lung cancer in European women continues to rise inexorably (except in the UK where the inci-dence is more or less static, perhaps because the UK rates of female lung cancer have already been extremely high for a decade or so now). Glo-bally, female lung, breast and color-ectal cancers still occur in high frequencies and although overall cancer incidence rates in the devel-

oping world are roughly half of those in the developed world in both sexes, the overall cancer mortality rates are more or less similar. Some par-ticularly encouraging signs do exist, such as the downwards trend (most marked in the developed world) of cervical cancer presumably due to the impact of the HPV vaccination programmes. However to dampen any such grounds for optimism, the

terrible truth is that, despite decades of health education, a huge propor-tion of the overall cancer burden is due to the fact that, world-wide, there is an increasing adoption of cancer–causing behaviours. While research-based developments aimed at cancer prevention or cure (the best example so far is the HPV vac-cination case) are of course welcome, the hard reality is that, once again,

the IARC global statistics show that a substantial proportion of the awful impact of cancer could be reduced simply by modifying life style fac-tors such as eating healthily, stop-ping smoking and taking reasonable physical activity.

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ContentsfronT coVEr ProducTs[35] Printers for high

quality medical images

[36] software to cus-tomise QA in the X-ray room

[37] Adhesive for use with neonates

fEATurEs[6 - 13] EmErgEncy mEdIcInE

[6 - 9] Interpreting ST-segment elevation

[10 - 12] Psychological support improves outcome in critically ill patients

[14] TEchnology wATch A contact-free patient supervision system

[16 - 22] molEculAr ImAgIng

[16 - 18] Molecular imaging-based ultrasound for assessment of inflammation

[20 - 22] Optimised imaging protocols for enhanced contrast in FMISO PET

[24 - 33] womEn’s hEAlTh sPEcIAl

[26 - 28] Early identification of pre-eclampsia

[30 - 31] The success of a multidisciplinary breast and breast screening clinic

[32 - 33] Laser computed tomography of the breast

rEgulArs[3] Editor’s letter

[5] News in brief

[34 - 38] Product news

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Researchers predict nearly 1.3 million cancer deaths in Europe in 2011

There will be nearly 1.3 mil-lion deaths from cancer in Europe in 2011 according to predictions from a study pub-lished in the cancer journal, Annals of Oncology recently. The estimates, which have been reached after researchers used a new mathematical model for predicting cancer mortality for the first time in Europe, show a fall in overall cancer death rates for both men and women when compared to 2007. But they also highlight some areas of concern, particularly rising rates of lung cancer in women.Researchers from the University of Milan, Italy and the Centre Hospitalier Universitaire Vau-dois and University of Lausanne, Switzerland, used data on cancer deaths in the European Union for the period 1970-2007 to cal-culate rates of death each year and to identify trends which they used to predict death rates for 2011. They looked at over-all rates in the EU (the EU was defined as the 27 member states as of January 2007), and also individual rates in six major EU countries: France, Germany, Italy, Poland, Spain and the UK. They predicted there would be 1,281,466 cancer deaths in the EU in 2011 (721,252 men and 560,184 women), compared to 1,256,001 (703,872 men and 552,129 women) in 2007. When these figures are converted into world standardised rates per 100,000 of the population, this means there will be a fall from 153.8 per 100,000 to 142.8 per 100,000 in men, and from 90.7 to 85.3 in women – a drop of 7% in men and 6% in women – since 2007. However, the number of women dying from lung cancer is

increasing steadily everywhere apart from in the UK, which has had the highest rates in women for a decade and is now seeing a levelling off. In the EU as a whole, world stand-ardised death rates from lung cancer in women have gone up from 12.55 per 100,000 of the female population in 2007 to 13.12 in 2011. Lung cancer has overtaken breast cancer as the first cause of cancer death in Polish women, as well as in women from the UK. The number of women who will die from lung cancer this year in the UK is 15,632 (com-pared to 14,900 in 2007); this represents a slight drop in the death rate from 20.57 per 100,000 women in 2007 to 20.33 in 2011. In Poland, 6,343 women will die from lung cancer this year compared to 5,643 in 2007, and this repre-sents an increase in the death rate from 15.53 per 100,000 women to 16.60 in 2011. The overall downward trend in cancer death rates is driven mainly by falls in breast cancer mortality in women, and lung and colorectal cancer in men. Declines in mortality from other major cancers such as stomach, uterus, prostate and leukaemia are likely to be seen in 2011. A worrying increase in deaths from pancreatic can-cer in women, which had been observed in 2004, appears to have levelled off. The research-ers plan to repeat the study to predict cancer deaths for 2012. They believe that such predic-tions can help countries to plan their allocation of resources and strategies for preventing, treating and managing cancer.http://tinyurl.com/6z2zrpo

High blood pressure may be caused by a mutation in the adrenal glandHigh blood pressure may in some cases be caused by benign hormone-producing tumours of the adrenal cortex. A joint Swedish-American research effort has now uncovered a genetic cause behind the occur-rence of such tumours.

Approximately 5 % of patients with elevated blood pres-sure have benign endocrine tumours in their adrenal gland. The tumours produce abnor-mally high levels of the hor-mone aldosterone (the con-dition is known as primary aldosteronism), which in turn causes blood pressure to rise. Why the tumours arise has thus far been unknown.Researchers at the Endocrine Surgery Unit at the Department of Surgical Sciences at Uppsala University Hospital, Sweden in collaboration with colleagues at the Yale School of Medicine, USA, have now identified a

causal mechanism. The genetic codes of the relevant genes in tumour and normal tissue were analysed by means of exome sequencing, a new technique. The results showed that muta-tion in a specific potassium channel (KCNJ5) – which has a role in the passage of molecules into and out of cells – results, in a large number of cases, in tumour growth and overpro-duction of the hormone aldos-terone. This leads to increased levels of potassium and water in the blood, which raise the blood pressure. The same muta-tion turns out to underlie a rare genetic disease character-ised by a difficult-to-treat high blood pressure condition. The discovery may help to improve diagnostics in connection with primary aldosteronism and cases of severe blood pressure elevation. The mutated potas-sium channel also represents a potential target molecule for treatment of the tumours in question.http://tinyurl.com/6zo42ao

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6 EMErGENCy MEdiCiNE

The electrocardiogram is one of the most revolutionary inventions in the history of cardiophysiology, and the one for which Dr Willem Einthoven was awarded the Nobel Prize in Medicine in 1924 [1]. Since then, the easy availability, and the fast and inexpensive nature of the test, have made ECG a main-stay of the initial diagnostic work-up of all patients presenting to the emergency depart-ment (ED) with signs and symptoms sugges-tive of acute coronary syndrome (ACS), or with a myriad of other cardiac conditions. Abnormalities on an electrocardiogram (ECG) can be an early manifestation of ACS. In 2007, a new definition of MI was proposed by the joint European Society of Cardiology/American College of Cardiology Founda-tion/American Heart Association/World Heart Federation task force who defined MI as “evidence of myocardial necrosis in a clini-cal picture aligned with myocardial ischae-mia” [2]. According to this definition, new ST-T wave changes, a new left bundle branch block and the development of a pathological Q wave on ECG are considered to be evi-dence of myocardial ischaemia. Such ECG changes, together with the rise and/or fall of the level of relevant cardiac markers in a patient are suggestive of MI.

The ST-segment correlates with the pla-teau phase of myocardial repolarisation.

In a healthy myocardium, the ST-segment is isoelectric. An ischaemic injury second-ary to a decrease in perfusion results in the progressive decrease of levels of the high-energy molecule ATP in cardiac myocytes. Dysfunctional ATP-dependent pumps lead to loss of homeostasis and the resting mem-brane potential of the cardiac myocytes decreases with the shortening of the dura-tion of the action potential. This creates an energy gradient between the healthy and ischaemic myocardium leading to a current flow which alters the morphology of the ST-segment on the surface ECG. Such changes in the ST-segment depend on the extent of the ischaemic injury to the cardiac myocytes, the duration of the injury, the spatial orienta-tion of the particular ECG lead and the area involved, which in turn depends on the site of occlusion of the supplying coronary artery and the presence of collaterals. In order of appearance, the changes on the ECG include a hyperacute T-wave, an ST-segment devia-tion, changes in the QRS complex and t-wave inversion. A deviation of the ST-segment of more than the threshold value in more than two consecutive ECG leads is suggestive of myocardial ischaemia or infarction.

In 2009 the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society updated the stand-ardisation and interpretation of ECG [3] and in particular pointed out that threshold values for ST-segment deviation depend on age, gender and ECG leads. For example an elevation of the J-point (the junction of QRS complex and ST-segment) ≥2mm in V2 and V3 and ≥1mm in other leads is the threshold in men older than 40 years, whereas in men younger than 40 years of age the threshold is ≥2.5mm in V3 and V3. For women, the threshold ST-segment value is 1.5mm in V2 and V3, and 1mm in all the other leads. The threshold value for abnormal J-point depression is ≥0.5mm in leads V2 and V3,

and ≥1mm in all other leads, irrespective of age and gender. So-called reciprocal changes occur when there is a deviation of the ST-segment in any ECG lead accompanied by a deviation in the opposite direction in ECG leads directly opposite to the first lead. The amplitude of such reciprocal changes may not be identical as it depends on the distance of the recording lead from the ischaemic or infarcted area and axis of the primary lead.

Elevation of the ST-segment on ECG is most commonly the result of myocardial ischae-mia, infarction secondary to atherosclerotic stenosis or occlusion of coronary arteries. In current practice, almost all cases presenting to the emergency department with chest pain and ST-segment elevation on electrocardio-gram (ECG) are assumed to be suffering from atherosclerosis disease and reperfusion therapy is instituted. This is an acceptable practice considering the risk and benefits of management and the high mortality associ-ated with condition. Occasionally, there are patients admitted with ST-elevation who do not show obliteration of coronaries on angiography. The reported number of such cases is currently rising, possibly because of greater number of angiographic procedures being carried out. Such patients either have transient abnormalities, coronary anomalies or absolutely normal coronaries, conditions which could broadly be classified (see below) as either benign and not requiring any active management or serious-to-critical where their recognition is vital for further manage-ment. Table 1 summarises key ECG features and the management of conditions that could present with ST-segment elevation.

Benign conditionsOver 90% of healthy young men have up to 3 mm ST-elevation in one or more precor-dial leads, more often in lead V2 [4]. In such instances, the ST-segment is concave [Figure 1].

Normal variant or early repolarisation: In some members of adult male black popula-tions, an ST-elevation of 1 to 4 mm is seen in the mid-to-lateral precordial leads. ECG tracing shows a prominent J wave (notch or slur on the downsloping portion of the QRS complex), symmetric ST-elevation concord-ant with the QRS complex and a large ampli-tude positive T wave. Reciprocal changes may be present[5].

interpreting st- segment elevation in electrocardiogramsElevation of the st segment of the ECG is characteristic of myocardial infarc-tion but can also occur in many other conditions, often in the absence of any myocardial blood supply/demand problem. An awareness of such condi-tions is necessary for the appropriate management of the patient: this article briefly reviews the characteristics of cases where st-elevation can be seen.

by dr Vikas singh and dr subhash Chandra

– march/April 2011

Figure 1. Normal ST-segment elevation in the precordial leads, most prominent in leads V2

and V3, with concavity upwards.

7

Precordial lead: Misplacement of precor-dial leads (either too high or too low) can cause significant ST-T deviation [6]. A lead positioned even 2 cm too high can produce an ECG that mimics an anterior infarction. Lead misplacement should be suspected from inverted P waves in V1, V2 and V3.

Transthoracic cardioversion: Transient post-shock ST-segment elevation without any rise in the serum level of cardiac biomar-kers has been reported in up to 19% of patients who received transthoracic shocks [7, 8]; no evidence of cardiac damage has been found in such patients [9].

Serious-to-critical conditions1. Haemodynamically significant primary anomalies of the coronaries Several conditions can produce myocar-dial ischaemia/infarction: ostial stenosis or atresia, coronary artery fistula, anomalous origin of the left coronary artery from the pulmonary artery, a coronary artery from the opposite sinus (ACAOS) with intramu-ral course, and myocardial bridging [10]. Of these a pre-capillary fistula connecting a major coronary artery with the cardiac chamber or superior vena cava is the most common implying in most the existence of a left-to-right shunt [10]. An ACAOS is usu-ally asymptomatic or present with atypical chest-pain but some patients die at a young age after extreme exertion [11]. An anoma-lous origin of the left coronary artery (LCA) from the pulmonary artery always results in myocardial ischaemia.

Myocardial bridging (MB) is described as systolic narrowing of a coronary artery and is observed in at least one angiographic projection [12], with the degree of coro-nary artery compression by the myocardial bridge depending on the precise location of the artery, the thickness and length of the muscle bridge and the degree of cardiac con-tractility. It is commonly seen in the middle to distal part of the left anterior descending (LAD) artery [13]. Although by itself, this does not usually cause significant haemody-namic compromise to the myocardium, rare incidents of myocardial ischaemia have been reported in stress testing[14].

2. transient coronary abnormalities In situ thrombosis or embolisation with sub-sequent clot lysis and recanalisation. In situ thrombus formation in normal coro-naries is associated with hypercoagulability (Factor V Leiden), the use of oral contra-ceptives or oestrogen replacement therapy, cigarette smoking and excess of levels of lipoprotein(a) and type-1 plasminogen


Table 1. Key ECG features and management of conditions that could present with ST-segment elevation.

Conditions Characteristics for diagnosis Initial management/ management over view

Acute myocardial infarction New ST-elevation of ≥2mV in men and ≥1.5mV in women at the J point in two contiguous leads, Elevated segment has a plateau or shoulder or upsloping, Reciprocal changes seen, ST-elevation is usually limited one coronary artery supplied area.

STEMI pager activation, Immediate thrombolysis or percutaneous coronary intervention

Normal ST-elevation The ST-segment is concave, Limited to one or more precordial leads, more often in lead V2.

These are benign conditions and do not require treatment for the ST-elevation per se.

Normal variant or Early Repolarization

Prominent J wave (notch or slur on the downsloping portion of the QRS complex), Symmetric ST-elevation concordant with QRS complex, A large amplitude positive T waves, Reciprocal changes in aVR, More common in young athlete black population.

Precordial Lead Mispla-cement

Mimics an anterior infarction, Associated with inverted P waves in V1, V2 and V3

Transthoracic Cardioversion Transient, last only couple of minutes, Immediately after cardioversion.

Primary Anomalies of the Coronary Arteries • Ostial stenosis or atresia,• Fistula,• Origin of the LCA from the

pulmonary artery,• A coronary artery from

the opposite sinus with intramural course

ST-elevation on ECG do not match the infarct related artery or has a missing artery on angiography

“Do not bother to look for these innocent anomalies, but be prepared to recognize them as benign if one is accidentally found, typically at coronary angiography” - Dr. Paolo Angelini14

Myocardial Bridging Presentation is similar to AMI, In most cases, ST-segment changes limited to LAD distribution Q wave might present suggesting old infarctions.

First line of management - negative inotropic and chrono-tropic agents, Antiplatelet agents for risk prevention, Stents, minimally invasive coronary artery bypass grafting or surgical myotomy for refractory cases.

Transient Coronary Abnormalities In-situ thrombosis or emboli-zation with subsequent clot lysis and recanalization

Presentation is similar to AMI, History of hypercoagulable stage/ smoking

Risk of recurrent MI and death is comparable with significant coronary stenosis. Hence, should manage inline with CAD.

Coronary Artery Spasm or Variant Angina

Severe chest pain, which usually comes without physical effort Transient ST-elevation in absence of raise in serum cardiac biomarker levels

Nitrates and calcium channel blockers, Long term supplement of Mg and statins are proven protective, Refractory cases may need stent placement and defibrillator implantation for arrhythmic complications.

Systemic inflammatory condi-tions (SLE, RA, Wegener’s Granulomatosis etc.

Known history AMI as a first manifestation of these conditions too has been reported

Trial of immunosuppressive drugs is helpful in resolving acute ischemic event. Overall risk of AMI in future remains high

Conduction Abnormalities LBBB

ST- elevation of ≥1 mm which is concordant with the QRS complex (score 5); ST-depression of ≥1mm in lead V1, V2, or V3 (score 5); and ST-segment elevation of ≥5 mm that is discordant with the QRS complex

In absence of clinically significant cardiac disease, isolated LBBB does not decrease overall survival but increases the prevalence of cardiovascular disease

Wolf Parkinson White (WPW) syndrome

Transient ST-elevation in leads V1-V6, Q wave-T wave vector discordance.

With symptomatic arrhythmias - radiofrequency ablation. Choice of antiarrhythmics depends on type of arrhythmia.

Acute Pericarditis ST-elevation is concave upwards and diffuse covering more than one coronary artery supplied region and PR segment depression

Management of pericarditis is based on suspected etiology

Myocarditis ST-elevation is not limited to one coronary artery supplied area and Disproportionate elevation in serum cardiac markers compared to ST-elevation MRI detects the myocardial edema and the myocyte damage.

Differentiation from AMI is very crucial since use of thrombolytics and anticoagulants are very detrimental in myocarditis. Initial management of myocarditis is supportive focusing on hemodynamic stability.

Hyperkalemia ECG changes are progressive. ST-elevation reversible correction of hyperkalemia Tall, peaked and tented T wave as an initial findings.

Potentially life threatening medical emergency and needs immediate correction of extra potassium level by albuterol, insulin, and cation exchange resin

Brugada Syndrome The ST-elevation is primarily seen in leads V1 and V2, ST segment begins from the top of R’ wave, is downs-loping, and ends with inverted T wave

Amiodarone is most commonly used antiarrhythmic but only implantable cardioverter-defibrillator is successful in preventing sudden deaths.

Pulmonary Embolism ST-elevation was limited to V1-V3 Clinical history and use of cardiac ultrasound are helpful in differentiation of these subjects from true AMI

Early thrombolysis is life potentially saving.

Head Injury and Intracranial hemorrhage

Can mimic AMI on ECG, echocardiographic and cardiac biomarker level

Before starting thrombolytics for AMI, intracranial hemor-rhage should be ruled out cautiously.

Takotsubo Cardiomyopathy ST-elevation associated with prolonged QT interval and deep precordial or global T-wave inversion on serial ECGs. Minimal elevation of cardiac biomarkers despite of large area of akinesis/dyskinesis seen on echocardiography.

In case of suspicion, case should be managed like AMI and once the diagnosis of TC is established, management is mainly supportive.

Scorpion Envenomation Syndrome

ST segment elevation mimics AMI Presents with history of scorpion bite, vomiting, sever pain at bite site and profuse sweating.

Prazosin to combat the autonomic storm.

Ventricular Aneurysm Persistent ST segment elevation and pathologic Q wave, Usually limited to leads I, aVl, and V1 through V6 due to the common location of aneurysm.

Medical management of complications and surgical correction of aneurysm


activator inhibitor. The risk of recurrent MI and death is comparable to that of patients with significant coronary ste-nosis [15]. Embolisation of the coronaries is theoretically possible and more common in the left coronary due to the preferential flow.

Coronary Artery Spasm (CAS) or “variant angina” is a tem-porary increase in coronary vascular tone (vasospasm) of an epicardial artery, causing a marked but transient reduc-tion in the luminal diameter. Sometimes thought to be sec-ondary to endothelial dys-function, this coronary vasos-pastic state is usually focal and can occur in either a normal or diseased vessel [16]. CAS is associated with cigarette smoking, marijuana smoking, alcohol intake, butane inha-lation, cocaine abuse, pseu-doephedrine, calcium channel blockers withdrawal etc. [17]. Early atherosclerotic lesions can predispose coronaries for

vasospasm, which is associated with transient ST-segment elevation in the absence of an increase in serum cardiac biomarker levels.

Endothelial dysfunction Detected by an impairment of the acetylcholine-induced vaso-constrictor response, endothe-lial dysfunction of the epicar-dial coronary arteries has been advanced as an independent AMI mechanism with normal coronaries and without appar-ent arterial spasm [18]. The altered local milieu of various vasoactive entities secondary to the dysfunction is believed to promote occlusion in the absence of any underlying sten-otic lesion [18]. The prognosis in these groups of patients is variable but in general better than those with atherosclerotic MI [19].

3. Conduction abnormalities The left bundle branch block (LBBB) and Wolf Parkinson White (WPW) syndrome are

common conduction abnor-malities where ST-segment elevation does not always indi-cate myocardial infarction. In a left bundle branch block (LBBB) an abnormal ven-tricular depolarisation leads to secondary alteration in the recovery process. This appears on the ECG as repolarisa-tion changes in a direction opposite to that of the main QRS-deflection (the so-called “appropriate discordance” between the QRS complex and the ST-segment) and produces a predominantly negative QRS complex with ST-segment elevation and positive T waves (an appearance similar to that of anterior AMI). Sgarbossa criteria are widely accepted for the differentiation of an ST-segment elevation of ≥1mm which is concordant with the QRS complex (score 5); an ST-segment depression of ≥1mm in lead V1, V2, or V3 (score 5); and an ST-segment elevation of ≥5 mm that is discordant with the QRS complex (score 2) [20].

Although ST-segment eleva-tion is rare in WPW syndrome, transient ST-elevation has also been described in leads V1-V6 [21]. In the majority (up to 94%) of such cases, a charac-teristic “Q wave-T wave vector discordance” is present where positive or iso-electric T waves are seen with the inferior lead Q waves, in contrast to the T wave inversion expected in cases of ischaemic injury [22].

4. Acute pericarditis and myocarditisIn acute pericarditis, the ST-segment elevation is diffuse, concave upwards and associ-ated with PR segment depres-sion although this is not specific to pericarditis. The ratio of the amplitude of the onset of the ST-segment to the amplitude of the T wave in lead V6 has been put forward as being the most reliable discriminator between pericarditis and normal [23]. The ST-segment elevation in both pericarditis and myocar-ditis is not limited to any area supplied by a particular coro-nary artery; there is a dispro-portionate elevation in the level of serum cardiac markers.

5. HyperkalaemiaECG changes in hyperkalae-mia are progressive: the earli-est changes are tall, symmetri-cally peaked, and tented T waves, followed by a decrease in amplitude of the P wave and a widening of the QRS as the serum concentration of potas-sium increases. Even though ST-segment elevation is not common, a few case reports have been published where the ST-segment has closely mimicked AMI [24]. The tall T waves of hyperacute ischaemic changes are usually associated with a long QT interval, and the T waves are broad rather than narrow.

6. Brugada syndromeThis is an inherited cardiac dis-ease causing life-threatening


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Figure 2. ST and T wave changes on serial ECG in Takotsubo Cardiomyopathy.

9

ventricular tachyarrhythmias in individuals with structurally normal hearts and character-istic ECGs. The ST- segment elevation is primarily seen in leads V1 and V2 and can have a “saddle back” shape, but in typi-cal cases the ST segment begins from the top of the R’ wave, is downsloping, and ends with an inverted T wave. This pattern is so distinctive that it should not be mistaken for an acute antero-septal MI complicated with RBBB where the down stroke of the R’ wave and ST segment have a distinct transition [25].

7. Neurological conditionsThe incidence of ST-segment elevations in cases of subarach-noid haemorrhage (SAH) has been reported as 7.5% to 31% [26]. A putative explanation is that the altered autonomic tone affects the duration of ventricu-lar repolarisation, and so pro-duces the changes which are not found to be associated with myocardial injury or increased mortality risk [9].

8. transient Left Ventricular Apical Ballooning syndrome or takotsubo Cardiomyopa-thy (tC)TC is characterised by transient wall-motion abnormalities involving the left ventricular apex and the mid-ventricle in the absence of obstructive epi-cardial coronary artery disease. ST-segment elevation has been reported in up to 11% of TC patients [27], [ Figure 2]. The unique pattern of left ventricu-lar dysfunction is characterised by apical and mid-ventricular contractile abnormalities with sparing of the basal segments. The minimal elevation of car-diac enzymes despite large focal akinesis is suggestive of TC [27].

9. Ventricular aneurysmThis produces persistent ST-segment elevation and patho-logic Q waves. In these cases ST-elevation is usually limited to leads I, aVl, and V1 to V6 due to the most common loca-tion of the aneurysm formation,

but ST-elevation is also seen in inferior leads in cases of inferior wall aneurysm. The morphology of ST-elevation is variable, and ranges from min-imally elevated and concave to the ominously significant convex elevation [28]. Another associated ECG finding seen in such cases is the loss of R wave deflection in precordial leads.

other rare occurrencesVery occasionally, ST-segment elevation can be seen in patients with massive pulmonary embo-lism and scorpion envenoma-tion syndrome, and vasculitis (systematic lupus erythemato-sus, Wegener’s granulomatosis and rheumatoid arthritis) [29], [34]. Due to their rarity, there is no consensus on the charac-teristic morphology of ST-seg-ment elevation in such cases.

Conclusion All of the conditions described in the current clinical review can electrocardiographically mimic ST elevation MI in one way or another, and frequently do so in the absence of any myocardial demand-supply abnormality. An awareness of all these con-ditions and their characteristic features is vital for appropriate patient management. Though occasionally it can be extremely difficult to distinguish some of these conditions from others, it is hoped that a brief review of the pathologies as presented here should be helpful to internists and emergency medi-cine physicians.

References1. Cooper JK. N Engl J Med

1986;315: 461.2. Thygesen K et al. Circulation

2007;116: 2634.3. Wagner GS et al. Circulation

2009;119: e262.4. Surawicz B et al. J of the American

College of Cardiology 2002;40: 1870.5. Klatsky AL et al. The Am J of Medi-

cine 2003;115: 171.6. Marafioti V et al. Am J of Emer-

gency Medicine 2004;22: 62.7. Van Gelder IC et al. Am Heart J

1991;121: 51.8. Kok LC et al. Am J of Cardiology

85: 878.9. Vikenes K et al. Am Heart J

2000;140: 690.10. Levin DC et al. Circulation

1978;58: 25.11. Angelini P. Circulation 2007;115:

1296.12. Bourassa MG et al. J of the Am Col-

lege of Cardiology 2003;41: 351.13. Cay S et al. Anadolu Kardiyol

Derg 2006;6: 9.14. Soran O et al. Tokai J of Experi-

mental & Clinical Medicine 2000;25: 57.

15. Kereiakes DJ et al. J of the Am Col-lege of Cardiology 1991;17: 304.

16. Ginsburg R et al. Western J of Medicine 1982;136: 398.

17. El Menyar AA. J of Postgrad Med 2006;52: 51.

18. Sztajzel J et al. Postgraduate Medi-cal J 2000;76: 16.

19. Raymond R et al. J Am Coll Cardi-ology l1988;11: 471.

20. Sgarbossa EB et al. [erratum appears in N Engl J Med 1996 Apr 4;334(14):931]. N Engl J Med l1996;334: 481.

21. Guler N et al. Angiology 2001;52: 293. 22. Khan IA et al. Am J of Emergency

Medicine 2000;18: 807.23. Ginzton LE et al. Circulation

1982;65: 1004.24. Sims DB et al. Circulation

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Medicine 2006;73: 627.26. Kawasaki T et al. Circulation J

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gency Medicine 2002;20: 238.29. Lin JF et al. Circ J 2009;73: 1157.34. Korkmaz C et al. Lupus 2007;16: 289.

The authorsVikas Singh1, Subhash Chandra2*1 Department of Medicine, Uni. of Pittsburgh Medical Center, Pittsburgh, PA, USA.2 Department of Emergency Medicine, Mayo Clinic, Roches-ter, MN-55902, USA

*Corresponding author: Subhash ChandraDept of Emergency Medicine, Mayo Clinic, Rochester, MN-55902, USATel. +1-507-293-0794e-mail: [email protected]


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Critically ill individuals suffer high levels of stress and intense adverse emotions, ranging from fear, anxiety, agony, lone-liness, depersonalisation, hopelessness, bewilderment and acute confusion, to ter-ror attacks and panic [1]. With its ensuing progressive organ dysfunction that may lead to sepsis and vital organ failure, criti-cal illness is itself a state of uncompensated stress with physiological and psychologi-cal correlates. Although through use of sophisticated life support technology we can sustain vital functions, there is almost nothing we can do to counteract the effects of stress on the cell. Stress is a key factor in critical illness, since it may be the cellular response to stress that shapes the trajectory of disease and may lead to the development of one of the most fatal syn-dromes, the multiple organ dysfunction syndrome (MODS) [2]. Although psycho-logical stress has long been recognised as a

factor in disease, the potential organismic effects of stress and the means to alleviate them have not received enough attention in critical care.

Evidence on the effect of mind-body interventions, together with the often expressed need of families and patients for psychological support intervention, have fuelled new interest for the explo-ration of the effects of stress in critical illness [3]. This paper aims to present research evidence on the effects of psy-chological support, including guided imagery and relaxation, on the psycho-logical and physiological outcomes of intensive care patients. A narrative criti-cal review methodology of published studies involving adult intensive care patients was used. Databases searched included Medline, CINAHL, PubMed, PsychInfo and the Cochrane Library.

Relaxation response versus stress response in critical illnessA large body of evidence suggests that stress and molecules, such as neuropeptides and cytokines involved in stress, may contribute to the pathophysiology prevalent in critical illness, including systemic inflammation [4], cellular stress and oxidative damage [5], endothelial dysfunction and coagulopa-thies [6], which account for high mortality and morbidity. On the other hand, positive affective states, such as hope and relaxation may reverse these adverse consequences [7]. The relaxation response may be viewed as the opposite of the stress response. It is an integrated psycho-physiological reac-tion, primarily elicited by hypothalamic and limbic system sites [8], and mediated by the vagus nerve and cholinergic neurotransmis-sion. It leads to reduction of sympathetic activity, thus reversing the effects of stress on the body, including counterbalancing of negative emotions, and decreased oxygen consumption, blood pressure, heart rate and rate of respiration [9,10]. Even more impor-tantly, recent evidence shows that relaxation may interrupt the inflammatory vicious cir-cle of critical illness. Activity of the vagus nerve, such as is involved in relaxation, may prevent tissue injury and death in animal models of sepsis, ischaemia/reperfusion and haemorrhagic shock [11,12]. Moreover, pharmacologic cholinesterase inhibition, which accentuates vagus neurotransmis-sion, increases survival in mice with severe

Psychological support improves outcomes of critically ill patientsBecause of the hormonal, inflammatory and neuroendocrine responses they elicit, stress and negative emotions are potent pathogenetic factors in criti-cal illness and are linked to increased morbidity and mortality. research evidence shows that psychological support intervention, including guided relaxation and imagery techniques, can result in significant improvements in patient outcomes, vital signs and decrease pain, anxiety, complications and length of stay. therefore, support interventions in critical care need to be investigated and in future should be vigorously implemented.

by dr Elizabeth d.E. Papathanassoglou


11

sepsis [13], and activation of the cholinergic anti-inflammatory pathway protects against toxin-induced organ failure [14]. Activity of the vagus nerve may be stimulated via bed-side techniques such as relaxation, imagery and biofeedback. A recent critical review documented an association between guided imagery/relaxation and the functioning of the immune system [15]. Relaxation has been reported to elicit specific gene-expression changes [16]. It may therefore be appropriate and timely to overcome per-spective and culture barriers and examine such interventions more actively.

Effectiveness of psychological sup-port interventions in critical illnessIn critical care, supportive clinician-patient relationships are deemed very important [17]. Research has identified specific sup-portive interventions, such as the providing of explanations, giving advice, reassuring and raising faith and hope, cheering-up, strengthening patients’ self- esteem, giv-ing emotional warmth, offering empathetic listening, presence, emotional care, speak-ing calmly, empathetic touch and spending extra time with patients [18]. Imagery and relaxation may be viewed as a means of psy-chological support since they encompass supportive nurse-patient interactions, and they may raise hope and positive emotions.

relaxation studiesThe evidence provided by relaxation and guided imagery studies is quite compelling. Overall, in all intervention studies involv-ing approximately 15 or more patients per group, significant improvements in physi-ological and psychological measurements were observed [Table 1].

In an early experimental study with acute myocardial infarction patients, Guzzetta [19] showed that there were improved vital signs and a lower rate of complications in patients randomised to a relaxation inter-vention based on Benson’s method [20], compared to a standard care group. Notably, despite the short relaxation training, cumu-lative effects over time were seen, which may imply that the relaxation response persists, and/or that, with practice, patients become more proficient in eliciting the response.

Miller and Perry [21] tested the effects of a relaxation technique based on slow deep breathing on the postoperative pain of 15 coronary artery by-pass graft (CABG) patients. Significant decreases were demon-strated in blood pressure, heart rate, respi-ratory rate and pain ratings. Nonetheless, the validity of these results is limited by the

lack of random assignment in the study. In another small experimental study, 25 cardiac surgery patients were randomised to either foot massage or relaxation or to a control group [22]. Only a non-signif-icant trend for decreased anxiety in the relaxation group was observed.

Two studies explored the impact of relax-ation on sleep quality. Richardson showed that autogenic relaxation combined with imagery improved patients’ sleep [23]. Remarkably, men responded immediately, while in women the improvement was delayed. This may suggest that gender, as


Table 1. Psychosocial intervention studies in intensive care (ARDS: adult respiratory distress syndrome; CABG: coronary artery by-pass graft; PTSD: post-traumatic stress disorder).

Authors/ year

Type of study -main Intervention

Patients main Physiological outcomes

relaxation Techniques

1. Guzzetta, 1989

Randomized controlled trial- Guided relaxation & music therapy

80 coronary care patients randomized into two intervention and one control group

Lowered heart rate, lowered temperature and decreased cardiac complications in both relaxation and music therapy groups. Increased patient satisfaction with intervention.

2. Miller & Perry, 1990

Pre- & post-test quasi-experi-mental study-Deep-breathing relaxation technique

Convenience sample of 29 cardiac surgery patients

Lowered blood pressure, heart rate, respiratory rate and pain

3. Hattan et al., 2002

Pre- & post-test experimental study -Guided relaxation or foot massage

25 cardiac surgery patients randomized to either one of two intervention groups or to a control group

No significant differences between physiological parameters. A trend for higher levels of calm in the relaxation group.

4. Richards, 1998

Experimental design- 6-mi-nute back massage or relaxation audiotape

69 older ICU patients with a cardiovascular illness

Significant improvement of sleep quality measured by polysomnogra-phy between the back-massage and control group

5. Richardson, 2003

Experimental design-Relaxa-tion and imagery

38 critically ill randomized into two groups to determine the ef-fects of relaxation and imagery on sleep

Improved subjective quality of sleep

6. Friesner et al., 2006

Pre- & post-test quasi-expe-rimental study- Slow deep-breathing relaxation

40 CABG patients during chest tube removal

Decreased pain ratings immediately after and 15 minutes post chest tube removal

7. Houston & Jesurum, 1999

Quasi-experimental study- Quick relaxation

24 CABG patients during chest tube removal

No significant decrease in pain ratings immediately after and 30 minutes post chest tube removal. Trend for decreased pain in older male patients, and for increased pain in older female patients.

Imagery Techniques

8. Tusek et al., 1999

Randomized controlled trial- Guided imagery

65 cardiac surgery patients randomized into one interven-tion and one control group

Decreased pain & length of stay

9. Deisch et al., 2000

Quasi-experimental prospective study -Guided imagery

Convenience sample of 100 Cardiac surgery patients

Reduced pain, fatigue, narcotic use and decreased length of stay

10. Halpin et al., 2002

Retrospective review of pa-tient data- Guided Imagery with music

134 non-randomized critically ill patients having participated in guided imagery compared to 655 normal care patients.

Decreased length of stay Decrease in required pain medica-tion not statistically significant.

Interaction with health care Professionals

11. Hwang et al., 1998

Prospective randomized study- Tape-recorded mes-sage from physician

Convenience sample of 60 post-operative cardiac surgery patients

Increased peripheral temperature, decreased pain, tension, anxiety and depression. Patient expressed a high need for this support program.

12. Bergmann et al., 2001

Prospective randomized study- Preoperative exten-sive information & personal attention from surgeon

Convenience sample of 60 patients undergoing cardiac surgery

No effects on the perioperative psychoendocrinologic course of stress (plasma & salivary cortisol and anxiety reports).

13. Henneman, 1989

Prospective randomized study- Touch and verbal interaction

24 mechanically ventilated patients randomized to one intervention and one control group

No differences in heart rate, arte-rial pressure, and respiratory rate

long-term effects of psychosocial support

14. Deja et al., 2006

Prospective correlational study to explore the effect of recalled social support while in the ICU

65 ARDS survivors Perceived social support was associated with a reduction in PTSD symptoms and improved health-related quality of life.

13

well as time, must be taken into consid-eration in relaxation studies. Richards also explored support interventions for the improvement of sleep and found no significant effects [24].

In two quasi-experimental studies the effect of relaxation on pain as an adjunct to opioid therapy was tested during chest tube removal in coronary artery by-pass graft (CABG) patients. Friesner et al reported that slow deep-breathing relaxa-tion accounted for significantly decreased pain ratings [25]. However an earlier study showed no significant effect of a quick relaxation technique on pain during chest tube removal [26].

Guided imagery studiesThree studies have been carried out on the effects of guided imagery in ICU patients. Tusek et al. showed that pain ratings and length of stay decreased in cardiac patients randomised to a guided imagery interven-tion administered via an audio tape [27]. Deisch et al. replicated Tusek’s study with 100 patients undergoing CABG and found reduced pain, anxiety, fatigue, narcotic usage and length of stay and increased patient sat-isfaction in the experimental group [28].

A retrospective data review of 134 patients one year after the implementation of guided imagery found that length of stay was shorter, pharmacy and pain medication costs were decreased, while high overall patient satisfaction was maintained [29].

Clinician-patient interaction studiesIn an experimental study involving cardiac surgery patients [30], the mere fact of listen-ing to a physician’s tape-recorded message providing information and emotional sup-port was found to give rise to effects similar to those of Guzzetta [19] in terms of periph-eral vasodilation — but not of heart rate — as well as a decrease in pain, tension, anxi-ety and depression. In a subsequent study of cardiac surgery patients, no effect on patient stress of preoperative oral information com-bined with more personal attention by the surgeon was observed [31].

Henneman carried out a prospective ran-domised study to determine the effect of direct nursing contact on the stress of patients being weaned from mechanical ventilation [32]. Twenty-six patients were randomly assigned either to an experimental group involving touch and verbal interaction during the weaning, or to a control group. No significant differences were observed in heart rate, respiratory rate and mean arterial

pressure; however, the power of this study was limited due to the small sample size.

social support studiesAt a prospective correlational study on the influence of perceived social support dur-ing ICU treatment on the quality of life in 65 survivors of acute respiratory dis-tress syndrome (ARDS), it was found that increased perceived social support was associated with a reduction in symptoms of post traumatic stress disorder [33]. The authors concluded that social support from family members might improve coping in critically ill individuals.

ConclusionAlthough the literature describing the effects of supportive psychological support interac-tion on the outcomes of critically ill patients is limited, there is evidence that imagery and relaxation techniques, as well as psy-chosocial support in the ICU, are linked to improved short- and long-term patient out-comes. More research is needed to evaluate the effect of planned emotional support by nurses on patient outcomes, both through randomised and interpretively designed clinical trials. Issues of gender, diagnoses, as well as the effect of time on outcomes should be taken into account in such trials.

References1. Lusk B et al. Dimensions of Critical Care Nursing

2005; 24:25.

2. Papathanassoglou E et al. Nursing in Critical Care 2009;15:204.

3. Mellott KG et al. J of Holistic Nursing 2008; 26:128.

4. Elenkov IJ et al. Pharmacological Reviews 2000; 52:595.

5. Sobocanec S et al. Physiological Research 2005; 54:97.

6. Nemccsik J et al. Eur J of Pharmacology 2004; 498:195.

7. Gitto E et al. Pediatric Research 2001; 50:756.8. Jacobs GD. J of Alternative and Complementary

Medicine 2001;7 Suppl 1:S83.9. Friesner SA et al. C. Heart Lung 2006; 35:269. 10. Mandle CL et al. J of Cardiovascular Nursing

1996; 10(3):4. 11. Oke SL et al. J of Leukocyte Biology 2007;

83:512. 12. Huston JM et al. Critical Care Medicine 2007;

35:2762.13. Hofer S et al. Critical Care Medicine 2008; 36:

404. 14. Mabley JG et al. Molecular Medicine 2009 Feb

11. 15. Trakhtenberg EC. Int J of Neuroscience 2008;

118:839.16. Dusek JA et al. PLoS ONE 2008; 3:e2576.17. Wilkin K et al. J of Clinical Nursing 2004;13:50.18. Frazier SK et al. Am J of Critical Care 2003;

12:19.19. Guzzetta CE. Heart Lung 1989;18:609.20. Bagheri-Nesami M et al. Int J of Nursing Prac-

tice 2006; 12:214.21. Miller KM, Perry PA. Heart Lung 1990; 19:136.22. Hattan J et al. J of Advanced Nursing 2002;

37:199.23. Richardson S. Dimensions of Critical Care

Nursing 2003; 22:182.24. Richards KC. Am J of Critical Care 1998;7:288.25. Friesner SA et al. Heart Lung 2006; 35:269. 26. Houston S et al. Applied Nursing Research

1999;12:196.27. Tusek DL et al. J of Cardiovascular Management

1999; 10:22.28. Deisch P et al. Nursing Clinics of North Amer-

ica 2000; 35:417. 29. Halpin LS et al. Outcomes Management 2000;

6:132.30. Hwang SL et al. J of the Formosan Medical

Association 1998; 97:191.31. Bergmann P et al. Anesthesia & Analgesia 2001;

93:1093.32. Henneman EA. Heart Lung 1989;18:483.33. Deja M et al. Critical Care 2006;10:R147

The authorElizabeth D.E. Papathanassoglou, PhD, MSc, RNAssociate Professor Intensive Care NursingCyprus University of TechnologyLimassol, Cyprus e-mail: [email protected]


It has been shown that pain ratings and length of hospital stay are decreased in cardiac

patients who received guided imagery interven-tion administered via an audio tape [27].

EMErGENCy MEdiCiNE

14 tECHNoLoGy WAtCH

A significant number of avoidable adverse and sentinel events occur on the general care floor, where nurse-to-patient ratios often prevent continuous direct patient observation. Numerous studies have shown that many of the patients that suf-fer serious deterioration in their condition or sudden death have preceding predictive events. Thus, monitoring of vital signs may improve prediction of deterioration as well as improve patient outcome.

Designed specifically to address patient care, safety and quality issues in the envi-ronment of the medical-surgical unit, the EverOn Bed-side units and Central Dis-play Station (CDS) enable continuous supervision of patients where nurse-to-patient ratios prevent continuous patient observations. The system also transfers alerts directly to the nurse’s cell phone or pager. Setup is rapid and flexible. All mon-itoring is performed without direct con-tact between the patient and the device, using a sensor that is placed under the mattress. Staff can easily adjust thresholds for alerts utilising the user-friendly touch screen. The system produces a low rate of false alerts, and parameters and alerts can be easily customised per patient. The information stored in the display unit can be accessed at any time and reports can be printed for off-line documentation and review. The flexibility and user-friendli-ness of the system and its Central Display

station allow easy integration with the current nurse work flows.The system provides continuous surveil-lance of several parameters, including heart rate, respiratory rate and movement rate of the patients. Alerts are given if any of the parameters exceed predefined thresholds set by the clinicians. A bed exit alert is provided for high risk patients such as those at risk of a fall. The system also includes a display that alerts medi-cal staff regarding a patient’s motion level and verifies patient turns as indicated by nurses, helping to prevent the develop-ment of pressure ulcers. The Central Dis-play Station displays live updates from up to 36 bedside monitors on large screens placed at the nurse station and the unit walls so clinicians can see updates in real time as they walk by the displays. In addi-tion, alerts can be transferred to nurses’ mobile phones or pagers.

Multi-centre studyA multi-centre study was conducted at several hospitals in the US and Israel to evaluate the correlation between the dif-ferent parameters measured by the EverOn system and the detection of patient dete-rioration in hospitals. More than 200 patients were monitored on the medical/surgical floors of three medical centres with the EverOn system. The results show that by combining the measurements of respiratory rate, heart rate and a new res-piratory pattern alert called Double Respi-ration Pattern (DRP, characterised by two

unequal sections in each single respiration cycle), patients who are likely to deterio-rate are effectively identified. A risk factor of 12.2 was shown for major patient dete-riorations, i.e. there was a dramatic 12.2 times greater chance of a major deteriora-tion in patients where the system alerted versus patients where it didn’t.

Improved outcomes and reduced costsThe EverOn Patient Monitoring System was evaluated by a team of clinicians at a com-munity hospital in California, USA. The hospital selected a 33-bed, medical-surgical unit for the study, and included general medical, trauma and post-surgical patients. To establish a control level, patients’ out-come variables including patients’ length of stay, total ICU days, number of falls and in-hospital-developed pressure ulcers were reviewed for six months. EverOn was then introduced to the same unit and was used to monitor every patient admitted for the subsequent six months. The study evalu-ated patient outcomes before and after introduction of the system.

Overall positive nursing satisfaction results were associated with acceptable level of alert frequency and overall ease of use with the system. The decrease in the average length of stay in the hospital and the total “higher level of care days” had a positive impact on the cost of patient care. Particularly significant was the decrease in the development of pressure ulcers, a preventable hospital complication. The incidence of falls also trended downward, but did not reach statistical significance. Actionable alerts at the bedside led nurses to take immediate clinical actions for dangerous conditions that would have otherwise have gone unnoticed.

In conclusion, the implementation of EverOn on a Medical/Surgical unit resulted in measurable improvements in patient care and safety, nursing accept-ance and reduced costs. The system is currently installed at several medical cen-tres in the USA and Europe.

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Contact-free patient supervision system detects hospitalised patient deteriorationCritical events such as cardiopulmonary and respiratory events are estimated to occur in 4% to 17% of in-patient admissions. A significant number of these events are preceded by warning signs. Based on a non-contact piezoelectric sensor placed underneath the patient’s mattress, an innovative system, the Everon, meas-ures respiration and heart rates as well as bed movements. the system provides clinicians with a valuable tool for timely recognition of vital sign deterioration.


Central display station at nurse’s station.

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16 – march/April 2011

Medical ultrasound has long been used in clinical applications both as a primary modal-ity and as a supplement to other diagnostic procedures. The basis for ultrasound imag-ing is the transmission of high frequency (megaHertz) sound waves that propagate through tissue. These sound waves back-scatter from the interfaces between tissue components with different acoustic proper-ties and are detected by the imaging system, allowing the creation of images based on tis-sue characteristics and spatial location. Thus, traditional ultrasound has focused primarily on the imaging of anatomical structures and analysis of blood flow in large vessels. Until recently, there has been no mechanism by which ultrasound has been able to detect changes at the cellular and molecular level.

Molecular imaging is a broad term for describing a technique designed to evaluate cellular and molecular activity in biological systems [1, 2]. Traditionally, the modalities associated with molecular imaging have been positron emission tomography (PET), single-photon emission computed tomog-raphy (SPECT) and optical imaging. How-ever, in recent years, ultrasound has gained interest in the area of molecular imaging due to the practical advantages over these other imaging modalities: it is inexpen-sive, safe (no ionising radiation), portable and readily available with fast acquisition times [1, 2].

The principle behind ultrasonic molecular imaging is the selective targeting of acous-tically active intravascular microbubbles to biomarkers expressed on the endothe-lium [Figure 1], [1-3]. Once accumu-lated at the target site, the microbubbles enhance the acoustic backscatter from

pathologic tissue that might otherwise be difficult to distinguish from normal tis-sues. Since ultrasonic molecular imaging has the potential to provide information prior to the appearance of phenotypic changes, it is proposed that this method can facilitate early assessment of disease progression or response to therapy [1]. Preclinical imaging studies have demon-strated the efficacy of ultrasonic molecu-lar imaging for applications including, assessment of tumour angiogenesis, the diagnosis of myocarditis, the evaluation of transplant rejection, the evaluation of cardiovascular disease and imaging dys-functional endothelium, thrombus and inflammation [2, 3]. This article sum-marises the basics of ultrasonic molecu-lar imaging, recent developments and future directions as we progress towards clinical relevance.

Targeted contrast agentsContrast agents being studied for ultra-sonic molecular imaging applications include emulsion nanoparticles, echogenic liposomes and microbubbles [1, 4]. How-ever, microbubbles are the most common agent used in this imaging modality due to their high echogenicity and their non-linear response to ultrasonic stimuli [1, 5]. Targeted microbubble contrast agents are similar to microbubbles used for perfusion imaging contrast agents in that they are composed of a gas core and are usually sta-bilised by a lipid, protein or polymer shell [4]. The lining of the gas core is usually of a high molecular weight to limit the diffu-sion of the gas out of the bubble for longer persistence times [4]. Unlike perfusion agents, contrast agents for molecular imag-ing incorporate high-affinity adhesion lig-ands (such as an antibody, peptide etc.) into their shell, which is specific for a particular disease epitope [4].

The mismatch in acoustic impedance (a function of an object’s density and com-pressibility) between the microbubble gas core and blood (or tissue) is several orders of magnitude, resulting in substantially higher scattering from a bubble than an equivalent volume of tissue or blood. Addi-tionally, microbubbles oscillate in response to an ultrasonic field, and respond non-linearly to acoustic pulses even at low ener-gies, unlike tissue [1]. The non-linear prop-erty of microbubbles in an ultrasound field allows for the use of various pulsing and signal processing strategies to detect the backscattered signal from contrast agents and segment it from tissue, thus providing a high contrast-to-noise ratio [1]. Due to these unique acoustic properties, a clinical ultrasound system can detect even single microbubble contrast agents, providing exquisite sensitivity.

One limitation to this type of agent is that because of their size (typically between 1 and 10 microns in diameter), they are confined to the vascular space [2]. There-fore, microbubbles are unable to target extravascular cell receptors. Another significant limitation of microbubble

Molecular imaging with ultrasound: a burgeoning technology for inflammation assessmentUltrasound is a favoured clinical imaging modality due to its convenience, low cost, high frame-rate capability, and safety. Although traditional ultra-sound is primarily an anatomical imaging modality, recent studies have demonstrated the potential for ultrasound as a molecular imaging technique through the use of intravascular contrast agents targeted to specific cell receptors of disease.

by dr Jason E. streeter and dr Paul A. dayton

Figure 1. Molecular imaging concept cartoon: Endothelial cells express biomarkers correlated

with pathology. Targeted microbubble agents in the vascular space adhere to the biomarkers, pro-viding image contrast during an ultrasound exam.

CoVEr story

17 – march/April 2011MoLECULAr iMAGiNG

contrast agents is that they have relatively short life spans (in the order of minutes), which prohibits long-term tar-geting applications such as the tracking of labelled cells in cell therapy applications [2].

Molecular imaging of inflammationNoninvasive assessment of inflammatory markers is one of the more promising applica-tions of ultrasonic molecular imaging. Inflammation plays an important role in most cardio-vascular diseases [2, 3]. Since traditional ultrasound methods do little to quantify the mecha-nisms of inflammation, the ext-sitence of a noninvasive imag-ing method, such as ultrasonic molecular imaging, would be invaluable as a diagnostic test, and in evaluation of response to therapy applications. In recent years, microbubbles have been shown to target either acti-vated leucocytes or endothelial cell receptors that are upregu-lated during inflammation [2]. These methods have allowed significant progress to be made in identifying inflamma-tory response in such fields as assessing reperfused myocar-dial infarction, atherosclerosis, intraplaque neovascularisation from the vasa vasorum, trans-plant rejection and ischaemic memory [2, 3, 6-8].

Reperfusion InjuryCurrently, there is no optimal clinical method that is capable of quantifying the postischae-mic inflammatory response of the immune system after reperfusion of the myocardial infarct [3]. By using micro-bubbles targeted to leukocytes (example: neutrophils via com-plement receptors, monocytes via a5b1), which will respond to the inflamed region, the spa-tial location of the ischaemic risk area can be identified with great sensitivity [Figure 2], [9]. It is important to note, how-ever, that molecular imaging of inflammation with ultrasound has also been achieved via the targeting of microbubbles

to cell receptors [examples: P-Selectin, intercellular adhe-sion molecule (ICAM-1), vas-cular cell adhesion molecule (VCAM-1)] on the surface of inflamed endothelial cells [2, 3]. Regardless, in the future, ultrasonic molecular imaging may offer clinicians the ability, in real time, to detect inflamed tissue during the active phase of leukocyte recruitment.

AtherosclerosisMolecular imaging with ultra-sound also offers the possibil-ity to detect atherosclerosis, the chronic inflammatory disorder that is one of the most important contributors to cardiovascular disease, and often progresses for decades before the onset of symptoms [2]. Inflammation in atherosclerosis involves plaque initiation and progression and is characterised by inflamma-tory tissues. Using ultrasonic molecular imaging to assess the extent of vascular inflamma-tion could potentially provide powerful information for early stages of disease as well as pre-dict future risks. ICAM-1 and VCAM-1, which are cell recep-tors expressed on the surface of endothelial cells, contribute to leukocyte adhesion during inflammation and play a criti-cal role in the progression of atherosclerosis [2]. Ultrasonic molecular imaging has shown that microbubbles targeted to ICAM-1 and VCAM-1 can help localise inflammatory tissue related to atherosclerosis. Moreo-ver, imaging of newly formed vas-culature sprouting from the vasa vasorum using ultrasonic molec-ular imaging of angiogenesis (microbubbles targeted to avb3) has recently gained traction as a potential way to predict plaque rupture [2, 8].

Acute cardiac rejectionOne of the leading causes of mortality in patients undergo-ing heart transplant is acute cardiac rejection. Currently, the “gold standard” for transplant rejection diagnosis is endomyo-cardial biopsy, which is a repeti-tively invasive procedure that

may span the course of the life of the patients [10]. Therefore, the development of a sensitive and noninvasive method for deter-mining failure of organ trans-plant is of critical importance. It is proposed that ultrasonic molecular imaging can help identify acute cardiac transplant rejection by targeting inflamma-tory tissue, specifically the over-expression of ICAM-1 on the surface of endothelial cells. It has been shown from in vitro experi-ments that microbubbles tar-geted to ICAM-1 will selectively adhere to rejecting tissue versus non-rejecting myocardium [2, 3, 10]. Therefore, in the future, ultrasonic molecular imaging may offer clinicians the ability

to effectively and noninvasively detect acute cardiac rejection.

Ischaemic memoryIt has also been proposed that molecular imaging with ultra-sound could aid in the analysis of recent myocardial ischaemic events (ischaemic memory) [2, 3, 6]. Currently, diagnosing acute coronary syndrome in the absence of ECG abnormalities can be challenging. Patients expe-riencing chest pains are often sent home prematurely from emer-gency departments due to misdi-agnosis (2 to 7%) [6]. Up to 26% of these high-risk patients may experience fatal complications [6]. Acute myocardial ischaemia and subsequent reperfusion is

Figure 2. Molecular imaging with ultrasound data for microbubbles targeted to three different molecular biomarkers. Each panel includes the

quantification of signal enhancement from targeted microbubbles, an over-lay of bound bubbles on traditional brightness mode ultrasound imaging, and immunohistochemical images at various time points in the study. Panel A: Microbubbles targeted to activated leukocytes (neutrophils) via comple-ment receptors. Panel B: Microbubbles targeted to leukocytes (monocytes) via 51 surface cell receptor. Panel C: Microbubbles targeted to vascular cell adhesion molecule (VCAM-1) biomarkers expressed on the endothelial

cell surface. Reproduced with permission from Behm et al [9].

18 MoLECULAr iMAGiNG

associated with the upregulation of leuko-cyte adhesion molecules (P-selectin) on the surface of endothelial cells, which persist even after ischaemia has been resolved. By targeting acoustically active microbubbles to P-selectin, it is possible to detect the inflam-matory tissue and obtain useful information about recent myocardial ischemic events. By detecting molecular markers that persist for hours after ischaemia, ultrasonic molecular imaging may provide a novel bedside detec-tion scheme for the diagnosis of acute coro-nary syndrome [2, 3].

Other applications of molecular imagingOther promising targets for ultrasonic molecular imaging include angiogenesis and thrombus imaging [2, 7]. Angiogenesis and arteriogenesis relate to the physiological process concerning the growth of new blood vessels and are critically involved in cardio-vascular disease as well as cancer growth [2]. During this process, endothelial markers such as VEGF-2, avb3 and VCAM-1, provide suitable targets for molecularly targeted con-trast agents. It has been shown that imaging of endothelial receptor of angiogenesis can provide information on vascular remodel-ling or response to therapy before blood flow changes occur [2]. This type of information can help elucidate plaque neovascularisation, chronic ischaemic heart and limb disease as well as cancer therapy response and tumour growth characteristics.

Targeting thrombus, which is the aggrega-tion of platelets forming a blood clot, is also possible with ultrasonic molecular imaging. This is accomplished by designing contrast agents to target platelets or fibrin using anti-bodies against glycoprotein IIb/IIIa recep-tor or RGD oligopeptides [2, 7]. It has been shown that this technique can enhance the surface of newly formed thrombi in vivo using animal models with carotid artery stenosis, thus providing an early detection strategy against thrombus [2].

Future directionsMolecular imaging with ultrasound is an exciting new field that, by the use of inexpen-sive and portable ultrasound systems with-out ionising radiation, offers the potential to detect pathology before phenotypic changes occur. Although significant advances have been made, the technologies enabling molec-ular imaging are still in development. Com-mercial imaging systems are still being opti-mised for molecular imaging, and targeted contrast agents for clinical and veterinary use are still not widely available. Although molecularly-targeted contrast agents have

been used in animal studies for nearly two decades, the safety and clinical utility of ultra-sound molecular imaging has only recently begun to be evaluated in humans. However, considering the potential advantages of this technique, it is reasonable to expect that ultrasonic molecular imaging may have a key role in the clinic in the future.

References1. Gessner R, Dayton PA. Advances in molecular

imaging with ultrasound. Mol Imaging 2010; 9: 117-27.

2. Lindner JR. Molecular imaging of cardiovascular disease with contrast-enhanced ultrasonography. Nat Rev Cardiol 2009; 6: 475-81.

3. Villanueva FS, Wagner WR. Ultrasound molecular imaging of cardiovascular disease. Nature clinical practice Cardiovascular medicine 2008; 5 Suppl 2: S26-32.

4. Ferrara KW, Borden MA, Zhang H. Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery. Acc Chem Res 2009; 42: 881-92.

5. Dayton PA, Rychak JJ. Molecular ultrasound imaging using microbubble contrast agents. Front Biosci 2007; 12: 5124-42.

6. Villanueva FS, Lu E, Bowry S et al. Myocar-dial ischemic memory imaging with molecular echocardiography. Circulation 2007; 115: 345-52.

7. Alonso A, Della Martina A, Stroick M et al. Molec-ular imaging of human thrombus with novel abciximab immunobubbles and ultrasound. Stroke 2007; 38: 1508-14.

8. Ten Kate GL, Sijbrands EJG, Valkema R et al. Molecular imaging of inflammation and intra-plaque vasa vasorum: A step forward to identifi-cation of vulnerable plaques? Journal of nuclear cardiology: official publication of the American Society of Nuclear Cardiology 2010; 17: 897-912.

9. Behm CZ, Kaufmann BA, Carr C et al. Molecu-lar imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation 2008; 117: 2902-11.

10. Weller GER, Lu E, Csikari MM et al. Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhe-sion molecule-1. Circulation 2003; 108: 218-24.

The authorsJason E. Streeter and Paul A. Dayton*Joint Department of Biomedical Engineer-ing University of North Carolina - North Carolina State University, USA*Corresponding author: Paul A. Dayton304 Taylor Hall, 109 Mason Farm Road, Chapel Hill, NC 27599-6136, USATel. +1 (919) 843-9521Fax +1 (919) 843-9520e-mail: [email protected]


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Hypoxia imaging in oncologyNon-invasive imaging techniques for the visualisation of physiological processes are gaining more and more interest in clinical oncology, with positron emission tomog-raphy (PET) techniques playing an impor-tant role in this field. In addition to the well known glucose metabolism tracer [18F]-fluorodeoxyglucose (FDG), other tracers have been synthesised for visualisation of different metabolic pathways. In oncology, one of the most important additional pieces of information besides energy turnover is tumour hypoxia, since it has been shown that hypoxic tumours have a worse prog-nosis and an increased resistance to radio-therapy. Several new tracers, for example [18F]-fluoromisonidazole (FMISO), have been developed and assessed for use in the evaluation of hypoxia [1, 2]. Clinical

research studies have been carried out to evaluate the prognostic potential of FMISO measurements [3] and for treat-ment adjustment tests [4]. The acquisition of in vivo FMISO PET data before the start of therapy allows the oncologist to get a more detailed view of the initial tumour microenvironment, and when the tech-nique is applied during therapy, it allows the effects and progress of the therapy to be monitored [5].

Nevertheless there are challenges to be overcome before FMISO PET can be intro-duced into clinical routine. Unfortunately, FMISO PET images provide a much lower contrast between the target and back-ground compared to FDG PET images [Figure 1]. This complicates data analysis and increases the potential effect of the observer on the interpretation. Several methods of improving FMISO PET image quality are being considered. This article highlights a way to improve image qual-ity by adjustment of the imaging protocol, without increasing the risk to the patient or generating costs for the hospital.

Principle of FMISO PET imagingThere are two main approaches for PET image acquisition. The first is dynamic 4D-PET image acquisition immediately after tracer injection. Using this method, the tracer uptake can be observed in detail at high temporal resolution, but image analysis is very complex. The second approach is static 3D-PET imaging after a defined waiting time. The trend in FMISO PET imaging is to use the second approach, because the principle behind PET imaging

using FMISO can be considered as the converse of that used in standard imaging technique using FDG PET in which the FDG accumulation is measured. In contrast FMISO accumulates in hypoxic regions but it is washed out of normoxic tissues so it is not tracer accumulation, but rather the washout effects that are of major interest in FMISO PET measurements. In addition these effects are more easily observed after the tracer is distributed throughout the whole body. While static FDG PET images are usually acquired about one hour post injection (p.i.), static FMISO-PET is car-ried more than two hours p.i., — in our opinion 4 hours p.i. is preferable [6]. Another distinctive difference between FMISO and FDG PET is image contrast. Unfortunately the contrast between the presumptive hypoxic region and the sur-rounding tissue is comparatively low in FMISO PET; this lower signal-to-noise ratio interferes with FMISO image analy-sis. There is thus a real need for new image analysis tools that would allow the han-dling of image data with low contrast, high noise, inhomogeneity and non-spherical target volumes [7]. The relatively poor reproducibility of FMISO measurements is also discussed in this article [8]. Each of these aspects requires intensive effort in order to improve imaging technology and image processing; every enhancement of image quality or reproducibility is a welcome development.

Improving PET image qualityImprovements in PET image quality, espe-cially noise reduction, could in theory be achieved through simple adjustments to the imaging protocols. One (clinically imprac-tical) way to do this is simply to prolong acquisition time since, technically, the signal-to-noise ratio increases with the duration of data acquisition. However, the requirement for a patient to keep still for a longer period of time is very difficult to achieve, and any eventual patient movement can nullify any improvement in image quality. Additionally, a long acquisition time leads to a decreased throughput of the number of patients being examined per day.

Another way to improve image quality is to increase the amount of tracer injected. Although this would indeed improve image

optimised imaging protocols for enhanced contrast in FMiso PEtthe technique of 18F Fluoromisonidazole positron emission tomography (FMiso PEt) has been shown to be able to image and quantitate hypoxia, which is one of the most important prognostic factors in several cancers. However, compared to FdG PEt images, images FMiso PEt have a much lower contrast between the target and background, so improvements in image quality, especially in noise reduction, would be of great benefit. such improvements can be achieved using simple adjustments to the imag-ing protocols. this article describes a way of improving image quality by adjusting the image protocol, without increasing the risk to the patient or generating costs for the hospital.

by dr r Haase and Prof. N Abolmaali


Figure 1. Visual comparison of sagittal slices of a) FDG PET and b) FMISO PET from the same patient.

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quality, the higher dose to which the patient would be exposed is not acceptable. When using FMISO, the tracer also accumulates in normoxic tissue, so a higher tracer vol-ume might not lead to an increased con-trast between target and background. The resurgence of time-of-flight (TOF) reconstruction techniques is a better approach for improving PET image quality without changing imaging protocols, but this method requires high precision detec-tors resulting in higher scanner costs.

Early on, it was demonstrated that static magnetic fields of about 4.5 Tesla were capable of reducing the high energy posi-tron range resulting in improved spatial resolution [9]. However, especially for [18F]-fluorine, this effect is negligible due to the already short mean range of about 0.3 mm. One biological feature that is sometimes overlooked is the observation of FMISO tracer washout with time. Based on this, PET data sets can be acquired at different time points after tracer injection to evalu-ate the influence of washout in hypoxic and normoxic tissues. If the washout tracer in tissues is significantly different, this effect could be used to enhance the ratio of activ-ity between the target volume and the surrounding tissue.

Optimised waiting time post injectionOur investigation on the influence of wait-ing time post injection was carried out by analysing FMISO PET patient data sets [6]. A group of patients was selected for an ongoing prospective study on head and neck squamous cell carcinomas (HNSCC). Data sets were analysed from 23 patients of median age of 55 years in clinical stages III (n = 9) and IV (n = 14) . The patients were imaged twice before combined

radiochemotherapy (RCT) and twice during RCT. After injection of 256±37 MBq tracer image acquisition was taken at 126±11 minutes p.i. (data set known as MISO2) and 241±16 minutes p.i. (data set known as MISO4). In total, 61 pairs of data sets (MISO2 + MISO4) were further analysed. The analysis included measure-ment of the standard uptake value (SUV) in predefined volumes of interest (VOI) of the data sets. Mean and maximum SUV were measured for three volumes in each data set: tumour-VOI, defined using a cor-responding FDG-PET data set, contrast-VOI, a small ellipsoid around the activity hot spot in the tumour-VOI, and back-ground-VOI, a volume in the neck mus-culature delineated on a corresponding CT dataset. These measures of SUV were fur-ther processed to analyse changes of image contrast between corresponding MISO2 and MISO4 data sets. For objectivity and comparability the analysis was carried out using different definitions of image con-trast: tumour-to-muscle ratio (TMR) and contrast-to-noise ratio (CNR). We found that, no matter which contrast definition was chosen, the measured contrast in the data set always increased during the two hours between the acquisition of MISO2 and MISO4. A Wilcoxon-matched-pairs test of the data was performed and showed a statistically significant difference between corresponding MISO2 and MISO4 con-trast measurements. An example of a pair of data sets is shown in Figure 2 and dem-onstrates the effect on the image quality. Finally it must be noted that, since the half life of [18F]-fluorine is 110 minutes, the count rates at MISO4 were approximately halved compared to MISO2. Nevertheless, the reduced number of events measured was still high enough for further image analysis to be carried out.

We would therefore recommend using data sets acquired four hours p.i. when working with FMISO as a hypoxia tracer. The idea of increasing waiting time before measure-ments has also investigated by Dubois et al using the hypoxia tracer [18F]-EF3 in a rat model [10] Their conclusions were similar to ours, but they found that contrast values four hours p.i. were similar to the values for FMISO data sets two hours p.i.. Further development and conclusionsThe research on improvement in quality of FMISO-PET data should not only focus on improved image protocols. Imaging devices and reconstruction algorithms to improve spatial resolution are currently

being developed at our partner institution Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Germany. In addition it is impor-tant that observer-independent image anal-ysis tools for volume data with low contrast and high noise should be developed.

Even though the development of FMISO PET has now been going on for more than a decade, it has not yet become widely accepted in the clinic largely because of some outstanding challenges to be over-come, such as limited reproducibility and low image contrast. However even small improvements increase the qual-ity of images. The proposed improvement of image quality by extending the waiting time between the tracer injection and the PET scan may be challenging for patient scheduling in routine clinical practice, but is an excellent approach to enable further image analysis.

References1. Rasey JS et al. Int J Radiat Oncol Biol Phys 1996;

36(2): 417-28.2. Rajendran JG et al. Clin Cancer Res 2006;

12(18): 5435-41.3. Lee N et al. Int J Radiat Oncol Biol Phys 2009;

75(1): 101-8.4. Thorwarth D et al. Int J Radiat Oncol Biol Phys

2007; 68(1): 291-300.5. Eschmann SM et al. Radiother Oncol 2007;

83(3): 406-10.6. Abolmaali N et al. Nuklearmedizin 2010; 50(1).7. Lee JA. Radiother Oncol 2010; 96(3): 302-7.8. Nehmeh SA et al. Int J Radiat Oncol Biol Phys

2008; 70(1): 235-42.9. Wirrwar A et al. IEEE Transactions on Nuclear

Science 1997; 44(2): 184-189.10. Dubois L et al. Eur J Nucl Med Mol Imaging

2009; 36(2): 209-18.

The authorsRobert Haase1 andProf. Nasreddin Abolmaali 1, 2 (correspond-ing author)1 OncoRay - Imaging, National Centre for Radiation Research in Oncology, TU DresdenMedical Faculty and University Hospital Carl Gustav Carus, TU DresdenFetscherstraße 74, P.O. Box 4101307 Dresden, GermanyTel: +49 351 458 7414Fax: +49 351 449 210 394e-mail: [email protected] Institute and Policlinic for Diagnostic Radiology, Medical Faculty and University Hospital Carl Gustav Carus, TU DresdenFetscherstr. 74, P.O. Box 4501307 Dresden, Germany


Figure 2. An example of FMISO PET data sets acquired at different time points after injection.

The top row shows the sagittal plane of an oropharyngeal carcinoma, and the bottom row shows corresponding axial slices. The window-ing properties are identical for both data sets.

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The advent of 3D imaging for breast examination has opened a new era in mammography and breast cancer diagnosis. Unlike conventional mammog-raphy, which is based on a stationary tube and produces a 2D projected image, 3D systems use a moving X-ray source that swivels in a 50-degree arc over the breast to acquire multiple projection images. These individual slices of the breast are subsequently reconstructed into a 3D image. The 3D technology offers a number of advantages, such as improved detail recognition and easier localisation of micro-calcifications, while over-coming the limitations of conventional 2D mam-mography resulting from tissue overlapping that may hide lesions or cause benign areas to appear suspicious. The fact that there are fewer false posi-tives and fewer inconclusive images could also significantly reduce the number of biopsies.“Tomosynthesis will make mammography less stressful to both the physician and the patient. According to first impressions, additional examinations and interventions can be omit-ted in all good conscience. Lesions hiding in the gland tissue are detected earlier”, says Dr. Renate Tewaag of the Radprax group, a net-worked practice for radiology, nuclear medicine and radiation therapy in Wuppertal, and one of the first radiologists in Germany to have started working with the new technology.Hologic has been a pioneering company in this field, selling Tomosynthesis commercially in 40 countries for almost two years with hundreds of install sites in Europe, the Middle East, South

America, Canada, Mexico and Thailand, and several hundred more sites in the USA ready to switch to tomosynthesis now that the company has received final FDA approval for its Selenia Dimension 2D/3D mammography system – currently the only breast tomosynthesis product approved by the FDA for marketing in the USA.Siemens has quickly followed by expanding its Mammomat Inspiration system with a 3D tomosynthesis capability, while GE is expected to announce its latest developments in 3D breast imaging at the 2011 European Congress of Radi-ology (ECR) in Vienna.For the 40% of women with especially dense breast tissue (e.g. in small breasts), 3D tomosynthesis image generation uses an algorithm to remove superimposed dense gland tissue. Dense breast tissue also constitutes a particular indication for an additional ultrasound examination which is now greatly facilitated by automatic breast scan-ning (as provided by the Acuson S2000 ABVS). The next step will be fusing mammography with ultrasound images. While some ultrasound scan-ners (such as GE’s LOGIQ E9) are capable of fusing ultrasound with previously acquired CT, MR or PET images, the technology for creating a composite image generated by both mammogra-phy and ultrasound modalities is not yet on the market (although Siemens is actively currently working on it). It could provide physicians with a unique insight into the patient’s anatomy and set new standards of accuracy and sensitivity in breast cancer diagnosis.

Early identification of pre-eclampsia

Page 26 - 28

The success of a multidisciplinary breast and breast screeening

clinic

Page 30 - 31

Increased diagnostic accuracy in breast

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March/April 2011


Women’s health special

Women’s Health Special Looking at industry’s contribution to breast tomosynthesis and beyond

Trade fair and congress “Hospital Build” in Europe for the first timeThe trade fair and congress “Hospital Build” has already established its presence in Asia and the Middle East over the last two years. Held from 4–6 April 2011 in Nuremberg, Germany, the trade fair and congress will now offer European directors, CEOs and CFOs of hospitals, as well as sup-pliers and service providers in the areas of process, project and change management, business development, procurement and logistics, a new cross-border platform for exchange and discussion. The affiliated three-day congress featuring international speakers will, in a parallel series of confer-ences, focus on the topics of design, building and refurbishment of hospitals, as well as healthcare management, process optimisation, non-medical services and patient hotels. A “Leaders in health care” conference will also take place during the trade fair and congress. In this sub-conference international experts will discuss issues related to health care policy and man-agement. For instance, Frédéric Dubois from Médi-Partenaires, France’s largest operator of private clinics, will report on trends in restructuring and turnaround management in the French hospi-tal market. Eke Zijlstra from MC Atrium, one of the leading general hospitals in the Netherlands, will provide an insight into the Dutch hospital market. Prof. Dr Thomas Ittel, from the University Hospital Aachen, Germany will discuss the issues of factuality, transparency, efficiency through joint action, personal responsibility, quality and swiftness. Other managers from leading European hospitals will share practice-oriented insights within the Leadership conference.

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26 WoMEN’s HEALtH

It is now 45 years since the eminent gynaecologist Professor T. N. A. Jeffcoate described pre-eclampsia as a ‘disease of the-ories’. In his 1966 presidential address to the British Royal Society of Medicine, Jeffcoate urged obstetricians to be ‘extremely criti-cal’ in diagnosing pre-eclampsia: countless studies, he said, had failed to reveal a cause because the ‘laboratory worker, dependent on the obstetrician for his material, was often investigating a wide variety of dis-eases whilst under the impression that he was dealing with one’.

Today those warnings seem just as relevant as ever. Pre-eclampsia (PE) remains a clini-cal challenge, with its diagnosis still defined by non-specific markers, its severity imper-fectly stratified, and patient progression unpredictable. As a result, the evaluation of

women with suspected PE is resource- and time-intensive, with much effort wasted on attempts to diagnose accurately, stratify risk and ensure an appropriate level of care for those women who need it.Now, however, with the recognition of more specific parameters in the pathophysiology of PE and the availability of tests for their measurement, the diagnosis of PE and the accurate risk assessment of hypertension look set to move from an imprecise evalua-tion based on clinical symptoms and labo-ratory parameters, to an accurate scientific evaluation that achieves both diagnosis and risk assessment with high specificity. The Alere Triage PLGF (placental growth factor) assay [Figure 1] is a new biomarker test whose initial use will help confirm a diagnosis of early onset PE; it is now known that a low level of placental growth factor is diagnostic of PE in pregnant women with classical but non-specific signs of the con-dition. Moreover, in women who develop hypertension in pregnancy, a low level of placental growth factor indicates a high risk for a complication.

PE: a clinical syndromeAs Jeffcoate suggested, PE is a clinical syn-drome, not a single disease, whose principal features are raised blood pressure (usually defined as >140/90 mmHg) and an excess of serum proteins in the urine (>300 mg in a 24-hour collection). As with any syn-drome, the presence of one feature is not necessarily indicative of the other. Indeed, an NIH (National Institutes of Health) working group on high blood pressure in pregnancy reported in 2000 that, while

15-20% of pregnant women will become hypertensive, only a small proportion of them will actually develop PE [1].

Similarly, proteinuria is not always indica-tive of PE, nor even associated with hyper-tension. Thus at the point-of-care there is a clinical tendency for ‘over diagnosis’ and unnecessary monitoring, with decisions based on non-specific signs with arbitrary cut-off values. As the NIH working group reported: ‘Although our understanding of this syndrome has increased, the crite-ria used to identify the disorder remain a subject of confusion and controversy. This doubtless reflects the fact that pre-eclampsia is a syndrome, and that attempts at definition use arbitrarily selected markers rather than changes of pathophysiologic importance.’

This is not to say, however, that today’s precautionary approach is misdirected. PE is still associated with high rates of mor-bidity, both for the mother and the baby. A Lancet review from 2005 described the maternal syndrome as ‘probably more than one disease with major differences between near-term pre-eclampsia with-out demonstrable foetal involvement and pre-eclampsia that is associated with low birthweight and preterm delivery’ [2]. This two-stage manifestation of PE - maternal and foetal syndromes - and the factors which link them add further complexity to the diagnosis and increases the chal-lenge of explaining PE’s pathophysiology. Yet the bare facts remain that PE is one of

Pre-eclampsia: new biomarkers aid in early identificationPre-eclampsia (PE) is a clinical syndrome that affects 2-8% of pregnancies, and which is associated with high maternal and perinatal morbidity and mortality if it is not identified and managed. the condition typically occurs after 20 weeks gestation, and while clinical signs are hypertension and proteinuria, around 15-20% of pregnant women develop hypertension and many pregnant women develop proteinuria, but only a small proportion of them will develop PE. Measurement of biomarkers that are a direct reflec-tion of placental function can enable more effective diagnosis and manage-ment of PE. A highly sensitive and specific test for placental growth factor (PlGF) that can be carried out at the Point-of-Care is showing great promise for early diagnosis of the pre-35 weeks form of the PE syndrome.

by Brian Conibere


Figure 1. Alere Triage PLGF and Alere Triage MeterPro. Using the system, assays of PlGF can be carried out at the bedside or other Point-of-

Care situations.

WHAT IS PRE-ECLAMPSIA?* A clinical syndrome affecting 2-8% of

pregnancies- Pregnancy-specific multi-organ

syndrome- Typically occurs after 20 weeks gestation- Clinical signs are raised blood pressure

and proteinuria

* 15-20% of pregnant women develop high BP

- 20-25% of these develop pre-eclampsia (3-5%)

- Much higher rates in developing coun-tries; associated with high maternal and perinatal morbidity and mortality if not

identified

27

the most common complications of preg-nancy, affecting between 2 and 8% of all pregnancies, and causing a high propor-tion of premature deliveries, many of them as a result of treatment [3]. As many as 14% of all maternal deaths in the UK are attributed to PE. Similar data on PE-attrib-utable maternal deaths are found in other countries in Western Europe. Pre-existing hypertension, renal disease and diabetes are all associated with an increased relative risk of developing PE, making the diagno-sis even more difficult. Diagnosing PEEven in the absence of pre-existing hyper-tension, blood pressure measurements in the ambulatory setting of an antenatal clinic - where PE is often first suspected - will rarely be diagnostic or reliable. The cut-offs no doubt owe more to his-torical acceptability than specificity, and will inevitably lead to over diagnosis and misaligned risk stratification. Similarly, measurement of excreted protein can-not be reliably confirmed in a one-off ambulatory or even acute care setting; 24-hour (or an appropriately timed) urine collection is necessary.

Nevertheless, it is the outcome of these ini-tial assessments which defines the level of risk and the extent of future surveillance. Those patients perceived as high risk will require close monitoring as in-patients or with frequent clinic visits. Patients will be monitored for sharp increases in blood pressure, the presence of urinary proteins and evidence of foetal growth restriction. Such monitoring is easily carried out (even if from daily out-patient visits) but is lim-ited in its specificity. Thus, while new onset hypertension might be detected in 10% of antenatal tests, only around one in five of these cases will actually go on to have PE. Conversely, there may be some women who develop eclampsia who had no signs of hypertension or proteinuria, and who, by definition, would not be diagnosed as hav-ing PE using current methods. Similarly, women who develop HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet counts), another variant of PE, will also be outside the current diagnostic definition of PE.

Biomarkers to facilitate diagnosis of PENow, however, these serious and long-standing shortcomings in the diagnosis and risk assessment of PE look set to be bridged by the discovery of biomarkers specifically associated with the hitherto ill-defined

pathophysiology of PE. The recent avail-ability of clinically meaningful diagnostic tests to measure levels of these biomark-ers now allows the accurate identification of women with ‘true’ PE, rather than just identifying women with hypertension and proteinuria. The latest biomarkers are a direct reflection of placental function and, while having a clear application for facili-tating the diagnosis of PE, will probably also have a further role in patients with hypertension that typically precedes PE.

Placental Growth Factor (PlGF)The biomarker which appears to be most promising is placental growth factor (PlGF), a molecule that is essential for angiogenesis, whose concentrations in pregnancy are dependent on the placenta; studies have consistently shown that serum levels of PlGF in both early and late onset PE are lower than in healthy pregnancies.

From around nine weeks into a normal pregnancy the uterine spiral arteries are transformed from thick-walled, muscular vessels into more flaccid tubes to accommo-date the increased uterine blood flow that the pregnancy requires. However, in the case of poor placental development as seen in PE, these uterine arteries remain tightly coiled, thereby restricting placental blood

flow [Figure 2]. Accompanying this is an angiogenic imbalance (both pro- and anti-angiogenic factors) which can be quantified by measuring circulating biomarkers, and in particular PlGF. Levine et al showed that in a normal pregnancy PlGF levels begin to rise at around ten weeks, from around 100 pg/mL to 900 pg/mL at 29-32 week. Thereaf-ter levels declining until delivery. However, in PE this rise and fall is considerably lower throughout the pregnancy, and even at 13 weeks it was found to be lower in women destined to develop PE (mean 90 pg/mL vs. 142 pg/mL) [5].

The PELICAN-1 study showed that the Triage PLGF test had a 95% sensitivity and 95% specificity for the differentiation of women with early onset PE from women with a normal pregnancy outcome, and identified 95% of women with and with-out PE at less than 35 weeks gestation [6]. In fact, the two women with ‘PE’ missed by the Triage PLGF test went on to have normal uneventful pregnancies and were probably not affected by the condition.

An accurate diagnosis at such an early stage of pregnancy suggests that it is critical (as it is at any time) that management plans are made and triage begun. Of course any treatment during pregnancy, and the ulti-mate timing of delivery, are central to the obstetric outcome. Thus, suspicious signs in early pregnancy that are confirmed as PE with PlGF testing can now alert the physician to a very high likelihood of PE.

Additional biomarkersPlGF is not the only biomarker in PE. While PlGF is pro-angiogenic, and thus


Figure 2. Restricted placental blood flow seen in pre-eclampsia.

WHERE PLGF LEvELS MAy BE LOW

Patients may test positive in* PE and atypical PE

(eg, non-hypertensive)* Placental insufficiency

* Foetal growth restriction* HELLP syndrome

28 WoMEN’s HEALtH

reflects blood vessel growth (circulating at high levels in a normal pregnancy), the majority of PlGF in PE binds to an anti-angiogenic inhibitory receptor, namely fms-like tyrosine kinase (sFlt-1). Levels of the latter — as well as the sFlt-1:PlGF ratio — have also been shown to reflect the risk of PE. Studies, however, have shown that ‘two-marker’ measurement is unnecessary, and does not add further diagnostic information over and above a second-generation PlGF immunoassay such as Triage PLGF. Benton et al showed in a study of 132 blood samples (45 cases of PE and 87 matched controls) that the Triage PLGF assay had a clinical sensitiv-ity of 100% [7].

The bottom line in the clinic is that women with low PlGF levels, and not hyperten-sion alone, detected before 35 weeks ges-tation will require close management. Indeed, pregnancies with low PlGF levels will require treatment (delivery) as soon as possible after testing; however, pregnancies with PlGF levels within a normal range are likely to progress longer, often to full term.

Of course, PlGF alone does not provide all the answers, and it is not expected to do more than identify placental dysfunc-tion as a cause of PE or hypertension in pregnancy. As with any new biomarker, pregnancies will continue to be assessed using the currently available laboratory parameters until clinicians are confident about using PlGF. At present, the Triage PLGF test is intended for use in suspected PE before 35 weeks gestation, because late onset PE can be caused by maternal as well as placental factors. However knowing

which of these earlier pregnancies require early intervention will allow clinics to allo-cate resources more effectively. Tests using Triage PLGF can also be conducted simply and reliably at the point-of-care on the benchtop Alere Triage MeterPro analyser, while the sFlt-1:PlGF assay is designed for laboratory measurement.

Evidence suggests that the measurement of PlGF levels will also indicate cases of atypical PE, in which there are some signs and symptoms of PE but not the usual hypertension or proteinuria. Thus, atypi-cal PE might be considered in cases of ges-tational hypertension without proteinuria but with at least one of the symptoms of PE, namely haemolysis, thrombocytope-nia, and elevated liver enzymes. A similar diagnosis might be suspected in cases of gestational proteinuria without hyperten-sion but with these same symptoms. Many of these cases will progress to PE (even if atypical) and in many the unchecked pro-gression will result in preterm delivery and/or foetal growth restriction [8]. Such women will require close observation for the early detection of PE, including fre-quent prenatal visits and serial evalua-tion of platelets and liver enzymes, and/or foetal growth (serial ultrasound), as will women with the suspect symptoms of HELLP syndrome.

Commenting on the importance of an accurate diagnosis of PE, Christopher Redman, Emeritus Professor of Obstet-rics at Oxford, has said: ‘No complication of human pregnancy is both so common and so dangerous for both mother and baby as pre-eclampsia. Yet its detection

is fraught with uncertainties leading to over-management for many expectant mothers while others have serious prob-lems that go undetected. A reliable diag-nostic blood test, such as the Alere Triage PLGF, which potentially can be used close to the mother without the need for elabo-rate equipment or trained laboratory staff, is a major step forward for both pregnant women and those who look after them.’

That ‘step forward’ may now, after so many years, raise the diagnosis of PE from Jeffcoate’s ‘disease of theories’ to a more sci-entific and evidence-based level. Through-out the last 45 years there has been a clear need to redefine PE, and PlGF is likely to play a significant role in that new definition. With the opportunity to measure PlGF with accuracy and reliability, it will be possible to develop appropriate clinical pathways spe-cific to PE and its sub-types, and this should lead to improved standards of care, better allocation of health resources and lower costs. For the patient, there are likely to be fewer missed cases and fewer unnecessary deliveries before full term.

References1. Roberts JM, Pearson G, Cutler J, Lindheimer

M. Summary of the NHLBI Working Group on Research on Hypertension During Preg-nancy. Hyptertension 2003; 41: 437-445.

2. Sibai B, Dekker G, Kupferminic M. Pre-eclampsia. Lancet 2005; 365: 785-799.

3. Khan KS, Wojdyla D, Say L et al. WHO analy-sis of causes of maternal death: a systematic review. Lancet 2006; 367: 1066–74.

4. Steegers EAP, Von Dadelszen P, Duvekot JD, Pijnenborg R. Pre-eclampsia. Lancet 2010;DOI:10.1016/S0140-6736(10)60279-6

5. Levine RJ, Maynard SE, Qian C et al. Circulat-ing angiogenic factors and the risk of preec-lampsia. N Eng J Med 2004; 12: 672-683.

6. Knudsen AB et al. A single rapid point-of-care placental growth factor determination as an aid in the diagnosis of pre-eclampsia. Submitted for publication.

7. Benton SJ et al. Placental growth factor (PLGF) as a diagnostic test for pre-eclampsia: a per-formance comparison of two commercial immunoassays. Submitted for publication.

8. Sibai BM, Stella CL. Diagnosis and manage-ment of atypical preeclampsia-eclampsia. Am J Obstet Gynecol 2009; 200: 481 e1-7.

The authorBrian ConibereGlobal Product ManagerAlere Internationale-mail: [email protected] www.alere.com www.ihe-online.com & search 45787


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twelve-crystal transducer technology was initially intro-duced in 2007 for foetal mon-itoring. since then the tech-nology has been extensively tested and it has been proven that the 12-crystal waterproof ultrasound transducer attains a wider beam area for a more homogenous signal at greater depths, thus provid-ing increased sensitivity and higher clinical confidence.

the 12-crystal ultrasound sen-sor provides a wider beam area than conventional trans-ducers.as has been shown by a comparative analysis of the sound field distribution of 12-crystal and 8-crystal ultra-sound transducers at differ-ent depths of 6 cm, 9 cm and 12 cm. it was found that the beam area became larger as the depth increased, and that the beam area of the 12-crys-tal transducer was wider than that of the 8-crystal trans-ducer at the same depth, this ensures that the foetal heart was within the ultrasound beam despite foetal or mater-nal movement [Figure 1].

the coverage provided by the 12-crystal probe is more homogenous. thus, the sound field distribution of the 12-crys-tal transducer appears round and homogenous, while that of the 8-crystal transducer appears rectangular and

diffuse as the depth increases [Figure 1]. the more homog-enous the signal, the greater its accuracy and capabil-ity of providing a reliable signal, thus reducing the number of times the 12-crys-tal transducer must be reposi-tioned for patients of different sizes and at different stages of gestation.

in addition to its ability to offer a more homogenous coverage and a larger focal area than other conventional transduc-ers, the 12-crystal probe offers advanced performance, reli-ability and ease of use. the 12-crystal transducer’s larger focal area and homogenous distribution, and the resultant increased sensitivity, allow signals to be detected with

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30 WoMEN’s HEALtH

Dr Fabienne Liebens is gynaecologist-oncologist and coordinator of the Multidis-ciplinary Breast Clinic and Breast Screen-ing Clinic ISALA, part of CHU Saint-Pierre hospital in Brussels, Belgium. She is pas-sionately involved in saving women’s lives and assumes her societal responsibilities as vice-president of the Belgian section of Europa Donna, the independent European Breast Cancer Coalition that currently has 42 member countries. The coalition works to raise awareness of breast cancer and mobilise the support of European women in pressing for improved breast cancer education, appropriate screening, optimal treatment and care as well as increased funding for research.

A Breast Clinic with a heart for womenWith some 170 cases per year, the Multi-disciplinary Breast Clinic and Breast Screening Clinic ISALA is one of Belgium’s

largest breast centres and a key referral clinic in the country. “Yearly we consult 6,000 women and perform some 13,000 breast examinations”, explains Dr Fabienne Liebens. “Our staff numbers 40, of whom 80% are women including eight radiolo-gists and seven breast clinicians. We also consult with gynaecologists, surgeons and GPs, and work with an oncology service in our building.”

The Breast Clinic was started in 1991 within the Saint-Pierre Hospital campus and moved into its own facilities close to the hospital in 2007. The facilities are astounding because of their look and feel, which is completely different from the classical hospital design. “We didn’t want women to feel as if they were coming to a hospital”, underscores Dr Liebens. “The reception and waiting room area is more like a lounge, which allows women to wait for their consultation in a relaxed way.

The interior was designed by a female decorator who is also a patient, so she knows the clinic. People see no evidence of mammography equipment or technol-ogy at the standalone clinic. All imaging, interventions and surgical procedures take place back at CHU Saint-Pierre.”

The clinic’s décor helps in gaining the loy-alty of women who enter the screening programme, believes Dr. Liebens, but it is

no doubt the complete holistic focus that is the most reassuring and comforting. “Our motto is: behind each breast we treat, there’s also a woman to heal”, says Dr Liebens.

Clinic’s staff reflect multicultural dimensionSince the clinic is part of a public hospi-tal, all patients receive the same treatment regardless of ethnic background. About two thirds of patients are ethnic Belgians. The clinic’s recruitment is based on breast cancer prevention programmes. Screening

trivialising breast cancer kills women“As we become more successful in the early detection and treatment of breast cancer, we tend to trivialise it. yet one out of nine women still get breast cancer. Half of them become depressed, their partners don’t know how to react and their families are in disarray. We need to stop trivialising breast cancer. it kills women”, says dr Fabienne Liebens, Head of the saint-Pierre Hospital’s Breast Clinic, Brussels, Belgium and one of the world’s leading experts on breast cancer and mammography.


Closing in on DR image quality

Radiologist Dr Martine Van Beveren leads a team of seven mammography radiologists who interpret images using two Agfa HealthCare CR systems. They examine 45 women daily for clinical purposes, proactive screening or medical follow-up resulting in around 13,000 studies annually.

“As a mammography radiologist, I am particularly concerned about breast image quality and dose reduction. To make the patient as comfortable as possible, I also prefer fast solutions, which significantly reduce waiting and examination times. Agfa HealthCare’s DX-M Digital Mammography system, in combi-nation with CR HM5.0 needle-based Mammo detectors, con-siderably improves the performance of existing CR solutions. Our tests show that image quality using this approach is very close to full Direct Radiography (DR) image quality, but with a considerable dose reduction.”

“I appreciate Agfa HealthCare’s commitment to mammogra-phy. The company seeks solutions that provide the best care for patients. I particularly like the low dose for patient safety, easy to manipulate tools for examination speed, and personalised

profiles for radiologist efficiency. Generally speaking, in the future, I think radiology will see further enhancements in areas such as lower doses and better contrast for dense breasts.”

Dr. Martine Van Beveren sees a considerable dose reduction with the DX-M CR solution.

“Our motto is: behind each breast we treat, there’s also a woman to heal.”

31

is voluntary in Belgium, with only one woman out of two entering a programme. This explains the relatively high number of ethnic Belgian patients compared to the more multicultural patient popula-tion of CHU Saint-Pierre. Dr Liebens says “Regardless, we integrate the multicultural aspect into our staff: we have Belgians that are French-, Dutch- and English-speaking. We also have staff from Greece, Poland, Morocco, Chile, Iran and Vietnam. This allows us to cover most of the languages needed by patients. CHU Saint-Pierre‘s multicultural section provides interpreters, but we don’t often need them.”

The clinic has two sites where it is active and there-fore requires strong quality control. Dr Liebens is keenly focused on quality in treat-ing a patient. The breast nurse is key to this concept. She’s the patient’s personal guide throughout the complete proc-ess. She is also the person to liaise immediately with medi-cal and clinical staff on behalf of the patient, and is present at all medical consultations. “We have one breast nurse, supported by four assistants, who interact with other clini-cal disciplines,” Dr. Liebens says. “The governmental plan stipulates one breast nurse for every 150 cases”.

Patients appreciate holis-tic guidance“From a study of 1,000 patients leaving the surgical oncology department, 92% are satis-fied with their care,” she adds. “Key to this satisfaction is that psychological support is not an option; rather it is a fully integrated component of all treatment. Few if any patients refuse this, and we found that even six months after the surgi-cal procedure, 65% considered the psychological support and counselling to have been very useful. This proves the impor-tance of our holistic view of the patient.”

Dr Liebens continues: “The clinic’s technological support of digital mammography sys-tems, image enhancement software and associated prod-ucts is ‘well hidden’, but it is of course key to our success. We need fast and productive solu-tions and immediate support in case of problems.”

“Agfa HealthCare is commit-ted to the fight against breast cancer. The company provides reliable technology, but is also a partner with us in providing patient-focused programmes through support of a wide range of initiatives to increase breast health awareness among women and medical profes-sionals alike. Agfa HealthCare was a key supporter of our

release of Marie Mandy’s book, ‘Through the eyes of an Ama-zon’. This remarkable publica-tion conveyed, through both words and art, the real-life experiences of Marie, a breast cancer survivor. The book will give heart to women who must face this disease, its social and emotional ramifications, and treatment up to and including partial or radical mastectomy.”

Encouraging society to support breast cancer prevention researchDr Liebens is highly concerned about the lack of focus on pri-mary prevention efforts involv-ing breast cancer. The incidence of this disease in developed countries is increasing, but there’s little focus by institu-tions and industry on primary prevention. “The knowledge women have on how to prevent breast cancer is astonishingly little. The first Belgian research on this issue was, surprisingly, done only last year. It showed that 85% of women questioned

have no knowledge whatsoever of risk factors for breast can-cer.” Video displays in the clin-ic’s lounge provide preventive information, and displays in a separate area convey results of prevention studies.

The situation is even more worrying for breast cancer preventive research, feels Dr. Liebens. “In Belgium, where breast cancer incidence is 33% higher than the European average, there’s just one study currently underway in pri-mary prevention for women after menopause, while there are hundreds of studies on therapeutic products. To meet my concerns, I have developed a risk calculator based on the Tyrer-Cuzick International Breast Cancer Intervention Study Model for Breast Cancer Risk Prediction. It allows us to predict the breast cancer risk of an individual woman and determine whether pharmaco-logical preventive treatment is appropriate in her case.”


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The reception and waiting room area of the breast clinic is more like a lounge, which allows women to wait for their consultation in a relaxed way.

32 WoMEN’s HEALtH

Breast cancer is the most frequently diag-nosed cancer and the leading cause of can-cer death in females worldwide, accounting for 23% (1.38 million) of the total new can-cer cases and 14% (458,400) of total cancer deaths in 2008 which is the latest year for which data have been collected [1]. In gen-eral, incidence rates are high in Western and Northern Europe, Australia/New Zealand and North America; intermediate in South America, the Caribbean, and Northern Africa; and low in sub-Saharan Africa and Asia. The factors that contribute to the international variation in incidence rates largely stem from differences in reproductive and hormonal factors and the availability of early detection services. Reproductive factors that increase risk include a long menstrual history, recent use of postmenopausal hormone therapy or oral contraceptives, and nulliparity or late age at first birth. The increases in the incidence of breast cancer that have been observed in many Western countries in the late 1980s and

1990s are most likely the result of changes in reproductive factors (including the increased use of postmenopausal hormone therapy) as well as an increased screening intensity [1]. Incidence rates in some countries, including the United States, United Kingdom, France and Australia, sharply decreased from the beginning of the millennium, partly due to lower use of combined postmenopausal hormone therapy. Breast cancer death rates have been decreasing in North America and several European countries over the past 25 years, largely as a result of early detec-tion through mammography and improved treatment [1].

MammographyDiagnostic mammography has been shown to have an average sensitivity for the detec-tion of cancer of 75%, and 60% to 80% of all subsequent biopsies are negative for cancer [2]. In some cases magnetic reso-nance imaging (MRI) can contribute to

solving such problems and has been shown to increase sensitivity to about 95%, but with a specificity that is lower than that of mammography [3]. For these reasons, it is desirable to have a different approach to breast imaging, such as the use of addi-tional techniques that could act as adjuncts to mammography. One such technique that is showing considerable promise is that of computed tomography using near infra-red laser (CTLM) of the breast.

Computed Tomography Laser MammographyCTLM is based on the detection of neovas-cularisation and the angiogenesis that is asso-ciated with the growth of tumour cells. It has been shown that tumours are unable to grow larger than approximately 1 mm3 without developing a new, hypoxia-triggered blood supply [4], [Figure 1]. A CTLM instrument has been developed to detect such angiogen-esis. The system uses a laser of wavelength 808nm in the NIR region of the spectrum

increased diagnostic accuracy in breast screeningBreast imaging is considered to be the primary medical procedure for the evaluation of women for signs suggesting breast cancer. While mammog-raphy screening has been credited with saving lives, the modality may miss as many as 10% to 15 % of breast cancers. Multimodality breast cancer detection technologies are being applied to improve detection methods, to compensate for inherent reader variation errors and to find safer methods for screening younger women and those with dense breasts. despite such efforts, current modalities have yet to show improvement in outcomes. in addition, negative biopsy rates can be as high as 60 - 80 % showing that many women are being subjected to unnecessary and traumatic pro-cedures. All this points to the need for adjunctive breast cancer detection technologies. this article describes the promise of the computed tomogra-phy laser mammography (CtLM) technique, which uses non-ionising laser radiation to detect angiogenesis associated with tumours in the breast.


Figure 1. The angiogenesis process. Images created for National Cancer Institute.

Figure 2. Absorption of light (vertical axis) in hae-moglobin, water and fat at various wavelengths (horizontal axis). CTLM uses a wavelength of

808nm, the point at which both oxy- and deoxy- haemoglobin absorb the near infra red light but

water and fat absorb virtually none.

Figure 3. Correlation between mammography, CTLM and magentic resonance imaging in a 28-year old woman with an invasive ductal carcinoma and cutal carcinoma in situ (high grade) in her left breast.

33

that matches the crossover point of absorp-tion of both oxygenated and deoxygenated haemoglobin [Figure 2]. The laser in the CTLM device is tuned specifically to this intersection to produce images showing an attenuation absorption difference between haemoglobin and water or fat molecules. This principle enables the CTLM device to produce a 3D image of the haemoglobin distribution in the breast while tissues rich in fat and water appear transparent. At the particular wavelength chosen, blood absorbs most of the light, providing excellent 3D and tomographic images of the entire breast from the chest wall to the nipple.

There are several theoretical advantages to such optical methods based on near-infra red imaging of the breast [2]. First, the breast is fully accessible for imaging with optical methods because of its surface location, rel-atively small size and absence of bone struc-tures. Secondly, at 800 nm it is possible to exploit the difference in absorption between total haemoglobin and water or fat as an intrinsic contrast. Haemoglobin thus acts as a natural contrast medium and computed laser tomography produces a “haemoglobin angiogram” that reveals the normal vascular structures of the breast [Figure 3]. Because all tumours require neoangiogensis to sur-vive and grow, NIR tomographic imaging can detect tumours within the breast. Other advantages of the technique are that no ion-ising radiation is needed and that it is rela-tively inexpensive and easy to use. A com-mercially available CTLM system has been produced by Imaging Diagnostic Systems Inc, Plantation, FL, USA and been evaluated in several cohorts of patients with breast cancer. The system is approved for sale in all international markets.

Clinical evaluation of CTLM A study of 82 patients, of whom 79 had unclear lesions on mammography, ultra-sound or MRI, or had palpable masses on physical examination, were studied using

CTLM [2]. Seventy-nine patients were biop-sied after their NIR scans were performed. The results of this study showed that the combination of the commercially available continuous-wave NIR laser mammographic system, (CTLM) plus mammography was more accurate than mammography alone, with a statistically significant increase in the area under the curve (AUC) for mammogra-phy plus CTLM compared with mammog-raphy alone [2]. Of particular interest was the observed correlation between CTLM, not only with mammography but also with MRI [Figure 3]. Although this preliminary study was limited by several factors includ-ing the relatively small numbers of patients studied, the results were promising enough to justify further investigation.

Women with dense breasts It is well-known that mammography has low accuracy in women with dense breasts, who constitute 40% of the at-risk population. A study involving 155 women (23 - 74 years of age, median 41 years of age) was carried out to compare CTLM and mammography [5]. All the women who had undergone mam-mography were classified according to the Breast Imaging Reporting and Data System (BI-RADS) into a heterogeneously dense breast (BI-RADS 3) or an extremely dense breast group (BI-RADS 4). The data from this trial indicated that the CTLM evaluation was not affected by tissue density in breasts and could provide information about angio-genesis in most malignant and a few benign breast lesions. When CTLM was used as an adjunct to mammography in heterogene-ously dense and extremely dense breasts the sensitivity increased significantly.

References 1. Jemal A et al Global Cancer statistics CA Cancer J

Clin 2011 Feb 4.2. Poellinger A et al. Near-Infrared laser computed tom-

ography of the breast. Acad Radiol 2008; 15:1545.3. Saslow D et al. American Cancer society guide-

lines for breast screening with MRI as an adjunct to

mammography. CA Cancer J Clin 2007; 57: 75.4. Van de Wiele et al. Tumor angiogenesis pathways:

related clinical issues and implications for nuclear medicine imaging. Eur J Nucl. Med 2002; 29: 699.

5. Jin Qi, Zhao Xu-iang Ye, Run Xiao Bao & Milne ENC, personal communication


Practical application of CTLM

The CTLM system functions like a conventional CT scanner in that an energy source, in this case a Near-Infrared (NIR) laser, scans the breast; computed algorithms reconstruct cross-sectional images based on the measured optical data. The measured optical values are directly related to the optical effective transport coefficient of the breast tissue. Like CT, the images may be viewed as single slices or as 3D volumes. The patient lies face down in a comfortable position so that the breast to be examined is suspended through the circular aperture within the scanning bed. Nothing touches the breast; there is no compression and there is no ionising radiation since a laser is used as the energy source instead of the usual X-ray tube. The CTLM system produces 3-dimensional coronal, sagittal and axial cross-sectional images that display the distribution of haemoglobin within the internal structures of the breast. When interpreted by a trained and certified physician, the images provide images of high value in diagnostic determination.

Carestream Health is running a series of free Digital Mammog-raphy self-assessment workshops to help healthcare professionals acquaint and train themselves in digital mammography reading. Held on Saturday 5th and Sunday 6th March in the Austria Centre, the workshops will be facilitated by eminent clinicians Professor Roland Holland from the National Expert and Training Centre for Breast Cancer Screening, Radboud University Medical Cen-tre, Nijmegen, the Netherlands and Professor Ulrich Bick, MD, Department of Radiology, CCM, Charité-Universitätsmedizin, Berlin, Germany.Participants may register for up to seven one-hour sessions. Each

session starts with a short introduction that includes the learning objectives, the method of soft-copy reading and self-assessment, and instruction on how to use the system. Participants will have 45 minutes to read the cases, then assess their own performance. Cases may be discussed in detail with the medical experts. Each module contains 30 selected screening mammography cases with a mix of biopsy proven positives and negatives. The modules are independ-ent of each other and do not need to be completed sequentially. Participation is limited and early registration is advised. Visit www.carestreamhealth.com/ecr for details of how to register on-line.

Carestream Health offers free hands-on mammography experience at ECR 2011

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Oral care range to protect against vAPVentilator Associated Pneumonia (VAP) is a growing concern in modern hospital environments. Many recent studies suggest that it is possible to significantly reduce the risk of aspiration pneumonia by perform-ing basic patient oral hygiene. An extended range of oral care products is now available from Intersurgical to target VAP. These include OroCare Mini, an extra small toothbrush for targeted cleaning. Designed with a small atraumatic brush head and soft bristles, this brush also features a long

curved neck, which allows the user to reach all areas of the oropharynx. The brush is ideal for paediatrics and those with chal-lenging oropharyngeal situations. OroClean Complete is a convenient pack designed for use on those requiring a lit-tle more attention, such as elderly patients, patients in longer term care or patients with specific requirements.

OroCare 2 has a product handle that acts as a reservoir for the separately available anti-bacterial mouthwash vials. The mouthwash is released by gently squeezing the handle whilst carefully brushing the patient’s teeth with the soft atraumatic bristles. Standard suction tubing may be attached to the end of the handle and can be controlled by a com-fortably located thumb hole.OroCath is a single use oropharyngeal cathe-ter for oral suctioning during and in-between treatments. The flexible catheter extends all the way to the ET tube cuff and allows for oral hygiene in hard-to-reach places.Finally OroCare tooth gel is available in single doses for use with any Oral Care toothbrush systems.

IntERSuRGIcal Wokingham, Berks, uK www.ihe-online.com & search 45786

an event of the

ProdUCt NEWs 35 – march/April 2011

Oral and nasal suction device

Developed for neonatal and paediatric patients, the Neotech Little Sucker is one of the most efficient oral and nasal suc-tion devices available. With its soft, flexible tip, it is extremely gentle, and the thumb port allows for intermittent, single-handed suctioning. The product is ideal for use in NICU, PICU, respiratory and L&D depart-ments. Available in four sizes to accommo-date different sizes of patients, the small-est size is suitable for very tiny premature babies. The device is ideal for oral and nasal suctioning in the nursery (labour and delivery), neonatal intensive care, paediat-ric intensive care and emergency depart-ments. The clear handle allows visualisa-tion of secretions, and the large opening allows suction of very thick secretions.

MEdcoRP IntERnatIonal laguna Hills, ca, uSa www.ihe-online.com & search 45782

Patient monitors

Featuring cutting-edge innovations and impeccable craftsmanship, Omni Express patient monitors are the perfect choice for healthcare professionals who demand precision, performance and afford-ability. Enabling effective monitoring of ECG, respiration, SpO2, NIBP and tem-perature, the monitors provide for better patient care by allowing conditions to be

evaluated quickly and accurately. Two or three waveforms can be displayed with simultaneous multi-lead ECG monitor-ing. The monitor allows advanced ST and arrhythmia detection and quick BP read-ings recall. Graphical and tabular trend-ing is enabled, and audible and visual alarms are provided. A number of avail-able options include EtCO2 and optional printer. A battery back-up is provided.

InfInIuM MEdIcal, Inclargo, fl, uSa www.ihe-online.com & search 45783

Electrical safety analyser

The ESA620 Electrical Safety Analyzer, featuring smart technology to enhance productivity under any standard, is a port-able electrical safety tester. With selections of three test loads, two protective earth test currents and two insulation test voltages, this versatile device performs all primary electrical safety tests as well as several addi-tional leakage tests for premium standards compliance worldwide. A convenient 20 A device receptacle broadens the range of equipment that can be tested. Standard 2-wire and optional 4-wire protective earth measurement capabilities offer first-rate time savings, while DSP technology offers better accuracy of leakage measurements throughout specified ranges. Equipped with ten unique safety-enhanced ECG posts, the safety analyser offers simulation of ECG and performance waveforms so both electrical safety and basic tests on patient monitors can be performed with a single connection. When combined with optional Ansur computer-based software, the safety analyser allows for test procedure automa-tion, the capture of results and comparison to standard limits, printed reports, and total digital data management.

fluKE BIoMEdIcalEverett, Wa, uSa www.ihe-online.com & search 45784

Printers for high-quality medical images

Carestream Health has launched new printers that address the diverse printing needs of healthcare providers across the globe. Showcased as a work-in-progress, the CARESTREAM DRYVIEW CHROMA Imager is a general purpose device that will enable facilities to print high quality, low cost greyscale and colour images from a variety of modalities to paper or medi-cal film. The device can be linked to PACS and to image-enabled EMR systems and provides outputs of up to 200 prints an hour to film at a resolution of 650 pixels-per-inch for every image. This high reso-lution output meets the requirements for digital mammography (CR or FFDM) as well as traditional modalities.The compact device delivers desktop output of CR, DR, MRI and CT exams onto medical film, and combines high quality and reliability with low operating costs.

caREStREaM HEaltHRochester, nY, uSa www.ihe-online.com & search 45781

[email protected]

DISTRIBUTORS WANTEDAUSTRALIAN MADE ECG

USB - PC Based ECG

> 12 Lead Real Time Display> Reports and Diagnostics> Special Introductory Price> Small & Compact> Free Worldwide Shipping



Patient beside terminalThe all-in-one interactive Infotainment bedside ter-minal makes hospital stays easier by providing the same multimedia enter-tainment and commu-nication choices patients would enjoy at home, such as telephone, TV, radio,

movies, games and the internet. The patient experience is enhanced by intranet access, providing them with access to relevant education on their condition, information on their care-giver team, and hospital information, as well as helping them keep in touch with family and friends through video-conferencing, Skype, and instant messaging. The patient terminal also benefits medical staff by providing secure access to electronic patient data with an optimised hospital work-flow. As an aid to professional diagnosis, the terminal can remotely retrieve electronic patient records, access databases from the bedside and comply with Hospital Information Systems (HIS) requirements. Hospital administrators will see increases in operational efficiencies, increased patient and visitor satisfaction, and improved quality of care, while boosting profitability.

advantEcH EuRoPEfeldkirchen, Germany www.ihe-online.com & search 45778

Digital detectorDesigned to be cost-effec-tive and with high perform-ance, the Pixium RAD 4143 is a large-format, flat-panel digital detector that gen-erates high quality X-ray images in real time and

with low exposure, for immediate diagnosis. The detector is available with either caesium iodide (Pixium CsI) or Gadox X-ray detection technology. Its simplified design greatly facilitates its integration in X-ray systems. The detector is supplied either in an Ethernet compat-ible version, including preprocessing, or as part of a complete turnkey imaging sub-system, the PrestoDR, which provides clinical quality images. Comprising one or two detectors, a digital imaging worksta-tion and interfaces with generator, collimator and dose management module, PrestoDR delivers outstanding quality images within a few seconds to significantly improve productivity in any radiology room. DICOM compatibility ensures easy integration in a PACS network.

tHalESvelizy, france www.ihe-online.com & search 45774

Foetal monitorWith its brand new design, colour screen and enhanced functionality, the F3 foetal monitor reliably addresses the needs of obstetric departments in doctors’ offices, clinics and hospitals. Offering an exten-sive set of external fetal care monitoring parameters such as FHR, TOCO as well as foetal movement, the instrument is compact, portable and easy to use with enhanced user functionality. A powerful backup memory and long lasting rechargeable battery facilitate use. The start button on the front panel can be configured to integrate patient information and enable printing, simplifying the workflow. Three different display modes allow the selection of the one most appropriate for clinical needs. The 12 hours data storage, rechargeable battery allowing seven hours use and the Insight data management software enable the monitor to be used in outpatient departments and during house calls.

Edan InStRuMEntSShenzhen, china www.ihe-online.com & search 45775

Breast angiographyGE Healthcare’s new SenoBright1 Contrast Enhanced Spectral Mammography (CESM) technology is designed to allow physi-cians to image blood flow through angiography of the breast using a contrast agent and a dual energy acquisition technique. Con-trast agents can be used to highlight angiogenesis, the growth of small blood vessels potentially related to the presence of cancer. In addition to typical mammography images that show breast tis-sue density, CESM technology is designed to provide doctors with images of contrast uptake, which may indicate angiogenesis. SenoBright uses X-rays at multiple energies to create two separate exposures. These resulting images specifically illuminate and high-light areas where there is contrast uptake and potentially angiogen-esis. As mammography mainly images tissue densities, SenoBright

Software to customise QA

The development goal in the creation of Ocean QA software, a powerful tool that allows users to customise their Quality Assur-ance, was to create a smart and quick product incorporating the best features of existing software as well as new features. The new software creates a solid foundation for organising user and equip-ment information, measured data and test analyses. It provides an easy-to-view interface on the user’s laptop or netbook. Standard-ised measurements are easily created, not only for X-ray equip-ment, but also for the complete X-ray room. Attachments can be added, set-ups can be shared and global reports can be sent. The flexibility of the software allows the interface to be arranged as the user wishes, and the templates provided can be edited to include new columns, rows or analyses. The main templates can be saved as ”favourites”. Measured data and waveforms are easily stored for later viewing and it is always possible to make additional expo-sures. The software is specifically designed to faciliate use of RTI’s Piranha or Barracuda X-ray multi-meters, giving users access to the full power of these instruments in a very intuitive way.

RtI ElEctRonIcSMölndal, Sweden www.ihe-online.com & search 45773

ProdUCt NEWs 37 – march/April 2011

has been designed to produce an image that maps contrast uptake, adding the functional information to the conventional standard tissue density information of mammog-raphy. Doctors can highlight the prolif-eration of small blood vessels, potentially associated with cancerous tumour growth. Patients receive an intravenous injection of standard iodine contrast agent, and after

two minutes undergo a five-minute digital mammography exam. CESM images are acquired in familiar mammography views so that they can be correlated with standard results, facilitating interpretation by other specialists like surgeons or oncologists. CESM technology is intended to work as an upgrade to GE Healthcare’s Senographe DS and Senographe Essential digital mammography equipment.

GE HEaltHcaREBuc, france www.ihe-online.com & search 45796

Integrated MR/PET systemUntil now, it was nearly impossible to integrate MR and PET technolo-gies: the conventional PET detectors, which use photomultiplier tubes, could not be used in the strong magnetic

field generated by an MR system. Integration was further limited by the lack of space inside the MR device. For this reason, MR-PET imaging has to be the result of two separate scans (MR and PET) with a significant time lag. The Biograph mMR whole-body integrated MR and PET system allows simultaneous data acquisition. This revolu-tionary system comprises a MR scanner and an integrated PET detec-tion system with an architecture that performs as one. The new 3-Tesla hybrid system simultaneously captures MR and PET data with a whole-body system. With the simultaneous acquisition of MR and PET data, this system is designed to provide new opportunities for imaging. While MR provides exquisite morphological and functional details in human tissue, PET goes further to investigate the human body at the level of cellular activity and metabolism. The innovative system has the potential to be a particularly valuable tool for identify-ing neurological, oncological and cardiac conditions of disease and in supporting the planning of appropriate therapies. Since MRI does not emit ionising radiation, Biograph mMR may provide an added bene-fit with lower-dose imaging. The system also opens new opportunities for research, such as the development of new biomarkers or new ther-apeutic approaches. MR and PET have become an established part of everyday healthcare routines. The integration of these two technolo-gies into a single system capable of simultaneous acquisition brings the potential to revolutionise the diagnosis of many conditions. Initial research suggests that with this system, Molecular MR can scan the entire body in as little as 30 minutes for the combined exams, com-pared to one hour or more for sequential MR and PET examinations. A wide range of clinical applications is envisioned for molecular MR including the early identification and staging of malignancies, therapy planning (including surgery planning) and therapy control.

SIEMEnSErlangen, Germany www.ihe-online.com & search 45776

Adhesive for use with neonates

A flexible, new alternative to harmful tape on fragile neona-tal skin, NeoFlex Silicone Adhesive Roll is a unique adhesive, being easy to apply, adjust, remove as well as being an ideal skin barrier. The product can be used to secure limb boards and for a variety of other uses. The product is ideal for very small premature babies as well as older babies with sensitive skin. Conveniently packaged as a roll for single patient use, NeoFlex, like all of Neotech’s products, is latex and phthalate (DEHP) free.

nEotEcH PRoductS, Inc.valencia, ca, uSa www.ihe-online.com & search 45777

Summer Conference

Join us !

For more information contactEuropean Society of Intensive Care Medicine Rue Belliard 19 1040 Brussels, Belgium Tel: +32 2 559 03 71 Fax: +32 2 559 03 79 Email: [email protected] Internet: www.esicm.org

7-9 July 2011 Budapest, Hungary

Joint with

Perioperative Management State of the Art

Ad-BUDAPEST 2011-132x92.indd 1 10/02/11 15:03


Flat panel DR cassette Ideal for any clinical environment, the-FDR D-EVO flat panel DR cassette uses an innovative technology to provide clinicians with excellent image quality and outstand-ing flexibility. The cassette enables users to transition to DR without modification to the exam room. The lightest weight DR cassette of its size available, with a weight of only 2.8 kg, the 384 x 460 mm x 14 mm flat panel DR cassette provides portability to address lateral or other cassette-based

exams as needed, even in existing DR rooms. Another distinct advantage over competitive solutions includes a detach-able power supply, which eliminates the potential hazards of a tethered cord or concerns about battery life. The cassette represents the latest addition to Fujifilm’s impressive line-up of groundbreaking DR products. Featuring secure network con-nectivity, images are transmitted to the technologist workstation in only five sec-onds and cycle times are only nine second. The cassette uses the company’s patented ISS (Irradiation Side Sampling) to improve DQE (detective quantum efficiency) for outstanding image quality. This patented technology reduces the distance for light signals reaching the sensor, mitigating dif-fusion and attenuation for enhanced image sharpness and reduced noise. The result is FDR images with consistently high quality and increased diagnostic confidence.

fuJIfIlM EuRoPEdüesseldorf, Germany www.ihe-online.com & search

Windows developed for use in hospitalsSpecifically developed for use in hospitals, Safevent windows allow unrestricted natu-ral ventilation, reducing or eradicating the need for mechanical ventilation. The open-ing system is safe and secure, preventing access of intruders without the necessity for locks or keys. The anti-ligature locks prevent opening by patients if this is unde-sirable. They have easily cleaned rounded edges, and cannot be pulled off the win-dow. The entry of flies, wasps and vermin

is prevented, and the antibacterial surface also facilitates infection control.

BRItPlaS coMMERcIal WIndoWSWarrington, cheshire www.ihe-online.com & search 45732

Ultrasound systemOffering superior images of a con-sistent and uni-form quality, the E-CUBE 9 can allow accurate diagnosis, even on obese patients, providing fine and detailed image res-olution as well as superior penetra-tion. Single-crystal transducers are

now applied to three types of transducer: the single-crystal convex array (the larg-est radius of curvature), the single-crystal phased array and the innovative single-crystal 3D volume convex transducer. These transducers offer wide bandwidth and higher resolution images. The imaging technology of the ultrasound system offers excellent 2D images that are substantially enhanced through FleXcan (Flexible Scan architecture), a unique hardware structure and wide-bandwidth imaging technology, and FullSRI, an advanced image process-ing technology. Core features that optimise the workflow of the ultrasound system include a unique 17” wide LCD monitor that provides thumbnail images for instant review, a zoom reference view, an image parameter adjustment con-text menu to optimise the image quality and a user interface (UI) that is efficiently reinforced. For the convenience of both users and patients, the system provides an integrated gel warmer and anti-dust trans-ducer connector door.

alPIon MEdIcal SYStEMSSeoul, The Republic of South Korea www.ihe-online.com & search

CALENdAr oF EVENtsmarch 17-20, 2011KIMES 2011Coex, Seoul, KoreaTel. +82 2 551 0102Fax +82 2 551 0103e-mail: [email protected]

march 22-25, 201131st International Symposium on Intensive Care and Emergency Medicine (ISICEM)Brussels, BelgiumTel. +32 2 555 36 31Fax +32 2 555 45 55e-mail: [email protected]

march 29-31, 201114th SE-Asian Healthcare Show & ConferencesKuala Lumpur, MalaysiaTel +603 79 54 65 88 Fax +603 79 54 23 52 e-mail: [email protected]

April 4-6, 2011Hospital Build Europe 2011Nürnbergmesse, GermanyTel. +49 211 9686 3756Fax +49 211 9686 4756www.hospitalbuildeurope.com

April 6-8, 2011Med-e-Tel 2011Luxembourg, LuxembourgTel. +32 2 269 84 56Fax +32 2 269 79 53e-mail: [email protected]

April 13-14, 2011The 7th Annual World Health Care Congress Europe 2011Innovations and Best Practices to Improve European Health CareBrussels, BelgiumTel. +1 781-939-2559www.worldcongress.com/europe

may 10-13, 2011World of Health IT 2011Budapest, Hungarye-mail: [email protected]

may 9-13, 20114th International Congress of MyologyLille, FranceTel. +33 4 78 176 276http://myology2011.org/index_us.html

may 24-27, 2011Hospitalar 2011São Paulo, Brazilwww.hospitalar.com/ingles/

June 6-8, 2011UKRC 2011Manchester, UKTel. +44 20 7307 1406 / 11e-mail : [email protected]

June 7-9, 2011Medifest South AfricaCape Town, South Africawww.vantagemedifest.com

June 11-14, 2011 Euroanaesthesia 2011Amsterdam, The NetherlandsTel. +32 2 743 3290www.euroanesthesia.org

June 15-17, 2011IMDM (International Medical Distributor Meeting) - Cardiovas-cular & SurgeryBerlin, GermanyTel. +33 970 449564 e-mail: [email protected] www.imdmeeting.org

June 22 - 25, 2011CARS 2011 - Computer Assisted Radiology and SurgeryBerlin, GermanyTel: +49-7742-922 434e-mail: [email protected]

June 23-25 2011ESICM Summer Conference,: Mechanical ventilation – an UpdateTurin, Italye-mail: [email protected]

July 7-9, 2011ESICM Summer Conference: Periop-erative Management. State of ArtBudapest, Hungarye-mail: [email protected]

August 26-29, 2011 13th World Congress of the World Federation for Ultrasound in Medi-cine and Biology (WFUMB 2011)Vienna, AustriaTel. +43 1 535 13 05Fax +43 1 535 70 37e-mail: [email protected] www.wfumb2011.org

August 27-31, 2011ESC Congress 2011Paris, FranceTel. +33.4.92.94.76.00www.escardio.org/congresses/esc-2011

september 14-16, 2011Medical Fair Thailand 2011Bangkok, ThailandTel. +65 6332 9620 Fax +65 6332 9655e-mail: [email protected]

september 24-28, 2011ERS Annual Congress Amsterdam, The NetherlandsTel. +49 30 246 032 20Fax +49 30 246 033 99e-mail: [email protected]

october 1-5, 2011ESICM LIvES 2011 24th Annual Congress ICC-Berlin, GermanyTel. +32 2 559 03 71Fax +32 2 559 03 79e-mail: [email protected]

november 16-19, 2011MEDICADüsseldorf, Germanye-mail: [email protected]

november 27 – december 2, 2011RSNA 2011Chicago, IL, USATel. +1 630 571 2670www.rsna.org

dates and descriptions of future events have been obtained from usually reliable official industrial sources. iHE cannot be held

responsible for errors, changes or cancellations.

for more events see www.ihe-online.com/events/

IMAGIN

G DIAGNOSTIC SYSTE

MS, I

NC.

I D S I

SCAN

NING FOR LIFE

FORT LAUDERDALE, FLORIDA

Imaging Diagnostic Systems, Inc. • 5307 NW 35th Terrace • Fort Lauderdale, FL 33309 U.S.A.Tel: (1) 954-581-9800 • Fax: (1) 954-581- 0555 • www.imds.com • [email protected]

CAUTION: Investigational device. Limited by US Federal Law to investigational use. 820001.ECR

No CompressionNo Contrast Agent

No Ionizing RadiationNot Affected by Breast Density

The Computed Tomography Laser Mammography system is a non-invasive laser based imaging device that reveals the distribution of angiogenesis often associated with breast cancer.

CTLM® 1020

CT Laser BreasT ImagIng

Live

Demos at

ECR 2011

Stand

113FDA 510(k)

APPLICATION UNDER REVIEW


We image-enable Regional Care.

Well, not in Utopia, but all over the world we actually live in. We call it regional health imaging – market- proven

image and information management systems that implement multi-site integration up to the regional level.

Consolidating radiology, cardiology, nuclear medicine ... any department that produces images – so that you can

stay ahead of hospital and governmental requirements for sharing data and infrastructure. We offer a complete,

configurable, single-source solution that helps standardize disparate IT infrastructures and consolidate patient

records. Optimizing clinical resources, workflow and load balancing, reducing waiting times, and, ultimately,

saving costs. To everyone’s benefit. So, even though Utopia is not yet on our list, our integrated regional health

program has your current world covered.

We invite you to visit our booth at ECR 2011 for a demo! - EXPO A: BOOTH # 103

www.agfahealthcare.com/ecr2011

Where? In Utopia?

H e a l t h C a r eImaging Excellence, Clinical Confidence. We’ll take you there.

11128-E-InternationalHospital_210x297.indd 1 07/02/11 14:19


ihe_m-a_2011

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