2008-Issue05

EFSUMB Newsletter

EFSUMB Newsletter European Federation of Societies for Ultrasound in Medicine and Biology

Short news 3 In this issue we will highlight some of the events from the very successful EUROSON 2008 congress in Timisoara, more will follow in the December issue.

Also you will find many things from our very active Safety Committee.

3 The website for the next EUROSON meeting in Edinburgh has been launched. You will find lots of information on www.euroson2009.org and you can register your interest.

3 The impact factors for 2007 was released a few months ago. The impact factor for Ultraschall in der Medizin/European Journal of Ultrasound increased to 2.303 3 The Romanian society will join bulk subscription of the UiM/EJU beginning with the first issue in 2009.

3 The latest issue of ECHOES - the newsletter from WFUMB - can be found on www.efsumb.org under publications, and also on www.wfumb.org Michael Bachmann Nielsen

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tyimaging.com/pdf/prescribinginfo.pdf, http://md.gehealthcare.com/shared/ pdfs/pi/optison_pi.pdf).

Bubble trouble?

Gail ter Haar

On October 10th 2007, the FDA requested that a "Boxed Warning and other warnings emphasizing the risk for serious cardiopulmonary reactions be added to the labeling for ultrasound micro-bubble contrast agents used in echocardiography and that use of these products be contraindicated in patients with unstable cardiopulmonary status, including patients with unstable angina, acute myocardial infarction, respiratory failure, or recent worsening congestive heart failure" [FDA 2007]. The background for this warning was that the FDA had "received reports of deaths and serious cardiopulmonary reactions following the administration of ultrasound micro-bubble contrast agents used in echocardiography. Four of the 11 reported deaths were caused by cardiac arrest occurring either during infusion or within 30 minutes following the administration of the contrast agent; most of the serious but non-fatal reactions also occurred in this time frame." One patient died during a stress test, two patients were in severe heart failure, and the fourth was a ventilated patient who had severe respiratory failure and pulmonary emboli.

There has, understandably, been considerable discussion in the literature and at conferences, about this action. It has been pointed out (Grayburn 2008, Main et al 2007) that the FDA has responsibility for product safety, but that this is not necessarily the same as patient safety. Patient safety remains the responsibility of the clinician.

With more than 2 million ultrasound examinations using microbubble contrast agents (UCAs) having been carried out since their approval by the FDA 6 years ago, even if all these deaths can correctly Ultraschall in Med 2008; 29

be attributed to these bubbles, the associated risk is 1:500,000. This compares favourably with the 1:1000 mortality risk associated with diagnostic coronary angiography (Johnson et al 1989), and the 1:2500 risk of myocardial infarction or death with treadmill exercise testing (Stuart et al 1980). In a recent paper in which over 18,500 cases were studied, Kuznetsky et al (2008) were unable to show an increased mortality risk associated with contrast-enhanced examination, with 0.4% of hospitalised patients dying within 24 hours of echocardiography, but no statistical difference in mortality being seen between the group in which contrast agents were administered and that which received none.

In the light of this, and other information, the FDA's Cardiovascular and Renal Drugs advisory committee met in June 2008 to discuss the situation. The briefing document (which is available at http:// www.fda.gov/ohrms/dockets/AC/08/ briefing/2008-4369b1-01.pdf ) states that "FDA has finalized the risk management plan with the manufacturer of Definity and has approved labeling changes that remove most of the contraindications cited in the October, 2007 modification, as well as focused monitoring procedures upon patients with underlying pulmonary hypertension or unstable cardiopulmonary conditions. FDA is working with the manufacturer of Optison to effect similar changes to the label and to finalize a risk assessment and management program." This document also states that concern remains about the accumulating safety data for ultrasound contrast agents, and that products should continue to show a boxed warning highlighting "the risk for serious cardiopulmonary reactions". These contrast agents are now contra-indicated only for patients with rightto-left, bi-directional, or transient rightto-left cardiac shunts, and those with hypersensitivity to perflutren. The boxed warning has been modified to include the instruction " In patients with pulmonary hypertension or unstable cardiopulmonary conditions, monitor vital sign measurements, electrocardiography and cutaneous oxygen saturation during and for at least 30 minutes after DEFINITY速/ Optison administration" (http://www.defini-

Echocardiology remains the examination of choice in patients who are sufficiently ill to warrant invasive cardiovascular investigation. This therefore makes it difficult to differentiate between "association" and "cause" of any adverse events. It is useful in this context to examine the existing contrast agent safety literature.

This has recently been reviewed by both the World Federation of Societies for Ultrasound in Medicine & Biology (WFUMB) (Blomley et al 2007, Dalecki 2007) and the American Institute of Ultrasound in Medicine (2008, Miller et al 2008).

Blomley et al (2007), in a WFUMB report, concluded that while there is incomplete knowledge about the potential risk from clinical use of UCAs, they are extremely safe, with a low incidence of side effect.

There is no evidence that they are nephrotoxic or cardiotoxic, and result in a much lower incidence of hypersensitivity or allergic events than current X-ray or MR contrast agents.

There appears to be a consensus that an MI value of 0.4 represents the threshold above which bio-effects are seen in bio-effects studies in vivo [Miller et al 2008].

Above this level, bio-effects appear to increase rapidly with both increasing acoustic pressure amplitude and UCA concentration. Effects studied include premature ventricular contractions and petechial haemorrhage. The cells that are most susceptible to damage from diagnostic ultrasound exposure to UCAs are phagocytic cells that have engulfed the microbubbles. In many cases, the damage may be reparable, and the clinical implications of such findings are not known.

Good practice would, however, suggest caution when using UCAs. The AIUM recommends that for ultrasound examinations involving MI values greater than 0.4, the minimum UCA dose and ultrasound exposure consistent with acquisition of good diagnostic information should be used (AIUM 2008,2002). This reinforces the need for the practitioner to be aware of the safety indices (MI and TI) being used for any ultrasound examination. An initial (default start up) setting of MI of less than 0.4 for contrast enhanced ultrasound examinations is recommended.

EFSUMB Newsletter

EFSUMB's position is contained in its current safety statement (EFSUMB 2008):

Ultrasound contrast agents (UCA) 5 These usually take the form of stable gas filled microbubbles, which can potentially produce cavitation or microstreaming, the risk of which increases with MI value.

Data from small animal models suggest that microvascular damage or rupture is possible. Caution should be considered for the use of UCA in tissues where damage to microvasculature could have serious clinical implications, such as in the brain, the eye, and the neonate. As in all diagnostic ultrasound procedures, the MI and TI values should be continually checked and kept as low as possible. It is possible to induce premature ventricular contractions in contrast enhanced echocardiography when using high MI and end-systolic triggering. Users should take appropriate precautions in these circumstances. The use of contrast agents should be avoided 24 hours prior to extra-corporeal shock wave therapy.

References 1 AIUM Bioeffects of Diagnostic Ultrasound with Gas Body Contrast Agents 2002 http:/ /www.aium.org/publications/statements/ _statementSelected.asp?statement=25 2 AIUM American Institute of Ultrasound in Medicine consensus report on potential bioeffects of diagnostic ultrasound. J. Ultrasound Med 2008;27:503-515 3 Blomley M, Claudon M, Cosgrove D WFUMB symposium on ultrasound contrast agents: clinical applications and safety concerns.

Ultrasound in Med. & Biol. 2007; 33:180186 4 Dalecki D WFUMB symposium on ultrasound contrast agents: Bioeffects of ultrasound contrast agents in vivo . Ultrasound in Med. & Biol. 2007; 33:205-213 5 EFSUMB (2006) Clinical safety statement http://www.efsumb.org/ecmus/ClinicalSStatement-202006.pdf 6 FDA (2007) Information for Healthcare ProfessionalsMicro-bubble Contrast Agents (marketed as Definity (Perflutren Lipid Microsphere) Injectable Suspension and Optison (Perflutren Protein-Type A Microspheres for Injection) http://www.fda.gov/ CDER/drug/InfoSheets/HCP/microbubbleHCP.htm 7 Grayburn PA Product Safety" Compromises Patient Safety (an Unjustified Black Box Warning on Ultrasound Contrast Agents by

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the Food and Drug Administration). The American Journal of Cardiology 2008;101:892 - 893 Johnson LW, Lozner EC, Johnson S et al Coronary arteriography 1984–1987: a report of the registry of the Society for Cardiac Angiography and Interventions. I. Results and complications. Cathet. Cardiovasc, Diagn.

1989;17:5-10 Kusnetzky LL, Khalid A, Khumri TM, Moe TG, Jones PG, Main ML Acute Mortality in Hospitalized Patients Undergoing Echocardiography With and Without an Ultrasound Contrast Agent J.Am.Coll.Cardiol.

2008;51:1704–1706, Main ML, Goldman JH, Grayburn PA Thinking Outside the "Box" - The ultrasound contrast controversy. J. Am. Coll. Cardiol.

2007; 50:2434–2437 Miller DL, Averkiou MA, Brayman AA, Everbach EC, Holland CK, Wible JH, Wu J Bioeffects considerations for diagnostic ultrasound contrast agents. J. Ultrasound Med 2008;27:611-632 Stuart RJ, Ellestad MH. National survey of exercise stress testing facilities. Chest 1980;77:94–97

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Clinical Safety Statement for Diagnostic Ultrasound – (2008) This document is the 2008 revision of the EFSUMB Clinically Safety Statement. A Safety Statement has been published by EFSUMB annually since 1994. The text is deliberately brief, and gives a concise overview of safety in the use of diagnostic ultrasound. The 2008 Statement is the fifth revision of the Statement, the previous revisions being those published in 1998, 2002, 2003 and 2006.

Clinical Safety Statement for Diagnostic Ultrasound 5 Diagnostic ultrasound has been widely used in clinical medicine for many years with no proven deleterious effects. However, if used imprudently, diagnostic ultrasound is capable of producing harmful effects. The range of clinical applications is becoming wider, the number of patients undergoing ultrasound examinations is increasing and new techniques with higher acoustic output levels are being introduced. It is therefore essential to maintain vigilance to ensure the continued safe use of ultrasound.

Ultrasound examinations should only be performed by competent personnel who are trained and updated in safety matters.

It is important that ultrasound devices are appropriately maintained.

Ultrasound produces heating, pressure changes and mechanical disturbances in tissue. Diagnostic levels of ultrasound can produce temperature rises that are hazardous to sensitive organs and the embryo/ fetus. Biological effects of nonthermal origin have been reported in animals but, to date, no such effects have been demonstrated in humans, except when a microbubble contrast agent is present.

The Thermal index (TI) is an on-screen guide to the user of the potential for tissue heating. The Mechanical index (MI) is an on-screen guide of the likelihood and magnitude of nonthermal effects. Users should regularly check both indices while scanning and should adjust the machine controls to keep them as low as reasonably achievable (ALARA principle) without compromising the diagnostic value of the examination. Where low values cannot be Ultraschall in Med 2008; 29

achieved, examination times should kept as short as possible. Guidelines issued by several ultrasound societies are available.

and is used prudently by fully trained operators. This includes routine scanning of pregnant.women.

Some modes are more likely than others to produce significant acoustic outputs and, when using these modes, particular care should be taken to regularly check the TI and MI indices. Spectral pulse wave Doppler and Doppler imaging modes (colour flow imaging and power Doppler imaging) in particular can produce more tissue heating and hence higher TI values, as can B-mode techniques involving coded transmissions. Tissue harmonic imaging mode can sometimes involve higher MI values. 3D (three dimensional) imaging does not introduce any additional safety considerations, particularly if there are significant pauses during scanning to study or manipulate the reconstructed images.

However, 4D scanning (real-time 3D) involves continuous exposure and users should guard against the temptation to prolong examination times unduly in an effort to improve the recorded image sequence beyond that which is necessary for diagnostic purposes.

The power levels used for fetal heart rate monitoring (cardiotocography - CTG) are sufficiently low that the use of this modality is not contra-indicated on safety grounds, even when it is to be used for extended periods.

Ultrasound exposure during pregnancy 5 The embryo/fetus in early pregnancy is known to be particularly sensitive. In view of this and the fact that there is very little information currently available regarding possible subtle biological effects of diagnostic levels of ultrasound on the developing human embryo or fetus, care should be taken to limit the exposure time and the Thermal and Mechanical Indices to the minimum commensurate with an acceptable clinical assessment.

Temperature rises are likely to be greatest at bone surfaces and adjacent soft tissues.

With increasing mineralisation of fetal bones, the possibility of heating sensitive tissues such as brain and spinal cord increases. Extra vigilance is advised when scanning such critical fetal structures, at any stage in pregnancy. Based on scientific evidence of ultrasound-induced biological effects to date, there is no reason to withhold diagnostic scanning during pregnancy, provided it is medically indicated

Safety considerations for other sensitive organs 5 Particular care should be taken to reduce the risk of thermal and non-thermal effects during investigations of the eye and when carrying out neonatal cardiac and cranial investigations.

Ultrasound contrast agents (UCA) 5 These usually take the form of stable gas filled microbubbles, which can potentially produce cavitation or microstreaming, the risk of which increases with MI value.

Data from small animal models suggest that microvascular damage or rupture is possible. Caution should be considered for the use of UCA in tissues where damage to microvasculature could have serious clinical implications, such as in the brain, the eye, and the neonate. As in all diagnostic ultrasound procedures, the MI and TI values should be continually checked and kept as low as possible. It is possible to induce premature ventricular contractions in contrast enhanced echocardiography when using high MI and end-systolic triggering. Users should take appropriate precautions in these circumstances and avoid cardiac examinations in patients with recent acute coronary syndrome or clinically unstable ischaemic heart disease. The use of contrast agents should be avoided 24 hours prior

EFSUMB Newsletter

Dr. Ismail Mihmanli

EFSUMB Newsletter meets Turkey Facts: 5 3 3 3 3 3 3

Area: 783,562 km2 Largest city: Istanbul Population: 13 million Capital:Ankara Population:4.5 million EFSUMB members:283

Turkey joined EFSUMB in 2005. The current interview between the delegate of the Turkish Ultrasound Society Dr. Ismail Mihmanli and the Editor of the EFSUMB Newsletter, Professor Michael Bachmann Nielsen, took place in August 2008. Ismail Mihmanli is Head of the Ultrasound and Doppler Division at the Radiology Department of Cerrahpasa Medical School in Istanbul University. A professor in Radiology, with the subspeciality Doppler ultrasound he has been the Turkish delegate to EFSUMB since the Society of Medical Ultrasonography joined EFSUMB in 2005.

The Turkish Ultrasound Society was formed around 1980. "Our society is multidisciplinary but the main part of members is radiologists. I will expect that more than one thousand radiologists could be available for membership. Few gastroenterologists are members and few of them do perform ultrasound, maybe because the workload of patients is so large that one can save time to set patients to ultrasound examinations elsewhere."

southwest, neighbouring 7 countries.

"Does the size of the country give any language problems and which language do you speak?" "Not really", Mihmanli says, "Turkish is the only official language and everyone in Turkey speaks that language.

There may be some parts of the country where another dialect is spoken but Turkish is always spoken as the official language and it is the language you are taught in school. In elementary school you are offered second language, which is most often English, but it could be German or French. Personally I did not learn English until I went to the university, and English is the only other language I speak except Turkish. I do not know any of the languages from our neighbouring countries."

"As you know the official journal of EFSUMB is the European Journal of Ultrasound and I know that you personally have published in that journal. Do you think that the Turkish Society will at some time take on the journal?" "The problem is the English language", Ismail Mihmanli says, "doctors at university hospital will have a certain experience in the English language and will be able to read English but many doctors outside of university hospital will have difficulty in understanding the scientific content."

Board of Directors of Turkish Ultrasound Society. Left to right; Prof Deniz Akata, Prof Adnan Kabaalioglu, Prof Mustafa Ozmen, Prof Enis Igci, Prof Ismail Mihmanli, Prof Mustafa Secil, Prof Sureyya Ozbek.

Turkey has a training programme similar to many other European countries. "After finishing medical school there is a mandatory 2 years service in government hospital, you have to draw a place name, like in a lottery, and this name decides which hospital in the country you would have to go to. The specialist training takes 4-5 years. To become a specialist in Turkey you have to pass an exam", Dr. Mihmanli says. "The Health Ministry has recently acknowledged that the numbers of doctors are lower than it should be and this year the uptake in medical students was increased 25%."

Turkey is a very large country, extending about 1,600 kilometres southeast to northwest and 650 kilometres northeast to

Istanbul where continents meet; the magnificient view of Bosphorous from the helicopter.

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The Turkish society holds annual courses, all held entirely in the Turkish language.

"We can hold a course in English, inviting speakers from other countries and mainly from our universities who can give lectures in English as well. But we have to organize simultaneous translation from English to Turkish at this kind of course. As you know, this will increase organization cost. In addition, audience prefer courses to be held in Turkish. This year in April we held a course in obstetric ultrasound in Ankara, we will hold a course with the same subject once again in Antalya in September. In general, course subject is determined according to audience questionnaire which we took at the end of each course.

The 2009 meeting will also be in Ankara in the spring. We often choose Ankara to our courses because it is the government city with lots of hotels, and also it is located central in the country so that many will be able to come by car."

There is not a dedicated newsletter for the society, correspondence goes out by using e-mail and is also posted at the website of the society www.tud.org.tr. Courses and meetings are also to be found at the radiology website www.turkrad.org.tr.

Last year the Turkish society lost a bid to host the EUROSON congress in Istanbul.

However Turkey is increasingly popular as a location for congresses. Both ESGAR and CIRSE have already held successful congresses in Turkey, perhaps EUROSON will be next?

Poster prizes at EUROSON 2008 3 First Prize was awarded To Jordan Genov , Bulgaria for his poster titled " Factors Influencing Complete Tumour Destruction, Local Tumour Progression And Survival After Radiofrequency Ablation Of Metastatic Liver Tumours.

3 Second Equal Prizes were awarded to Anca Ciurea, Romania for his poster titled "Sources Of Error In Breast Us Elastography" and to Florin Brezan , Romania for his poster titled "Septo-Optic Dysplasia (Demorsier's Syndrome) - A Case Report".

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Therese Planiol lecture at EUROSON 3 Launched a foundation for brain research At the 20th EUROSON held in Timisoara, Romania on the 3 June 2008, Prof Franรงois Tranquart presented the Terese Planiol Lecture titled " Ultrasound Contrast Agents: from diagnostic to therapeutic applications".

Professor Therese Planiol.

This lecture has been held at every EUROSON since 1996 under the sponsorship of SFAUMB, the French society in honour of Professor Therese Planiol.

3 Pioneer in Nuclear Medicine and Ultrasound 3 Founder of SFAUMB (with L Pourcelot): 35 yrs existence 3 Past-director of Nuclear Medicine and Ultrasound Dept in Tours

Prof Franรงois Tranquart and Prof David H Evans

Young investigators award at EUROSON 2008 This year entries were: Roland Syha from Germany, Fulvia Terracciano from Italy, Dan Ionut Gheonea from Romania, Richard G.P. Lopata from The Netherlands and Andrew Mcqueen from the United Kingdom.

First prize was awarded to Richard G P Lopata for the abstract titled "4D Cardiac Strain Imaging for diagnosis of chronic heart failure".

CV Richard Lopata was born in 1980 in Oosterhout, the Netherlands. He received his M.Sc. degree in BioMedical Engineering at the Eindhoven University of Technology in 2004. His graduation project 'Identifiability of Pharmcokinetic Parameters in Dynamic Contrast-Enhanced MR Imaging for Measurement of Tumor Perfusion' resulted in two peer-reviewed papers. He started his PhD-project in Nijmegen in November 2004. The project is entitled '3D Ultrasound Imaging Techniques for the Detection of Chronic Heart Failure in Children" and is still in progress. Richard's

Richard GP Lopata

primary research interests are Strain Imaging, 3D ultrasound, Echocardiography, Signal processing and BioModeling.

Abstract: Title: 4D Cardiac Strain Imaging for diagnosis of chronic heart failure.

Cardiac strain imaging has been assessed as a non-invasive technique for mapping the mechanical properties of myocardial tissue and monitoring cardiac diseases, such as fibrosis and infarction. The intro-

EFSUMB Newsletter

duction of real-time 3D ultrasound imaging has boosted research in 3D strain imaging. The complex heart movements and deformations require 3D+t data for accurate assessment of strain in all directions. Sub-optimal temporal resolution of 3D datasets is still a problem. In this study, BiPlane and full 3D volume imaging are used for measuring cardiac strain in 3 orthogonal directions and their application to detect chronic heart failure. Two- and three-dimensional strain imaging techniques, suitable for phased array data, were developed using the raw frequency data of the ultrasound systems. The strain estimation and tracking techniques were validated using simulated linear and phased array ultrasound data and gelatin phantoms of tumor and vessel phantoms.

The rf-based techniques outperformed speckle tracking techniques at finer scale.

In a pilot animal study, four beagles with an induced valvular aortic stenosis were monitored. The valvular aortic stenosis results in a chronic pressure overload (30 - 200 mmHg respectively) of the left ventricle. This leads to hypertrophy and finally fibrosis. Raw (RF) ultrasound data were acquired with a Philips SONOS 7500 live 3D ultrasound system, equipped with a X4 matrix array transducer and an RF-interface. Using ECG-triggered BiPlane imaging (frame rate = 100Hz), frame-to-frame translations and deformations of the heart (infero-lateral wall of the left ventricle) in three orthogonal directions were obtained over the heart-cycle. Radial strains, circumferential and longitudinal strains were measured in the beagles. In all dogs, both radial strain images and mean strain curves were identical and the variance between the radial strains of these two independent planes was relatively small (35 % ± 5.7 %) . The lateral and elevational maximum strain was considerable lower (approximately 20% and 30% respectively) and in opposite direction. The strain curves of the beagle with a pressure gradient of 200 mmHg showed decreased maximum strain values, which indicates stiffening of the ventricle as corroborated with histology. In conclusion, measuring deformation in three directions in the heart is feasible using this rf-based approach.

Literature reviews GJ Vella, VF Humphrey, FA Duck, SB Barnett. The cooling effect of liquid flow on the focussed ultrasound-induced heating in a simulated foetal brain. Ultrasound in Med & Biol 2003; 29: 1193–1204, The aim of this paper was to study the cooling effect of fluid flow during ultrasound exposure of a test phantom designed to simulate human foetal skull and adjacent brain. In this well designed, and executed, study, a narrow 3.5 MHz pulsed ultrasound beam (5.7 µs pulse length; 8 kHz prf; 20–255 mW power) was used to expose a bone phantom that had similar thermal and acoustic properties to human foetal bone. Flow was through 2 mm diameter wall-less channels. This diameter was chosen as being typical of intracerebral vessels in the human foetus (1–3 mm).

Temperatures were measured using 50 µm thermocouples attached proximally and distally to the bone phantom in the ultrasound beam. It was found that the percentage cooling produced by the water was independent of source power, and its effect decreased with distance from the vessel, being negligible at 3mm.

The amount of cooling was found to increase with flow rate up to a level at which it saturated despite an increase in flow. It was therefore concluded that flow must be sufficiently slow to allow enough time for heat to be conducted across the surrounding tissue and thus convected away from bone. This has also been observed in animal studies.

Temperature rises of the order of 2.5 C were measured for 100mW exposures.

These were typically reduced by about 12% at the plateau of flow rate.

It is difficult to fully assess the clinical relevance of this study, except to say that temperatures indicated by the TIC may be reduced by a small amount when the ultrasound exposure is near large blood vessels, as might be expected. This is good from the safety viewpoint, but it is best to assume that such an effect will be negligible when doing a risk assessment.

Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moye LA, Hill MD, Wojner AW. Ultrasound-Enhanced Sy-

stemic Thrombolysis for Acute Ischemic Stroke. N Engl J Med 2004; 351: 2170– 2178.

Härdig BM, Persson HW, Gido G, Olsson SB. Does low-energy ultrasound, known to enhance thrombolysis, affect the size of ischaemic brain damage? J Ultrasound Med 2003; 22: 1301–8.

Thrombolysis using tissue plasminogen activator (t-PA) is the treatment of choice for acute myocardial infarction. A clinical trial conducted at the National Institutes of Health found clinical improvement after 24 hours and a better neurological outcome after three months when t-PA was administered for thrombolysis in acute ischaemic stroke. Since ultrasound is a means of dissolving a thrombus, the question arose as to whether the combination of t-PA and ultrasound would be more effective in acute ischaemic stroke. This was examined in a multi-centre controlled trial. Within three hours after the onset of stroke, a trained ultrasonographer measured the residual blood flow in the middle cerebral artery using an established grading system. Of the 126 patients enrolled, 63 were randomised to receive t-PA and two hours of 2 MHz pulsed ultrasound treatment with a maximal transducer output of 750 mW, the upper limit of the diagnostic energy range. The transducer was mounted in a head frame at a constant angle over the temporal bone. Unfortunately no detailed information about the actual output power at the selected insonation depths, nor were important exposure parameters such as pulse length and dwell time given. 63 control patients were positioned identically in the head frame and received t-PA but without the ultrasound exposure. Flow in the middle cerebral artery was graded in all patients after 30, 60, 90, and 120 minutes. The first criterion for assessment was how often the neurological deficit had improved or resolved after 24 hours, and the second the neurological status after three months.

Complete recanalisation or dramatic clinical recovery within two hours as assessed

by Doppler flow in the middle cerebral artery occurred in 31 patients treated with t-PA and ultrasound and in 19 patients treated with t-PA, but without ultrasound; the difference was statistically significant. A dramatic clinical recovery wiUltraschall in Med 2008; 29

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thin 24 hours was found in 24 patients after ultrasound treatment and in 21 patients with t-PA without ultrasound; this difference was not significant. The outcome after 3 months was similar in both groups.

Thrombolysis with t-PA is currently suitable for a subset of patients with acute ischaemic stroke: the interval between middle cerebral artery occlusion and start of lysis must be short, 20% of strokes are due to intracranial haemorrhage and are not suited to lysis. The therapeutic benefit of ultrasound and t-PA over t -PA only was significant yet not dramatic; additional studies with more patients should bring further clarity. One of the next issues to be addressed is the frequency of the ultrasound. The low MHz range gave less thrombolysis in vitro than 25–200 kHz ultrasound. Finally, the incidence of intracranial haemorrhage induced by ultrasound must be closely monitored since this complication has been observed in a recent European trial with low frequency transcranial ultrasound[1].

In another paper on this topic Härdig B et al (2003) investigated the size of the region of brain ischaemia following ultrasound exposure in rats, in a well established experimental model of cerebral ischaemia. After ligation of the external carotid artery, a 35 µm diameter filament was inserted into the internal carotid artery and pushed upward until it occluded a major branch of the middle cerebral artery. It stayed in place for 90 minutes before it was removed and the neck incision was closed. During the ischaemic period,

two cranial burr holes of 5 mm diameter were created in each animal to provide an acoustic window into the brain. A group of six rats was treated for an hour with a custom made 1 MHz transducer with a spatial average temporal average intensity of 0.1 mW cm-2 , a second group of six rats served as control and was not exposed.

The neurological deficit was scored after anaesthesia and the experiment terminated 24 hours later. The volume of the cerebral infarction caused by the arterial occlusion was calculated from serial histological sections.

The authors found volumes of the brain infarct ranging from 150–200 mm3 . These were similar both with and without ultrasound treatment with no significant difference between the groups.

The outcome of the experiment is positive since it supports the continuation of experiments on thrombolysis in the brain. The paper's title is a little misleading since it suggests that a thrombolysis experiment was done. It is, however, not known whether, in this experimental model a thrombus was formed in the occluded cerebral artery and its branches by placement of the filament and whether thrombolysis occurred. Further research would resolve this question.

Daffertshofer M., Gass A., Ringleb P., Sitzer M., Sliwka U., Els T., Sedlaczek O., Koroshetz W., Hennerici M. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: Increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator. Stroke 2005; 36:1441–1446

International Course in contrast enhanced Ultrasound/Euroson School The course is held in Hannover in Germany 6th – 9th November 2008. Detailed information about the course is now available at www.ceus-course.eu. You will find the programme, list of speakers and facul-

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ty and information on Hannover. On the website you will also find an image gallery of CEUS cases.

The programme can also be found at the EFSUMB website.

EFSUMB Newsletter

Sydney Australia, 30 August – 3 September 2009

Countdown to WFUMB 2009 World Medical Ultrasound Congress A Special Message From Host Society, ASUM.

ASUM has embarked on an active marketing strategy to promote and publicize this event worldwide so as to encourage and facilitate participation from as many international delegates as possible in this information and technology packed event.

It would be really helpful if EFSUMB members and friends of ASUM worldwide to help spread the word about the Congress, and to also refer to the website www.wfumb2009.com for ongoing updates and news. Also we need to encourage potential delegates to submit an abstract or poster, to exhibit, or to plan ahead to attend WFUMB 2009 to exchange ideas and information or simply to do business. The call for abstract will close on 28 November 2008. There are many prizes and awards available.

There is no doubt this will be a world class networking opportunity not to be missed.

The Congress will be held over five days from Saturday 30th August to Thursday 3rd September 2009 at the Sydney Convention and Exhibition Centre.

In the countdown to the WFUMB 2009 World Medical Ultrasound Congress, August 30 to September 3, 2009 we will be sending you regular e-Newsletters to keep you abreast of the latest news, remind you about deadlines for abstracts, registration and presentations and provide you useful tips for delegates from overseas traveling to Australia. Please send your email address to wfumb2009@ wfumb2009.com or go online to www.wfumb2009.com to register your interest in receiving these e-Newsletters.

We will also be giving you the latest news on our scientific program, profiles on keynote speakers and points of special interest.

The WFUMB 2009 World Congress in Sydney will be an amazing opportunity for delegates to network with colleagues from across the globe in one of the world's most beautiful settings - Sydney's Darling Harbor precinct.

This Congress, the most ambitious project ever taken on by the Australasian Society of Ultrasound Medicine (ASUM), will provide enormous scope for our participants'

to "touch and feel" the latest in technology and to hear and discuss the latest innovations from our world-class presenters.

I am particularly pleased to acknowledge the support of our major sponsors Toshiba, GE Healthcare, Medison and Philips. I also appreciate the support from Business Events Sydney and the Department of State and Regional Development.

It is predicted that the world market for medical ultrasound systems is expected to continue with its healthy, rapid growth from $3.97 billion in 2006 to more than $4.5 billion by 2010. This will also be helped by the annual growth in the Asian market.

In Australia, we are also seeing an increase in ultrasound Medicare schedule items, consistent with the increasing recognition of ultrasound technology as a valuable and popular medical diagnostic and procedural tool. It has applications in nearly every aspect of medicine and this helps in saving lives and improving health worldwide.

We are now opening the bookings of exhibition space to potential exhibitors from around the world. For enquiries about sponsorship and exhibition, please contact by email: sponsorship@icms.com.au or carolinehong@asum.com.au I look forward to welcoming you to Sydney for the experience of a lifetime. Go to the website www.wfumb2009.com and you will find useful tips on just about anything you need to know about Sydney, Australia, tourist destinations and if you cannot find the answer to something you need to know just contact me at carolinehong@asum.com.au or any of the ASUM team at asum@asum.com.au and we will make sure your questions are answered.

Dr Caroline Hong BDS(Uni Adel) Grad Dip HA(SA) MHA(Uni NSW) AFCHSE CHE FADI FSAE FAICD Chief Executive Officer, Australasian Society for Ultrasound in Medicine (ASUM) carolinehong@asum.com.au

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