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Volume 34 Issue 6 IHE November 2008

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What the future holds for Mrialso in this issue:Using non-natural amino acids for tumour imaging points to be considered before using poc blood gas analysers poc platelet function testing intelligent refrigerators for the safe dispensing of blood on demand

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End of the aspirin theory?It has long been established that, in patients with either diabetes mellitus or cardiovascular diseases and who have already had a cardiovascular accident such as a heart attack or a stroke, treatment by antiplatelet agents can significantly reduce the incidence of future cardiovascular events. Patients with peripheral artery disease who already have had such an accident and who then took antiplatelet agents are known to be 25% less likely to develop subsequent accidents. Although in fact most of the studies that generated these encouraging data used antiplatelet agents other than aspirin, it has been widely assumed that aspirin plays a significant role in secondary prevention. Not only that, but the strength of the data behind the secondary protective effects led to the proposal that aspirin could also be useful for primary prevention in high-risk patients, such as those with diabetes or asymptomatic peripheral arterial disease. This recommended use of aspirin has even been incorporated into the official guidelines of such august bodies as the American Heart Association, the American Diabetes Association and the American College of Cardiology. Since diabetic patients or those with peripheral arterial disease have a much higher morbidity and mortality than normal subjects (diabetics as much as two-to-five times greater), the hope was that if a similar benefit could be obtained for primary prevention as has been shown in the secondary cases, an overall significant health improvement could be obtained. If only.! The results of an extensive doubleblind, randomised, placebo-controlled trial involving no fewer than 1276 patients with diabetes or asymptomatic arterial disease have just been published (BMJ 2008;337:a1840) and unfortunately deal a hefty blow to the cherished hope that aspirin could work its magic just as well in primary as in secondary prevention. It was found that, in terms of the number of heart attacks and strokes suffered by at-risk patients there was absolutely no difference between patients taking aspirin compared to those taking placebo. While the current study in no way puts in doubt the role of aspirin in secondary prevention (and in fact the authors of the BMJ study go to great lengths to stress that such patients should continue their aspirin therapy) the whole question of primary aspirin prophylaxis is thrown into doubt. This is all the more important because of the nonnegligible side-effects of aspirin, particularly in terms of gastro-intestinal bleeding. Although the risk of major bleeding in an individual patient is still relatively small, the number of people taking aspirin is large and therefore, in population terms, aspirin-induced bleeding is a significant problem. Perhaps the greatest effect of the recent results is, however, likely to occur in the loss of confidence that hard-pressed front-line physicians will have in the use of officially recommended guidelines. When it turns out that the aspirin guidelines werent based on any hard data in the first place and now have been shown to be simply invalid, its hard not to lose trust in the system that generated the guidelines.

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ContentsfronT coVer prodUcTs[34] High resolution PEt/Ct [46] smart cable technology in multiparameter monitors [49] Handheld ECG systemRue des Palais 100 1030 Brussels, Belgium Tel. +32-2-240 26 11 Fax: +32-2-240 27 78 www.ihe-online.com Managing editors Alan Barclay, Ph.D. [email protected] Frances Bushrod, Ph.D. editor Ruth Knowles, BSc. editorial and advertising coordinator Anna Hyrkas circulation Manager Arthur Lger publisher/editor in chief Bernard Lger, M.D. advertising sales Manager Astrid Wydouw [email protected] Webmaster Damien Nol de Burlin2008 by PanGlobal Media bvba-sprl. Production & Lay-out by Studiopress Communication, Brussels. Circulation Controlled by Business of Performing Audits, shelton, Ct, UsA.The publisher assumes no responsibility for opinions or statements expressed in advertisements or product news items. The opinions expressed in by-lined articles are those of the author and do not necessarily reflect those of the publisher. No conclusion can be drawn from the use of trade marks in this publication as to whether they are registered or not.

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Point of Care UPdatePoC blood gas analysers: considerations before use Wireless technology: enhancing information management in PoC testing PoC platelet function testing

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MediCal iMagingWhat does the future hold for MrI? tumour imaging with radiolabelled non-natural amino acids. A selection of the latest products in the medical imaging field rsNA 2008 Preview: radiologys current status and future potential

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PoINt oF CArE UPdAtE

Point-of-Care blood gas analysers in cardiac surgery: considerations before usethe application of extracorporeal circulation during cardiac surgery has immediate effects on a patients haematology, chemistry and acid base balance, which carry over into post operative intensive care. these sudden and often dramatic alterations place emphasis on the need for point-of-care blood gas analysers that must not only reliable, but also should not be influenced by blood chemistry or viscosity. Most modern point-of-care blood gas analysers measure haematocrit using a technology called conductivity. other blood gas analysers measure haemoglobin only, using a technology called co-oximetry, and calculate the given haematocrit for that haemoglobin value. the differences between these two methods of analysis and their implications on red cell transfusion practice during and post cardiac surgery are reviewed in this article. are carried out using POC devices that use conductivity to obtain their results [1,2,3]. Due to the volumes and types of fluids used during cardiac surgery, condumetric measurements of haematocrit may give falsely low values that could trigger the clinician to prematurely transfuse that patient with banked blood. The inaccuracies in conductivitybased haematocrit can result from several variables that are common during the course of cardiopulmonary bypass. Co-oximetry is the preferred laboratory method of measuring haemoglobin when using blood gas analysers because of its precision in measuring the four haemoglobin moieties. In fact, as stated in the the book Clinical Application of Blood Gases By B.A. Shapiro [4] the co-oximeter is the most accurate method available for measuring the four clinically relevant haemoglobin moieties and is considered the standard against which all other methods must be compared. dynamics that occur in what is commonly called a controlled shock-like state. It is important to note that all POC blood gas analysers give their values for haematocrit based on conductivity, which is the ability of a fluid to allow an electric current to pass through it. The level of this electrical conduction in plasma is reduced as the amount of formed elements (red cells) increase in this fluid, which is thereby recorded as an increased haematocrit. Obviously, the opposite occurs when the formed elements in plasma are reduced. Measurements of haematocrit using conductivity did not become available to the clinician until the 1960s [5]. Conductivity-based haematocrit is considered reliable and accurate for most clinical situations and most physiologically normal patients. However, this is not the case in the cardiac surgery arena where the physiology is altered by a variety of fluids and fluid dynamics. During the latter case, the accuracy of haematocrits using conductivity is often flawed and affected by changes in sodium levels, changes in protein concentrations, the use of plasma volume expanders, the amount and types of anticoagulants used for bypass and even the presence of elevated white blood cell

conductivityCardiac surgery exposes the patient to a unique series of physiological changes due to the fluids used for maintenance of cardiopulmonary bypass, the exaggerated dosages of pharmaceuticals needed to maintain homeostasis and the alterations in fluid

by G. J. Myers

One of the most frequently overlooked instruments in the cardiac operating room (COR) and cardiovascular intensive care unit (CVICU), that can have an effect on a programmes overall transfusion rate, is the point-of-care (POC) blood gas analyser. All POC devices perform blood gas analysis with a high degree of reliability, but inaccuracies in measurements of haemoglobin/haematocrit during cardiac surgery can lead to some patients being unnecessarily transfused. POC analysers are usually located within the COR environment to allow for quick and accurate results of blood gas analysis, electrolytes and haematology. Some are marketed as hand-held and desktop devices, while others are portable devices that are designed to be moved from area to area. There are essentially two proven and reliable methods used by POC blood gas analysers: measuring the patients haematocrit (conductivity) or haemoglobin (co-oximetry) [Table 1]. However, caution must be exercised during cardiac surgery, when measurements of haematocrit

Open heart surgery with cardiopulmonary bypass.

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PoINt oF CArE UPdAtEManufacturerInstrumentation Laboratories Seimens Radiometer Copenhagen Abbott Laboratories International Technidyne Roche Group Nova BiomedicalSubstances other than haemoglobin can be found in a sample and may cause light to scatter and could create errors when using co-oximeters as well. The most common offenders are high lipids and cell fragments from incomplete haemolysis [4].

conductivityGem Premier 3000 Rapidpoint 400 ABL 77 I-STAT IRMA TRUPoint AVL Omni C Stat Profile pHOx

co-oximetryGem Premier 4000 Rapidpoint 405 ABL800 Not Available Not Available Omni S Separate machine

discussionThe many deleterious effects of red cell transfusion have been recently reported and include increases in morbidity and mortality [7,8]. During cardiac surgery the actual transfusion threshold used may vary from institution to institution, but evidence suggests that going below a haematocrit of 21% or haemoglobin of 7.0 g/dL may result in adverse outcomes and an increase in hospital mortality [9]. Therefore, it is obvious that a difference of only 1.0 g/dL in haemoglobin or a difference of only 3% in haematocrit could lead to a patient being transfused with banked red cells during or post bypass. Hopfer and co-workers [10] carried out an in vitro comparison of haematocrit using the I-STAT (conductivity) and the HemoCue (non blood gas photometry) analysers under simulated bypass conditions (crystalloid haemodilution) using the GenS (Coulter Counter) as the control. Photometry haematocrit results correlated exactly with the Coulter Counter, but conductometric results were lower by as much as 2.0 g/dL for haemoglobin and 4% for haematocrit. Steinfelder-Visscher and co-workers [11] carried out a prospective in vivo investigation during CPB in 88 patients over a sixmonth period. Haematocrit measurements were compared between the Gem Premier 3000 (conductivity) and the Sysmex 2100 (Coulter Counter). It was found that 37/55 samples that had haematocrit values below 20% using conductivity actually had haematocrit values above 20% when measured by the Sysmex. They concluded that when using conductivity, 67% of the 55 patients deemed below the transfusion threshold would have been unnecessarily transfused. Finally, in another prospective, randomised trial during CPB, Prichard and co-workers [12] evaluated haematocrit in 20 patients using the ABL 77 (conductivity), the ABL-720 (co-oximetry) and the Beckman LH 750 (Coulter Counter). The mean haematocrit using conductivity was 19.8 + 5.9%, while the mean calculated haematocrit using cooximetry was 24.1 + 5.6% and the mean haematocrit with the Coulter Counter was 23.8 + 5.6%. This is a respective inaccuracy in haematocrit values of 4.3% and 4.0% when using conductivity.

Table 1. Some POC conductivity and co-oximetry devices currently available on the market

counts. All are conditions created or present during cardiac surgery that carry over into the immediate postoperative period in the CVICU [1,2,3]. There are three elements that affect condumetric values, protein, temperature and electrolytes, all of which are altered during cardiopulmonary bypass (CPB).

protein changes during cpBDue to the increased volumes of crystalloids used during cardiac surgery, protein levels are routinely diluted during the course of bypass. Like red cells, protein molecules offer resistance to the passage of an electrical current through the solution. Hence, when the protein content of blood is diminished with crystalloids, conductivity haematocrit will increase and give a value that is falsely lower than the actual haematocrit of that sample [1].

The electrical resistance measurement of haematocrit using conductivity is dependent on the medium in which red cells are suspended (plasma). Osmotic increases in plasma (created by volume expanders) will influence the determination of haematocrit in the samples by giving falsely low haematocrit readings. This is due to intracellular/extracellular fluid shifting, which will temporarily cause red cells to shrink. Therefore, devices using conductivity to measure haematocrit will then interpret this as a lower haematocrit.

co-oximetrySeveral POC blood gas analysers [Table 1] and most laboratory blood gas analysers do not measure haematocrit, but utilise cooximeters to directly measure haemoglobin in the samples. The co-oximeter does this by using spectrophotometric analysis of blood samples to obtain four haemoglobin moieties: oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), carboxyhaemoglobin (COHb) and methaemoglobin (MetHb). Development of spectrophotometry dates back to the 1600s, and continued with Lambert in 1760 and Beer in 1852, but the first spectrophotometric measurements of blood did not take place until the 1930s [6]. A typical co-oximetry system consists of a light source, a series of lenses, several filters, mirrors that focus the light beams, a sample chamber, a temperature-regulated block, a haemolyser, a monochromator and photodiode detectors that emit electrons. By heating a blood sample to 37oC in a temperature-regulated box and allowing it to be haemolysed with high frequency vibrations, a translucent solution suitable for analysis is produced. Light from the lamp is then filtered and passes through the blood sample. The transmitted light is then focused through a grating that transmits the light into a spectrum. Specific wavelengths are then selected and directed onto photodiodes to produce electric currents proportional to the light intensities.

osmotic changes during cpBOther commonly used fluids during cardiac surgery are synthetic or blood derived volume expanders. The use of volume expanders during CPB influences plasma osmolality and subsequently create falsely low haematocrit readings when the POC device is using conductivity [1].

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9POC blood gas devices using conductivity to measure haematocrit are reliable in most clinical settings where there are no large variations in protein concentrations, no abnormally increased lipid profiles or white cell counts and no large use of volume expanders or osmotically active agents. Unfortunately, the latter are everyday occurrences in the cardiac surgery operating room. Another hazard of using blood gas analyser haematocrits as our transfusion trigger is that it may lead to inadvertent or premature red cell administration to our patients, and create concern about unnecessary medical/ legal issues. The evidence is clear: if we are going to offer the most accurate and consistently reliable diagnostic methods to determine transfusion triggers for cardiac surgery patients based on low haematocrit, the use of co-oximetry- derived haemoglobin is critical and should be the standard of care in cardiac surgery.autologous blood transfusions. Anesth Analg 1990; 71: 541-544. 3. McNulty SE, Torjman M, Wlodzimierz G et al. A comparison of four bedside methods of hemoglobin assessment during cardiac surgery. Anesth Analg 1995; 81: 1197-202. 4. Shapiro BA, Peruzzi WT. Clinical Application of Blood Gases (5th ed) CV Mosby; 1994; 334-36 5. RobertsV C. Hematocrit variations and electromagnetic flowmeter sensitivity. Biomed Engin 1969; 4(9): 408-12. 6. Tobin MJ. Principles and practice of intensive care monitoring. McGraw-Hill, New York 1998; 305-07 7. Reeves BC, Murphy GJ. Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery. Curr Opin Anaesthesiol 2008; 21(5): 669-73. 8. Scott BH, Seifert FC, Grimson R. Blood transfusion is associated with increased resource utilization, morbidity and mortality in cardiac surgery. Ann Card Anaesth 2008 11(1): 15-9. 9. Groom RC. High or low hematocrits during cardiopulmonary bypass for patients undergoing coronary artery bypass graft surgery? An evidenced based approach to the question. Perfusion 2002; 17(2): 99-10. 10. Hopfer SM, Nadeau FL, Sundra M et al. Effect of protein on hemoglobin and hematocrit assays with a conductivity based point of care testing device: comparison with optical methods. Ann Clin Lab Sci 2004; 34(1): 75-82.


11. Steinfelder-Visscher J, Weerwind PW, Teerenstra S et al. Reliability of point of care hematocrit, blood gas, electrolyte, lactate and glucose measurement during cardiopulmonary bypass. Perfusion 2006; 21: 33-7. 12. Prichard JS, French JS, Alvar N. Clinical evaluation of the ABL-77 for point of care analysis in the cardiovascular operating room. JECT 2006; 38: 128-33.

The authorGerard J Myers RRT, CCP Cardiovascular Perfusion Services QEII Health Sciences Center Halifax, Nova Scotia, Canada. Address Correspondence: Gerard J Myers RRT, CCP Manager, Cardiovascular Perfusion Services 5th Floor, Cardiac OR, NHI Campus QEII Health Sciences Center Halifax, Nova Scotia, Canada. B3K 6A3 Tel: +1 902 473-2198 email: [email protected]

references1. Stott RA, Hortin GL, Wilhite TR et al. Analytical artifacts in hematocrit measurements by whole blood chemistry analyzers. Clinical Chemistry 1995; 41: 306-11. 2. McMahon DJ, Carpenter, RL. Comparison of conductivity based hematocrit determinations with conventional laboratory methods in

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Wireless technology: enhancing information management in PoC testingtechnological advances have enabled certain diagnostic tests to be performed at the patients bedside, allowing time to be saved in the delivery of appropriate care. Additional developments in information technology have further enhanced Point-of-Care (PoC) testing by improving the documentation and sharing of results. this article describes how such advances have been applied to the PoC testing of blood glucose levels in hospitals.

by tiffany Page

sharing of information in hospitalsThe rapid evolution of information management and communication technology have revolutionised the way we record and share information in all walks of life from leisure to business, and not least in the provision of healthcare. Advances such as the electronic patient record, hospital information systems (HIS) and laboratory information management systems (LIMS), have made access to important, up-to-date patient information much quicker and easier, and have reduced the paper burden in healthcare facilities enormously. Key to the sharing of sensitive patient information has been the development of secure electronic communication options between systems, allowing information to be entered or viewed by authorised personnel from anywhere in a given healthcare facility. Such connectivity can be achieved, for example, by hard-wiring systems to a local area network (LAN), by connection to a personal computer via a USB port or by wireless transmission to the LAN (WLAN). These options facilitate the flow of information between professionals and have been adopted in hospitals worldwide to support patient care. They have become invaluable in the maintenance of accurate patient records. For example, in the UK their use has been encouraged to reduce potential errors and to improve staff compliance within the National Health Service [1]. The application of wireless communication in hospitals is a relatively new development, but its potential benefits, in terms of improved

Figure 1. The wireless hospital blood glucose meter, the Accu-Chek Inform II.

workflow and enhanced patient care, are being increasingly recognised. In the USA, more than 90% of medium and large hospitals either currently use wireless technology or have plans to adopt it in the future [2].

Taking technology to the patientWireless technology is associated with portability and improved mobility, since users are no longer confined by wires and cables to a particular stationary system or device. Mobile data collection, therefore, has enormous implications in hospitals where the use of POC technology is increasing. Advances in diagnostic technology have allowed certain tests to be performed accurately and reliably outside of the laboratory by equipment that can be situated closer to patient, either stationed at a convenient location on the ward or department, or even by portable equipment, allowing it to be carried to the patients bedside. Giving medical staff access to results at the earliest opportunity saves time in the delivery of appropriate, informed care, but the accurate recording and sharing of these results is essential. Often this is carried out manually, requiring the result to be written in the patients notes and/or entered into the electronic patient record at a near-by computer, thus presenting the risk of transcriptions errors or omissions of important information from the patient record [3]. There is a requirement, therefore, for technology that will help to reduce the opportunity for such errors.

Wireless technology may have an important role to play in meeting this need for POC diagnostics, allowing test results to be transmitted immediately to a centralised database, increasing the accuracy of the recorded information (by eliminating the possibility of transcription errors), enhancing data visibility and, ultimately, improving patient care.

poc blood glucose monitoringOne important biochemical investigation that is frequently performed at the patients bedside is the measurement of blood glucose. Whole blood can be analysed for glucose levels by a POC analyser, such as the cobas b221 Blood Gas Analyser, or by a handheld blood glucose meter, such as the Accu-Chek Performa and Accu-Chek Inform II Test Systems.

The growing problem of diabetesEven if the current prevalence of obesity remains stable, which seems unlikely, it is anticipated that the number of people with diabetes will more than double by 2030, as a consequence of population aging and urbanisation. The WHO estimates that, by 2030 there will be more than 360 million people in the world with diabetes. Good glycaemic control is important to reduce the risk of complications associated with diabetes, such a retinopathy, renal damage, cardiovascular disease and capillary damage.

11The number of blood glucose tests performed in hospitals is increasing, which could be attributed to reasons, including: The growing number of people with diabetes [see Box 1]. The number of people affected by diabetes is growing worldwide. The WHO estimates that, by 2030, there will be more than 360 million people in the world with diabetes [4]. In 2006, it was estimated that 2.4 million people in the UK alone had been diagnosed with diabetes and that as much as 10% of in-patient spending was used in the care of people with diabetes [5]. The use of Tight Glycaemic Control (TGC) protocols in the care of critically ill patients Blood glucose levels are also monitored in intensive care units (ICUs) where critically ill patients (with or without a history of diabetes) may experience a glucose imbalance caused, for example, by major organ failure or sepsis [3]. The implementation of TGC protocols, during the stabilisation of these patients, involves frequent blood glucose monitoring and intensive insulin therapy to maintain near normal blood glucose levels. Such measures have been shown to reduce the morbidity and mortality of critically ill patients [6] and to shorten the duration of stay in the ICU [7]. This increase in POC blood glucose testing has put pressure on hospitals to ensure that results are properly documented. Until recently, these results had to be recorded manually or transmitted to the HIS by returning the hand held blood glucose meter to a static docking station. Now, however, the worlds first wireless hospital blood glucose meter, the Accu-Chek Inform II Blood Glucose Monitoring System fromRoche Diagnostics [Figure 1], has recently been launched ion the market. This handheld device allows results and other important information (such as patient and operator details) to be transmitted wirelessly from the patients bedside. Not only does this improve the accuracy of documentation, but it also saves


Blood glucose measurement using a wireless hospital blood glucose meterThe worlds first wirelss hospital blood glucose meter, the AccuChek Inform II allows blood glucose testing to be performed at the patients bedside, improving the mobility of staff between patients. It is easy to use, with touch screen operation and simple on-screen instructions. Each test result is displayed on screen and stored automatically along with patient identification, operator identification, the time and date of the test, test strip lot data (entered manually or by scanning barcodes) and any relevant comments. Using the accurate and reliable Accu-Chek Performa Test Strips, the system only requires 0.6L of blood and provides results in just five seconds, reducing the wait time compared to other methods and thus improving workflow. The system will detect under-dosing, requiring adequate blood to be applied before a result is given, thus improving the accuracy of the method and enhancing patient safety. The versatile Performa Test Strips allow blood glucose levels to be determined in venous, capillary, arterial and neonatal (including cord) whole blood samples.



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PoINt oF CArE UPdAtEof POC coordinators by enhancing the audit trail and ensuring regulatory compliance. Since the system records and transfers operator details, the training and certification status of authorised users can be monitored to ensure that only trained personnel carry out blood glucose testing. This factor, combined with patient bedside validation, allows POC coordinators to track which members of staff are testing which patients and helps to improve patient care and safety by ensuring the right patient is receiving the right test at the right time.

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valuable time in the recording of results and provides immediate access to the information by authorised personnel.

enhanced connectivity optionsSince not every hospital has wireless capability, this system has a number of connectivity options in order to meet the individual requirements of professional healthcare providers. Connectivity can be achieved at the meters docking station, which can be free standing or wall mounted in a convenient location, via a USB cable or by hard-wiring directly to the Ethernet network. Alternatively, for facilities with a WiFi infrastructure, easy upgrading to provide wireless communication from the handheld meter (via an RF card) is possible. With this capability, the meter need only be returned to the docking station for recharging. The information that is transmitted to the HIS includes: test and control results operator and patient details consumable lot details configuration information additional user-entered comments As recommended by the Clinical and Laboratory Standards Institute, communication is bidirectional, which also allows firmware updates and additional information from the HIS to be sent remotely to all connected meters [8].

improving workflowStaff time is a major contributing factor to the cost of blood glucose tests [3] and so opportunities to improve workflow and save time for medical staff will also result in significant cost savings. The system saves time by allowing healthcare personnel to obtain an instant blood glucose result at the patients bedside. The wireless capability of the meter also saves time, and enhances regulatory compliance, by automatically recording and transferring results to the HIS. This gives medical staff more time to spend on the important task of caring for patients.

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references1. NHS Litigation Authority 2007. NHSLA Risk Management Standards for Acute Trusts 2. Roche Market Research 3. NHS Purchasing and Supply Agency 2008. Buyers Guide Blood Glucose Systems 4. WHO 2006. Diabetes, Fact Sheet No. 312, http:// www.who.int/mediacentre/factsheets/fs312/en/ 5. Department of Health National Diabetes Support Team 2007. Prescribing for diabetes in England. An analysis of volume, expenditure and trends. 6. Van den Bergh, G, Woutes P, Weeker F et al. Intensive insulin therapy in the critically ill patient. New Eng J Med 2001; 345: 1359-1367. 7. Van den Bergh G, Wilmer A, Hermans G et al. Intensive insulin therapy in the medical ICU. New Eng J Med 2006; 354: 449-461. 8. Clinical and Laboratory Standards Institute 2007. Point of Care connectivity; approved standard, POCT-A2, vol. 26, no. 23


flexible data managementThe Roche cobas IT 1000 software enables the information from the Accu-Chek Inform II to be captured and transferred seamlessly to the HIS. This powerful, browser-based data management tool can be used to handle information from a variety of POC devices (both Roche and non-Roche instruments), facilitating patient validation, operator recognition and material lot tracking. These information management capabilities help to enhance regulatory and facility documentation requirements for POC testing. The data management package allows stored information to be accessed by authorised personnel from any location in the hospital network, helping staff to better manage and treat patients clinical glucose needs. In addition, it improves the management and maintenance of POC equipment, allowing POC coordinators to obtain a summary of systems and their connectivity status at a glance from a remote location.

The authorTiffany Page Marketing manager Decentralised diagnostics Roche Diagnostics Basel, SwitzerlandMedica 2/A7 www.ihe-online.com & search 45097

enhancing quality controlThe Accu-Chek Inform II system can be configured to require in-range glucose control results before patient testing is allowed and to display a warning when control tests are required. Control test results and control solution details are also stored and transferred automatically to the HIS, meeting the needs


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Point-of-Care platelet function testingtransfusion of blood and blood products carries significant risk. Coagulation monitoring can guide component blood product therapy, and reduce transfusion. Antiplatelet therapy is commonplace in patients at risk of thrombosis and arterial occlusive disease. Platelet function monitoring can both assess adequacy of therapy and can quantify deficiency in platelet function during haemorrhage. inhibition is associated with haemorrhage. In the context of extra-corporeal circulation, platelet function can be adversely affected, compounding coagulopathy and risk of bleeding. Indiscriminate transfusion of blood and blood products, including platelets, is dangerous. A sensitive and specific test of platelet function will have far reaching implications; on the one hand it will enable clinicians to assess the adequacy of antiplatelet therapy and guide further therapy. On the other hand, accurate assessment of platelet contribution to haemostasis in situations of excessive haemorrhage/coagulopathy will facilitate rational and timely transfusion of appropriate component therapy. reflects reduced production or increased loss of platelets. In the presence of marked thrombocytopaenia and significant bleeding, platelet transfusion is indicated. Platelet count alone however is neither a specific nor sensitive indicator of the global contribution of platelets to primary haemostasis. Bleeding time is a clinical measurement, used to estimate platelet function, but it has major limitations due to operator and patient variability. Platelet aggregometry is the gold standard laboratory platelet function test. This is a time consuming test, and is subject to error due to, amongst other things, the need to make allowances in the amount of reagents required depending on absolute platelet count [1]. Newer tests of platelet function include flow cytometry, electron eicroscopy and enzyme-linked immunosorbent assays (ELISA).

by Prof. C. Harle

Why monitor platelet function?Platelets play an integral role in coagulation. They are involved in and affected by the inflammatory response, and there is a growing appreciation that manipulation of platelet function can modify and possibly prevent the sequelae of diseases associated with arteriolar thrombosis and occlusion. Excessive platelet aggregation is associated with thrombosis and tissue ischaemia (myocardial infarction/ stroke). Excessive platelet

Traditional platelet function testingPlatelet function requires adequate platelet numbers as well as an appropriate platelet response to the signals initiating and propagating platelet aggregation. Traditional laboratory based tests include the automated platelet count (Coulter). There is little consensus as to the minimum platelet count for adequacy of coagulation, as the context of bleeding is so variable. Thrombocytopaenia

surgery, platelet function and antiplatelet drugsCardiopulmonary bypass compromises platelet function, and is also frequently associated with the need for transfusion due to loss of platelet

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PoINt oF CArE UPdAtEantiplatelet activity, which would balance the risk of bleeding against that of thrombosis, and rationalise the administration of platelets to patients bleeding excessively during surgery. Not all patients respond in the same way to antiplatelet therapy. This may be in part due to drug-drug interactions such as that initially described between clopidogrel and atorvastatin [6], or antiplatelet resistance due to a variety of other proposed pharmaco-genetic reasons [7]. While controversy remains regarding the mechanisms for this resistance POC platelet function testing may be useful in identifying failure of antiplatelet therapy. This has huge implications given the already powerful evidence supporting the use of these agents to improve outcome in patients with CAD, cerebrovascular disease and other conditions where circulation is compromised due to vascular thrombosis.

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function as well as coagulopathy independent of platelet function. Patients who receive platelet transfusion following cardiac surgery have worse outcomes than those who do not, and while the need for platelet transfusion is likely to be greater in more ill patients, platelet transfusions per se are possibly directly responsible for bad outcomes [2]. The ability to monitor coagulation, including platelet function, at the point of care and adhering to treatment algorithms based on these monitors rather than traditional clinical judgment has been shown to reduce transfusion rates by guiding blood component therapy [3]. Platelet function monitoring to guide platelet transfusion could reduce unnecessary platelet transfusion, improving clinical outcomes, and reducing costs.

Management of coronary artery diseasesee us at Medica Hall16/E06There have been marked changes in the medical management of patients with coronary artery disease (CAD). In the early 1990s it was recognised that thienopyridine drugs such as clopidogrel are more effective than aspirin in preventing reocclusion of coronary arteries than aspirin following thrombolysis. Since then, there has been a dramatic increase in the rates of percutaneous coronary interventions (PCI). There have been improved outcomes for patients who have PCI and for other patients with CAD in recent years, in no small part due to the exponential increase in the prescribing of anti-platelet medications. Consequently many patients who require surgery are on aspirin and/or clopidogrel. These patients may have excessive perioperative bleeding due to platelet inhibition. This is particularly true for surgeries already at higher risk for bleeding like cardiac surgery. We have come to appreciate that cessation of these agents (as was commonplace prior to major elective cardiac and non-cardiac surgery) is associated with a significant risk of thrombotic complications in the perioperative period, including fatal myocardial infarction and stroke [4]. Abrupt cessation of antiplatelet therapy is thus undesirable. One of the proposed mechanisms of this phenomenon is a rebound hypercoagulability [5]. Platelet function monitoring could offer new insights into the effect of antiplatelet therapies, and identify rebound hypercoagulability. This might be a trigger to re-institute antiplatelet therapy before stroke or myocardial infarction occur. Platelet function monitoring could also be used to monitor the effect of specific antiplatelet therapies. As such it could act as guide in planning the timing of urgent surgery by identifying a therapeutic window of

pros and cons of poc testingPoint-of-Care (POC) testing empowers the clinician by increasing the understanding and applications of the test being carried out. POC testing infers ownership of the technology and engages clinicians in an aspect of care, which has become remote by virtue of the centralisation of many laboratory services. It also offers more immediacy than

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Coronary artery bypass grafting: the ability to monitor coagulation/platelet function at the pointof-care and adhering to treatment algorithms based on the monitors instead of traditional clinical judgment has been shown to reduce rates of platelet transfusion.

15the sendingof tests to a laboratory does, avoids some of the delays associated with transfer of specimens and reduces communication breakdown with laboratory personnel. It is as close to real time testing as we can get. Automation and networked computerisation have to a large extent overcome many of the issues that historically drove clinical side room testing into technology to contemporaneously mimic all of the pharmacological, pathological and physiological conditions that affect platelet function. Thrombelastography (TEG) is in itself old technology, which offers graphical representation of global coagulation by measuring the visco-elastic properties of evolving thrombus in whole blood activated by either Kaolin or other activators, in vitro. It provides information about fibrin deposition as well as the relative contribution of platelets to primary haemostasis. An important recent development for TEG is the development of Platelet Mapping technology which allows estimation of the percentage inhibition of platelet function by aspirin and or clopidogrel. The Platelet Function Analyser (PFA 100) is a POC platelet function monitor that estimates platelet aggregation in conditions


mimicking physiological platelet aggregation. The instrument operates by measuring the time it takes for flow to cease when blood is aspirated through an aperture in a nitrocellulose membrane measuring the time it takes for aggregation induced by collagen, epinephrine, ADP or combinations thereof on the membrane to stop flow. The Rapid Platelet Function Assay (RPFA), (Formerly marketed as Ultegra) is a whole blood

Coagulation monitoring can guide component blood product therapy, and reduce transfusion.the laboratory. Calibration and maintenance of machines and equipment is much easier, and results can be stored centrally within hospital data storage facilities and be directly linked to electronic patient records. Nevertheless most clinicians are not specifically trained in many aspects of quality assurance and equipment maintenance, let alone the biomedical engineering aspects of sensitive equipment. Much of this equipment requires time to calibrate, maintain and operate. Ideally, these tasks should not be performed by the physician but by support personnel, adding to their onerous workload in the clinical environment. Similarly, a partnership between core laboratory services, biomedical engineering services, clinicians and support staff from both the laboratory and the clinical area should exist to run POC tests, engaging the support and expertise of core laboratory and pathology services. Those using POC testing devices need to understand the tests and be able to interpret the results.

poc platelet function monitorsSeveral devices are currently marketed and more are in development. Each of these devices has merits and shortcomings. Most of the latter can be ascribed to the inability of currentwww.ihe-online.com & search 45045


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PoINt oF CArE UPdAtE3. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999; 88: 312-9. 4. Newsome LT, Weller RS, Gerancher JC, Kutcher MA, Royster RL. Coronary artery stents: II. Perioperative considerations and management. Anesth Analg 2008; 107: 570-90. 5. Serebruany VL, Midei MG, Meilman H, Malinin AI, Lowry DR. Rebound platelet activation after termination of prasugrel and aspirin therapy due to confirmed non-compliance in patient enrolled in the JUMBO Trial. Int J Clin Pract 2006; 60: 863-6. 6. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003; 107: 32-7. 7. Ferguson AD, Dokainish H, Lakkis N. Aspirin and clopidogrel response variability: review of the published literature. Tex Heart Inst J 2008; 35: 313-20.

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aggregometry assay. It measures light absorbance through a chamber, containing lyophilised membrane protein iso-TRAP or ADP and tiny fibrinogen coated beads. When blood is added to the chamber, platelets are activated by the iso-TRAP or ADP, and interact with the beads changing the light absorbance. Platelet Works compares platelet counts in whole blood before and after aggregation induced by collagen or ADP, and correlates very well with standard aggregometry. Impact Cone and Plate(let) Analyser (CPA) is a device in which whole blood is subjected to shear forces in a spinning cone, and platelet adhesion to the cone is analysed. It has the theoretical advantage of being able to reproduce physiologically relevant shear conditions as well as being able to monitor aspirin and clopidogrel therapy.


conclusionThe evidence to support platelet function testing to guide both antiplatelet therapy as well as blood transfusion is growing. In the authors opinion the growth in the technology to measure platelet function will increase our understanding of platelet function, coagulopathy and antiplatelet therapy. POC application of this technology is likely to make a dramatic and favourable impact on patient care and outcomes.

The authorDr Christopher Harle Assistant Professor Site Chief University Hospital, Department of Anesthesia and Perioperative Medicine London Health Sciences Centre 339 Windermere Road London, Ontario N6A 4GT, Canada Tel +1 519 663 3031 Tel +1 519 685 8500 Extension 34720 e-mail [email protected]

FAZZINI s.r.l. s.s. Padana Superiore 317 20090 Vimodrone (MI) - ITALY Tel. ++39/02265152-1 Fax ++39/0227409242 e. mail: fazzini @ fazzini.it www.fazzini.it

references1. Pamukcu B. A review of aspirin resistance; definition, possible mechanisms, detection with platelet function tests, and its clinical outcomes. J Thromb Thrombolysis 2007; 23: 213-22 2. Spiess BD, Royston D, Levy JH, et al. Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes. Transfusion 2004; 44: 1143-8.

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dual source cT imagingEdited by P. R. Seidensticker and L. K. Hofmann Published by Springer (2008), 303pp, e5.30

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The introduction of Dual Source Computed Tomography (DSCT) in 2005 was an evolutionary leap in the field of CT imaging. Two X-ray sources operated simultaneously enable heart-rate independent temporal resolution and routine spiral dual energy imaging. The precise delivery of contrast media is a critical part of the contrast-enhanced CT procedure. This book provides an introduction to DSCT technology and to the basics of contrast media

administration followed by 25 in-depth clinical scan and contrast media injection protocols. All were developed in consensus by selected physicians on the Dual Source CT Expert Panel. Each protocol is complemented by individual considerations, tricks and pitfalls, and by clinical examples from several of the worlds best radiologists and cardiologists. This extensive CME-accredited manual is intended to help readers to achieve consistently high image quality, optimal patient care and a solid starting point for the development of their own unique protocols.

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NEWs IN BrIEFeven mild sleep apnea increases cardiovascular risk

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People with even minimally symptomatic obstructive sleep apneas OSA, i.e. the apnea caused by obstruction of the airways and characterised by pauses in breathing during sleep, may be at increased risk for cardiovascular disease because of impaired endothelial function and increased arterial stiffness, according to a study led by Dr Kohler at the Oxford Centre for Respiratory Medicine in the UK. Results of the study have been published in a recent issue of the American Journal of Respiratory and Critical Care Medicine. The controlled, cross-sectional study was performed to assess differences in endothelial function (often a harbinger of cardiovascular problems to come), arterial stiffness and blood pressure in patients with minimally symptomatic OSA. The researchers compared 64 patients who had proven OSA to matched

control subjects without OSA. Their findings suggested that minimally symptomatic OSA is a cardiovascular risk factor to a degree not previously known. The augmentation index, a measure of central arterial stiffness that independently predicts cardiovascular events in high-risk populations, was significantly higher in patients with minimally symptomatic OSA compared to matched controls. Endothelial function, as indicated by decreased vascular reactivity of the arteries, was also impaired compared to control subjects without OSA. The difference in arterial stiffness between OSA patients and control subjects was comparable to the effect seen after four weeks continuous positive airway pressure (CPAP) therapy in patients with moderate to severe symptomatic OSA. This suggests that asymptomatic or minimally symptomatic patients with OSA may enjoy a cardiovascular benefit from CPAP therapy. Dr Kohler and colleagues are currently investigating the effects of six months CPAP therapy on arterial stiffness and endothelial function as part of an international randomised controlled trial (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular Trial; MOSAIC) which will show the impact of CPAP therapy on cardiovascular risk in patients with minimally symptomatic OSA.http://www.thoracic.org/sections/publications/ press-releases/resources/110108kohler.pdf

post-cardiac arrest care key to survival

The urgent need for treatment doesnt end when a person regains a pulse after suffering sudden cardiac arrest; healthcare providers need to move quickly into post-cardiac arrest care to keep a person alive and ensure the best outcome. Brain injury, heart dysfunction, systemic inflammation and the underlying disease that caused the cardiac arrest all contribute to the high death rate in resuscitated patients. Collectively, these symptoms are known as post-cardiac arrest syndrome. The largest modern report on cardiac arrest resuscitation was published by the USA National Registry of CPR in 2006. Among the 19,819 adults and 524 children whose hearts were re-started, in-hospital mortality rates were 67 percent and 55 percent, respectively. A new statement says there is growing evidence that appropriate post-cardiac arrest care can lower the death rate and improve functional outcome

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NEWs IN BrIEFschedule of clinic visits. However, the filtration ability of the peritoneum can lose efficiency over time, requiring patients to discontinue PD. In order to understand this change in the peritoneum, a Spanish research team examined the dialysis fluid from PD patients, and identified molecular signals that cause abnormal changes in the peritoneum. The researchers also found that pharmacologically disrupting these signals allowed the abnormal cells to revert back to their original state. The effectiveness of PD could be maintained, and even former PD patients might be able to resume PD rather than continue with traditional hemodialysis.http://dmm.biologists.org/

for these patients. Research shows that many aspects of post cardiac arrest syndrome can be treated. Unconscious adult patients resuscitated after out-of-hospital cardiac arrest were recommended to receive mild therapeutic hypothermia (cooling to 32C - 34C for at least 12 to 24 hours), which can improve survival and decrease the risk of brain damage. Patients resuscitated from a cardiac arrest caused by a heart attack (as seen on an electrocardiogram, or ECG) should have immediate coronary angiography (an X-ray examination of the heart arteries) to check for artery blockages. Standard guidelines for heart attack treatment should be followed, which may include an artery-opening procedure (angioplasty) or administering a clot-busting drug to re-establish blood flow to the heart. Treatment for high blood sugar, seizures and infection, all of which are common concerns after cardiac arrest resuscitation, were also discussed. Inserting an implantable cardioverter defibrillator (ICD) is indicated for many patients with good neurological functionhttp://circ.ahajournals.org/cgi/reprint/ circUlaTionaha.108.190652

according to a new study published online in the Oxford University Presss journal Human Reproduction on behalf of the European Society of Human Reproduction and Embryology. The study which is among the first to examine depression and preterm delivery in a representative and diverse population in the United States -- looked at 791 pregnant members of the US-based health care organisation, Kaiser Permanente, in San Francisco city and county from October 1996 through October 1998. Researchers interviewed the women around their 10th week of pregnancy and found that 41 percent of the women reported significant or severe depressive symptoms. The women with less severe depressive symptoms had a 60 percent higher risk of preterm delivery defined as delivery at less than 37 completed weeks of gestation compared with women without significant depressive symptoms, and the women with severe depressive symptoms had more than twice the risk. Depression during early pregnancy may interfere with the neuroendocrine pathways and subsequently placental function.http://humrep.oxfordjournals.org/content/vol23/ issue10/index.dtl

old blood linked to infection

depression during pregnancy can double risk of preterm deliveryDepressed pregnant women have twice the risk of preterm delivery compared with pregnant women with no symptoms of depression,

Modification of cellular changes in peritoneum prolongs pdOne of the most devastating aspects of kidney failure is the strict, time-consuming treatment regimen. Patients with diseased kidneys traditionally need to attend a dialysis clinic three times per week, with each session lasting three to five hours. An alternative to this treatment involves the creation of an artificial kidney in the well established process known as peritoneal dialysis (PD). In this, fluid is inserted into the abdominal cavity, and the blood vesselrich peritoneum acts as a filter for the blood. Exchanges of dialysis fluid can take place at home, thus freeing patients from a rigid


Blood stored for 29 days or more, i.e. nearly two weeks less than the current standard for blood storage, is associated with a higher infection rate in patients who received transfusions with the blood. In a new study, researchers found that patients who received transfusions with blood stored for 29 days or more were twice as likely to suffer from nosocomial infections, including pneumonia, upper respiratory infections and sepsis, with the oldest blood being associated with the most infections. Current regulations allow red blood cells to be stored up to 42 days, after which they must be discarded. Researchers from Cooper University Hospital, USA, examined the association between the age of packed red blood cells and the development of nosocomial infections (NOSO) in 422 patients receiving blood transfusions who were admitted to an ICU from July 2003 to September 2006. The analysis showed that 11 percent of patients died, while 57 patients (13.5 percent) developed NOSO. Patients who developed NOSO had received at least one unit of blood with a significantly higher age (28.5 days vs. 32 days), and had received a significantly greater number of units of blood. Patients who received transfusions with blood that was 29 days or older were twice as likely to develop

NEWs IN BrIEFNOSO as those receiving transfusions with blood stored for 28 days or less.http://www.chestnet.org/about/ press/releases/2008/chesT/pdf/ Bloodstorage.pdf

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gene scan of alzheimers families identifies four new suspect genes

marker is in a gene that produces a synaptic protein. The team is continuing to investigate the implications of these novel genes as well as the possible impact of less strongly associated genes also identified in this study.http://esciencenews.com/articles/2008 /10/30/gene.scan.alzheimers.families. identifies.four.new.suspect.genes

potential protein targets for malaria vaccineA large number of parasite proteins that may prove useful in the

development of a human malaria vaccine have been characterised. Despite many years of effort, a vaccine is still not available to fight the deadly disease. A promising method for vaccination is to weaken the parasites that initially invade liver cells and stimulate an immune response so that they dont develop further. This can be achieved by genetically inactivating individual parasite genes that are active during the parasites growth in the liver. A group of Dutch researchers

from Nijmegen University identified certain proteins essential for sporozoite development in humans and thus likely to be valuable targets of a vaccine.http://www.plospathogens.org/article/ info%3adoi%2f10.1371%2fjournal. ppat.1000195

The first family-based genomewide association study in Alzheimers disease has identified the sites of four novel genes that may significantly influence risk for the most common late-onset form of the disorder. The study presents the first results of the Alzheimers Genome Project supported by the Cure Alzheimers Fund and the US National Institute of Mental Health. In the first stage of their investigation, the researchers in the project tested around half a million DNA markers, covering most of the human genome, in a National Institutes of Mental Health (NIMH) sample of more than 400 families in which at least three members were Alzheimers patients. That analysis found five markers exhibiting genetic association with Alzheimers, one of which corresponds to the gene for apoE, the only gene firmly established to increase risk for lateonset Alzheimers. To confirm the four novel sites, the researchers analysed samples from over 900 additional families. The strongest marker was located on chromosome 14 and was further supported by an independent analysis comparing 1,400 Alzheimers patients with healthy controls. Another of the identified markers is in a gene known to cause spinocerebellar ataxia, a movement disorder that involves the death of nerve cells in other parts of the central nervous system, and a third is in a gene involved with the innate immune system, part of the bodys defence against bacteria and viruses. The fourthwww.ihe-online.com & search 44801

Imaging potential hampered by shortage of medical isotopesWith the dramatic progress in engineering and software over the last several decades the progression of medical imaging capabilities has been nothing short of spectacular. The evolution has carried us far from what was, (and still is), provided by X-rays, CT scans and MRI, namely purely structural and anatomical analysis of a suspect tissue or organ. Thus, currently one of the most exciting prospects in the medical imaging field is that, at long last, clinicians will be able to reap the benefits of the combination of such detailed structural, functional and molecular information. This can be used not only for the mere diagnosis of the patient or even monitoring the progress of therapy but also for the Holy Grail of medicine, namely personalised and thus optimised medicine, or even the cost-effective screening of at-risk individuals and timely prophylactic therapy. Of course no one technique is capable of yielding such a treasure trove of data. It is in fact the combination of various techniques, each contributing their own particular information that will provide the vital synergy. The field of hybrid imaging is no mere futuristic dream but already exists in practice. Today for example no PET scanner exists as a stand-alone instrument whereas PET/ CT and SPECT/CT are relatively common. It has been estimated that PET/CT data are actively used in diagnosis or treatment monitoring of nearly a third of all oncology patients. PET/CT and SPECT/CT are of course techniques based on the injection of radionuclide markers and as such are part of the wider field of nuclear medicine. Unfortunately right now what is preoccupying the field is less the dizzy potential of future technological innovations but a much, much more mundane topic, namely the current lack of easy availability of isotopes for medical use. This has been triggered by unexpected shutdowns at the relatively few nuclear reactors throughout the world that produce isotopes for imaging (and also therapeutic purposes). Some of the shutdowns, e.g. those of the BR2 reactor in Belgium and the Osiris reactor in Saclay, France were pre-planned as part of routine maintenance programmes necessary to keep the largely ageing reactors safe and efficient. Other shut-downs were however anything but planned. For example the high flux research reactor (HFR) facility at Petten in the Netherlands, which is run on behalf of the European Unions Joint research centre, went down unexpectedly due to a fractured pipeline. Ever since safety issues were discovered at the Chalk River reactor in Canada last year, the operators of the other reactors have been extremely attentive to any signs of problems with theirs. Thus when gas bubbles were unexpectedly discovered in coolant pipes at the Dutch reactor during routine maintenance procedures, the operators had literally no alternative but to close the whole plant down. Worse, the difficulty of access to the pipes means that repairs will not be complete until well into next spring. Personnel at the few remaining reactors that are still operating, in particular the South African and Canadian reactors, are making valiant efforts to try and make up for the shortfall caused by the Dutch problem, but since the Dutch reactor is the source of 30-40% of the worlds medical isotopes, it is inevitable that shortages will occur. The situation is exacerbated by the fact that the half-life of the isotopes used is extremely short, so hospitals cannot hold any stocks of the isotopes but instead must rely on regular deliveries. In a strangely unfortunate co-incidence, the second Belgian isotope-producing reactor in Fleurus, Belgium at the same time also suffered an unexpected accident, this time even resulting in a leakage of low-level radiation into the surrounding countryside, and of course necessitating an additional shut-down period while the problem is investigated and repaired. It has been know for a long time that the small number of isotope producing reactors throughout the world means that any production interruptions such as the current combination of planned maintenance shut-downs and unexpected breakdowns can tip the production schedule into severe shortages. The authorities have however been reluctant to encourage any construction of new reactors because of the vague fear that they could in some way or another just represent more sources for terrorists to get hold of material that could form the basis of a dirty radioactive bomb. In a slightly perverse way it can be sometimes useful to come down to earth from the heady predictions of the potential wonders of future imaging technology and their benefits to patients to the hard reality that a lot is dependent on apparently mundane aspects such as the in-time delivery of material. It is too bad that these mundane aspects are currently actually having a direct effect on patients well-being. Despite the current production problems, however, the field remains resolutely optimist. The mouth-watering menu of forward-looking presentations scheduled at the upcoming RSNA congress testifies to this.

November 2008

Medical imaging SpecialWhat does the future hold for MRI? Page 22 - 25 Handbook of cardiovascular CT Page 25 Tumour imaging with radiolabelled non-natural amino acids Page 26 - 29 A selection of the latest products in the medical imaging field Page 30 - 34 RSNA Preview Page 35

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Issue N6 November 2008

22

MedICAl IMAgINg SPeCIAl

What does the future hold for MRI?Magnetic resonance imaging (MRI) is already the most flexible diagnostic imaging modality, allowing us to characterise many aspects of the living patient from metabolism and physiology to tissue microstucture. Here we consider the future directions for MRI technology and predict that even after 30 years of continuing developments there are still further major advances which can be made in diagnostic MRI. into increased sensitivity (double at 3T vs. 1.5T), which can be used to obtain higher resolution images or traded for speed (shorter examination time). Interestingly, the duration of a typical MRI patient investigation has not declined significantly in the last few years, with faster image acquisition simply allowing a wider range of image types to be collected in the individual. Neurological exams at 3T can easily achieve better than 0.4mm in-plane resolution in short scan times [Figure 1]. Currently, body applications of 3T are more variable in their reproducibility (e.g. cardiac methods) and, while 1.5T remains the current standard, developments in scanner technology will eventually realise the benefit of 3T in these clinical areas too. Although many ultra high-field (7T and above) brain imaging systems are in research use, these are unlikely to have any major impact as a clinical technology in their own right, but as with all cutting edge developments, innovations made at 7T will trickle down and affect routine clinical products. At the other extreme of field strength however, hardware is being developed using a technique known as pre-polarised MR, which can achieve 1.5T image quality in peripheral limbs using only a 0.1T magnet, and provide artefact-free images in the presence of metallic implants all in a prototype scanner costing around $50,000 [3]. For specialist clinics, the commercial versions of such technology will offer a package of high quality images, patient convenience and affordability. Another area of hardware development that continues to develop is receiver coil technology. All modern scanners have multiple receiver channels a development which began in 1990 with the introduction of phased-array spine coils and this area moves onward almost unabated. Small receiver coils have high local sensitivity but limited field of view (FOV). Combining a number of such small coils into a single device the multi-channel coil restores full FOV while maintaining sensitivity. Eight and 16 channel devices are increasingly common and systems have been designed for modular upgrade to 24, 32 channels and beyond. Research systems show benefits of at least 32 channels in brain imaging [4], and up to 100 channel devices have been designed [5], but the sheer complexity of such systems means that they are less likely to be clinically relevant.

by Prof. Andrew Blamire

Predicting the future developments in any major technology is always a challenge, and MRI is no exception. In the early days of MRI predictions were made that imaging would not be possible above a field strength of 0.23T [1], and that the process by which body sections are imaged (slice section) even violated a fundamental principle of physics, namely the Uncertainty Principle, [2]. Fortunately for clinical radiology, such gloomy predictions were not realised and virtually every district hospital in Europe now operates scanners based on high field magnets. Nowadays there is a wealth of worldwide research underpinning the future commercial developments of diagnostic technologies. The future path for MRI can be predicted by identifying the most promising research findings, which over time (typically five to 10 years) and with adoption by scanner manufacturers, will arrive in the clinic - the MRI of the future therefore depends on MRI research today. So what might we expect from MRI in the coming decade?

Integrated modalitiesIntegrated modality scanners are a particularly exciting engineering development that will impact on patient assessment, particularly in specialist oncology centres. Positron emission tomography (PET) is indicated for diagnosis in cancer but provides no structural data. PET systems are already integrated with CT systems to provide anatomical detail, but still suffer from poor soft tissue contrast. Patients therefore may undergo separate MRI investigation to collect the soft tissue information. Integrating PET with MRI into a single modality is therefore a prime technological goal. Both rodent and human realisation of combined (simultaneous) PET-MRI scanners have been reported in the last few years, overcoming the challenge of operating the PET detector system within the hostile environment of a high magnetic field [6].

MR scanner hardwareIn the mid-1990s research institutions began ordering high-field scanners operating above the common 1.5 Tesla (T) clinical limit. This was motivated by the basic physics of scanning, which states that signal strength (and hence image quality) increases directly with magnetic field strength. As a result, high field strength MRI (3T) scanners have been available as clinical products for more than five years and are gradually being established as the routine field strength, a trend which is firmly set to continue and is likely to see most hospitals working at 3T in the next decade. Compact scanner design allows the new generation 3T systems to slot into old 1.5T scanner sites. Field strength for neurological examinations translates directly

Figure 1. Neurological exams at 3T can easily achieve better than 0.4mm in-plane resolution in short scan times. The above figure shows clinical 3T neuro scans. Left: T2w. TSE sequence, 0.3mm resolution, 5.2mins Right: Non-contrast TOF angiogram, 0.25mm resolution, 8 mins

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MedICAl IMAgINg SPeCIAlbrain [Figure 2], providing data on metabolic, physiological, micro- and macrostructural tissue integrity, and these may well become the norm. These fundamental biological parameters are inter-related and the relationship between them is likely to provide additional detail on tissue injury or disease. Advanced image processing techniques are currently being developed that will provide the radiologist with tools to assimilate the many types of data.

New contrast agentsAs clinical treatment of many conditions become increasingly personalised, improved diagnosis, and hence specific selection of therapeutic treatments based on knowledge of disease phenotype, will become important. For many years PET has offered the ability to map molecular pathways, receptor density, etc, via appropriate radioligands, but PET cannot provide the level of spatial resolution offered by MRI, and is limited in availability. MRI is responding to this challenge through the development of targeted MR contrast media that bind to specific molecular or cellular targets. This work is currently in its infancy, but recent data in animal models have shown the power to detect the earliest phase of brain injury [9]. Although the transfer of such technology into useful clinical compounds requires extensive development and product licensing, these data show clear potential for this technique.

Figure 2. Integrated examination protocols collecting fully quantitative measures are already possible in the brain, providing data on metabolic, physiological, micro- and macro-structural tissue integrity. The above figure shows an integrated quantitative 3T neuro exam Top left : T1w relaxation map. Top right T2 relaxation map Bottom (from left to right) : Mean diffusion, Diffusion Anisotropy, cerebral blood flow, CBF

Once fully commercialised, this technology will improve data quality, allow more accurate rendering of metabolic to structural data and improve patient throughput, as PET and MRI can then be collected simultaneously in the same scan session.

Scanning sequencesMRI is different from all other diagnostic modalities in that the hardware configuration plays little role in the image contrasts that can be collected, these instead being dictated by software through the scanning sequences. Several new methods show potential. Perfusion measurements have become central to many neurological protocols (particularly in acute stroke), based around kinetic tracking of a bolus contrast agent injection. For the past 10 years alternative non-contrast agent approaches have been developing, known collectively as arterial spin labelling (ASL), and at 3T these sequences show real promise of providing clinically useful images of cerebral blood flow CBF [Figure 2, bottom right]. Image contrast generated by any MRI sequence relies (partly) upon the rate at which the transient MR signal is decaying away (the relaxation time T2) the time at which the signal is recorded (the echo time,

TE). Recently clinical research findings have been published using ultra-short echo time (UTE) sequences where TE has been reduced from its typical range of 1-10 milliseconds down to 10-50 microseconds [7]. This has created a whole new set of image contrasts allowing direct imaging of tissues which have traditionally not been seen by MRI (e.g. ligaments and tendons, [8]).

ConclusionsMRI has continued to rapidly develop since its introduction as a clinical tool in the early 1980s. Widespread use of 3T scanners is already becoming a reality and future developments in coil technology and new image contrasts will continue to provide new tools for clinical diagnosis. Combined modalities and targeted contrast media are further on the clinical horizon, but will become a reality for specialist referral centres in the coming years.

Integrated modality scanners are a particularly exciting engineering development which will impact on patient assessment particularly in specialist oncology centres.While conventional T1 and T2 weighted scans will always remain the bed-rock of the clinical examination, it is clear that truly quantitative scan types will be needed as we enter the era of personalised medicine, where noninvasive monitoring of treatment response will be increasingly important. Integrated examination protocols collecting fully quantitative measures are already possible in the

References1. Hoult DI, Lauterbur PC. Sensitivity of the Zeugmatographic Experiment Involving Human Samples. Journal of Magnetic Resonance 1979; 34: 425-433. 2. Hoult DI. Zeugmatography - Criticism of Concept of a Selective Pulse in Presence of a Field Gradient. Journal of Magnetic Resonance 1977; 26: 165-167. 3. Venook RD et al. Prepolarized magnetic resonance imaging around metal orthopedic implants. Magnetic Resonance in Medicine 2006; 56: 177-186. 4. Wiggins GC et al. 32-Channel 3 tesla receive-only phased-array head coil with soccer-ball element geometry. Magnetic Resonance in Medicine 2006; 56: 216-223.

25Book RevIeW


Handbook of Cardiovascular CTEssentials for Clinical PracticeEdited by Matthew J. Budoff and Jerold S. Shinbane Published by Springer 2008, pp 260, e46.95

Cardiovascular CT has evolved from novel technology to research tool to essential clinical imaging modality at an astounding pace. The technology has great relevance for many medical and surgical disciplines focused on the treatment of cardiovascular disease. Thanks to the ability of CT to image anatomical, physiological and tissue characteristics of large and small vessel within seconds, and reconstruct multimodal two- and three-dimensional images within minutes, cardiovascular CT has facilitated practical clinical applications important to cardiovascular diagnosis, risk stratification and procedure guidance.

This book is a primer to assist cardiologists, radiologists and other readers involved in cardiac imaging. The new wave in CT technology requires education and training focused on providing an understanding of the essentials of methodology, technique, and clinical image analysis. Reviewing the practical techniques and interpretation of the modality, the compact format provides a handy reference tool and provides the answers to important cardiovascular CT questions. Concise chapters are geared towards covering the essential topics, but with additional depth provided by the inclusion of teaching pearls as well as selected key images.

Springer VerlagHeidelberg, germanywww.ihe-online.com & search 45073

5. Wiggins GC et al. A 96-channel MRI system with 23- and 90-channel phase array head coils at 1.5 Tesla. Proceedings of the 13th Scientific Meeting of the International Society for Magnetic Resonance in Medicine. 2005. Miami, Florida, USA. 6. Schlemmer HPW et al. Simultaneous MR/PET imaging of the human brain: Feasibility study. Radiology 2008; 248: 1028-1035. 7. Gatehouse PD, Bydder GM. Magnetic resonance imaging of short T-2 components in tissue. Clinical Radiology 2003; 58: 1-19. 8. Robson MD, Bydder GM. Clinical ultrashort echo time imaging of bone and other connective tissues. NMR in Biomedicine 2006; 19: 765-780. 9. McAteer MA et al. In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nature Medicine 2007; 13: 1253-1257. 10. Blamire AM. The technology of MRI - the next 10 years? British Journal of Radiology 2008; 81: 601-617.

The authorFor a more in-depth discussion about future MRI developments, the reader is directed to the recent review by the same author [10]. Andrew M. Blamire, B.Sc., Ph.D. Professor of MR Physics, Newcastle University, Newcastle upon Tyne, United Kingdom. [email protected]

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MedICAl IMAgINg SPeCIAl

Tumour imaging with radiolabelled non-natural amino acidsRadiolabelled non-natural amino acids are an important class of tumour imaging agents for positron emission tomography (PeT) and single photon emission computed tomography (SPeCT). The best established use of these agents is for the evaluation of brain tumours, and there is also emerging data supporting their use for selected tumours outside the brain. This article provides an overview of this class of tumour imaging agents. as LAT1 of the system L family are associated with worse prognosis in a variety of tumours including breast cancer and gliomas [3,4]. Thus, radiolabelled amino acids could provide a means for biological characterisation of tumours beyond simple lesion detection. Some naturally occurring amino acids, in particular L-[11C]methionine (MET), are effective tumour imaging agents [5]. However, non-natural amino acids have certain advantages over natural amino acids for tumour imaging. Naturally-occurring amino acids can be labelled with carbon-11 for PET, but the short half-life (t1/2 = 20 minutes) places significant constraints on production and distribution. In contrast, nonnatural amino acids can be labelled with longer lived radionuclides such as fluorine-18 (t1/2 = 110 min) for PET and iodine-123 (t1/2 = 12.3 hours) for SPECT. Unlike most natural amino acids, many of the non-natural amino acids are metabolically stable, which can simplify image interpretation and kinetic analysis. Non-natural amino acids are a structurally diverse class of compounds that can be optimised in terms of transport selectivity and imaging properties for a particular application. of phenylalanine and tyrosine such as 3-[123I] iodo-a-methyl L-tyrosine (IMT), O-(2-[18F] fluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-L-[18F]fluorophenylalanine (FDOPA) have been most extensively evaluated in humans [6-10]. These radiotracers typically provide better tumour visualisation than [18F] FDG and can provide additional diagnostic information not available with magnetic resonance imaging (MRI) alone. One of the important advantages of radiolabelled amino acids compared to [18F]FDG is their relatively low levels of uptake in the normal brain. Studies in human patients with brain tumours using [123I]IMT, [18F]FET and [18F]FDOPA typically demonstrate peak tumour uptake of tracer at approximately 15 to 20 minutes post injection, with tumour to normal brain ratios in the order of 2:1 to 3:1. To a first approximation, these tracers and [11C]MET have similar imaging properties for brain tumours with uptake in viable tumour including areas that do not have contrast enhancement on MRI, providing a more accurate assessme

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