2 M O N D AY @ M E D I C A An asset to improve cancer management Liquid biopsy has enormous potential Report: Mark Nicholls It is non-invasive, delivers a chance of early diagnosis, prognostic infor- mation and sequential monitoring, and, believes Professor Francesco Salvatore, the enormous poten- tial of liquid biopsies has still to be reached. However, the positive results obtained so far have ‘opened the door to a promising new multi- faceted group of tumour markers, at present collectively designated “liq- uid biopsy”,’ he explained. While liquid biopsy is a relatively new term, Salvatore suggested the real essence of its meaning is much older in laboratory medicine: haemo- chromocytometric analysis to search for altered blood cells was one of the first tests used in medical diagnostics and thus can be considered the first real liquid biopsy. (DNA and RNA) in terms of their quali-quantitative analyses, the diag- nostic performance of oncohaema- tological tests became more sensi- tive. Today, femtomole amounts of specific nucleic acid sequences are routinely used in leukaemia and lym- phoma patients. In 1997, Salvatore’s group was among the first to produce evidence of the presence of RNA sequences in the blood of patients with solid tumours. Soon after, the molecular analysis of nucleic acids was inte- grated into pathology practice. The concept of liquid biopsy is evolving, he said, with clinical trials under way with various technologies – such as next generation sequenc- ing of nucleic acids and other high productivity ‘omics, analyses – to try to reach high diagnostic sensitivity in body fluids. With the test later extended to molecular aspects of nucleic acids With cellular and molecular mark- ers that can be visualised, analysed MEDICA 12.–15. November 2018 Düsseldorf Hall 16, Stand No. E58 Quality & Innovations ADVANCED MEDICAL SOLUTIONS Ԃ BIOMAG Ԃ BRNO UNIVERSITY OF TECHNOLOGY Ԃ COMPEX / JETT MEDICAL Ԃ GLOBAL BIOMEDICA Ԃ KETTEX DEVELOPMENT Ԃ MEDIN Ԃ SPECIÁLNÍ MEDICÍNSKÁ TECHNOLOGIE Ԃ SYNTHESIA Ԃ VUP MEDICAL Ԃ WATEK Ԃ ZDRAVOPRO Ԃ affected tissue or organ.’ One of the benefits of liquid biopsy, he added, is the ability to identify tumour-associated cells and molecules within body fluids, primar- ily blood, at the earliest opportunity – leading to better prognosis. ‘Obviously, this procedure must be accompanied by highly sensi- tive methodology that can capture even minute amounts of material. Consequently, nucleic acid sequenc- es, which may be amplified also in the case of a tumour, are crucial for an early diagnosis,’ the professor pointed out. Because it is minimally-invasive – unlike needle biopsy – the liquid biopsy approach can be repeated and used to monitor tumour progres- sion and therapy. Other advantages of liquid biop- sy include: prognostic information; easy sequential monitoring; plan- ning treatment monitoring; identi- fication of molecular modifications before and during tumour develop- ment; RNAseq studies; detection of infectious agents; and post trauma monitoring, plus the technological advantage of increased sensitivity and specificity of nucleic acid NGS and other products of omic sciences. Among the tumour components that are shed into the circulation, Salvatore explained, the three that are most likely to be clinically useful and have the greatest potential are: investigated, there is great and potential for cancer treatment. ‘Since cancer is a genetically driven disorder the sequencing of tumour derived DNA and RNA is very promising, not only in terms of understanding the pathogenesis of cancer, but also in the early identification and moni- toring of tumour derived material thereby acting as biomarkers of the y r a h d u a h C v a n i h b A / k c o t s r e t t u h s © Quality and innovation from the Czech Republic Hello! You are invited! The Czech Ministry of Industry and Trade and some special medical firms are eager to meet delegates and visi- tors for an early evening get together on Tuesday, 13 November at Medica. The companies include: Advanced Medical Solutions develops, manufactures and sells diagnostic and therapeutic devices that include portable ultrasound and occlusion plethysmography with powerful software for arterial, venous and lymphatic diagnostics. Biomag manufactures pulsed mag- netic therapy devices and its pat- ented 3-D Pulse magnetic therapy has a quality verified by professionals in 30 countries all over the world, the firm reports. Brno University of Technology focuses on scientific research and putting unique ideas into action. Eyrina produces a semi-automatic non-mydriatic fundus camera. Special Medical Technology mainly develops and manufactures devices for electro- and cryosurgery, with a broad range of applications in many fields. Devices are developed and manufactured in the Czech Republic and approved according to EU stand- ards. Synthesia produces naturally-based oxidised cellulose for biomedical and technical use. Its products are sold commercially under the brand name OKCEL. VUP Medical has more than 60 years in research and innovative medical equipment design, and focuses on implantable and non-implantable medical devices. Watek technology produces ultra- clean water primarily for medical, laboratory and pharmaceutical indus- try use. ‘Water treatment systems are designed in accordance with strict quality standards,’ the Watek con- firms. Compex/Jett Medical manufactures the deviceJett Plasma Lift Medical – the first patented direct current plasma device to examine skin. The product is manufactured entirely in the Czech Republic. EH @ MEDICA No 1 2018

4 M O N D AY @ M E D I C A Predictive potential of Big Data in the lab Big Data can be a critical tool in helping clinicians develop advanced patient health risk assessment and stratification models as well as leading to a new level of patient empowerment, reports Mark Nicholls. Professor Josep Roca outlined the benefits of Big Data in a laboratory con- text during the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Strategic Conference held in Mannheim, Germany, this June. Under the heading ‘Big Data for pre- diction in the lab’, he discussed how disruption through biomedical infor- matics technologies and how using Big data for prediction is bringing about paradigm changes for diagnostics. Stressing the importance of health systems relying on health-related date and analytical tools, he told European Hospital: ‘An ideal healthcare setting should facilitate an optimal support to care decisions and delivery by reducing the complexity of the massive amount of multi-disciplinary data being pro- duced every day and should improve efficiency of health outcomes both in terms of well-being and expenditures. ‘Such a health system relies on the availability of health-related data and analytics tools.’ During the session, Roca – Professor of Medicine at the University of Barcelona and senior consultant at Hospital Clínic of Barcelona – analysed the three forces currently driving pro- found healthcare transformations: · changes in biomedical knowledge · the burden of chronic conditions · the need for generating healthcare efficiencies. Roca also addressed the role of data science in the current health scenario, as well as opportunities and barriers we are facing for adoption of big data ana- Comorbidity Network diagram for elderly COPD in the Catalan population, 2018. Source: Ákos Tényi areas need to be addressed to face these current challenges: cloud-based tools and services; enhanced clinical predictive modelling; implementation and evaluation; and governance and regulatory aspects. His conclusion: ‘A proper imple- mentation strategy, tackling privacy and regulatory constraints, would highly contribute to enhance health- care outcomes and patient experi- ence of care while reducing costs and improving the health of populations.’ Josep Roca MD is Professor of Medicine at the University of Barcelona, senior con sultant at Hospital Clínic of Barcelona and senior researcher at IDIBAPS in Spain, as well as Adjunct Professor at the University of Southern Denmark (Odense). He is the author of more than 300 original articles in peer-reviewed journals and several book chapters, review articles and books. His two main interests are chronic patients management (integrated care and systems medicine) and gas exchange and skeletal muscle bioenergetics in chronic patients. in l y t - ics h e a l t h . Roca and team have been using Big Data to collect data for projections on the healthcare impact of chronic obstructive pulmonary disease (COPD) over the next 15 years (see diagram). Enhanced clinical predictive model- ling, he said, and personalised diag- nostic and treatment tools – such as clinical decision support systems and patient decision support systems – can contribute to the acceleration of trans- fer of scientific evidence to practice, helping in the identification of gaps in care and in targeting interventions to the most appropriate sub-populations of patients. ‘Overall, the unique poten- tial of information from health data within a digital health framework is the enhanced extraction/generation of novel knowledge through the integra- tion of multiple information sources,’ Roca added. ‘Develop ment of new models for patient stratification based on this foundation would help to define the most appropriate action plan for patients, s u p p o r t - ing the vision of personalised health- care. Moreover, deployment of big data analytics in an integrated care setting should contribute to patient empowerment through efficient patient decision support systems.’ In terms of clinical outcome, the potential of Big Data is that it can support healthcare professionals in the development of patient health risk assessment and stratification models, integrating health information from informal care, formal healthcare and biomedical research, while creating new knowledge on disease mecha- nisms. In turn, Roca suggests, this will gen- erate healthcare efficiencies and facili- tate patient empowerment provided that an appropriate implementation setting is achieved. However, he notes that barriers and opportunities to enable the potential of Big Data applications in health have been reported recently in several pub- lications. His view is that four strategic The all-in-one molecular laboratory system Walkaway automation lab-in-the-box design of The LabTurbo SP-qPCR All-in- one system offers true auto- mation for the molecular laboratory, the manufactur- er reports, adding that this ‘delivers testing confidence and laboratory efficiency’. ‘LabTurbo fully auto- mates the complete work- flow of molecular diagnostic laboratories. The sample-to- result procedure includes: automatic sample transfer from primary tubes, DNA/ RNA extraction, PCR reac- tion setup, qPCR thermo- Taigen is at Medica Hall 17 / Stand C61 cycling, and qPCR result analysis with graphs,’ the company explains. ‘As a true walkaway system, you can simply put the samples on LabTurbo system and the final results will be ready for report in three hours.’ LabTurbo is ideal for automating highly complex nucleic acid diagnos- tics procedure, the manufacturer adds. ‘It integrates nucleic acid purification, quantification with qPCR, and nor- malisation into a complete procedure. It can also fully automate the bisulfide conversion process for methylated DNA purification for epigenetics.’ The system also detects viral load in serum/ plasma samples with qPCR nucleic acid quantification to overcome the chal- lenge of undetectable nucleic acid con- centration range by spectrometer. ‘For example,’ LabTurbo reports, ‘the sys- tem performs GADPH quantification, DNA concentration normalisation, and PCR setup in an integrated procedure for completely automated diagnostic procedure. This is also ideal for non- invasive prenatal diagnosis (NIPD) with digital PCR technology.’ The LabTurbo complete automa- tion covers applications such as infec- tious disease screening, virus detection (HIV/HBV/HCV), bacteria detection, HLA-typing, personalised medicine, and many more. ‘The versatile system is suitable for target detection from whole blood, serum/plasma, saliva, swab, biological fluids, tissues, cells, and etc,’ the firm reports. The company’s products support FDA-approved nucleic acid testing for infectious disease screening in human blood. ‘The advanced automation, consistent performance, and reliable results from LabTurbo systems are the keystone for the routine infectious screening in US blood supply.’ EH @ MEDICA No 1 2018

6 M O N D AY @ M E D I C A Molecular diagnostics and antibiotic stewardship Screening with multiplexed kits Antibiotic stewardship is becoming a critical concern in hospitals as antibiotic resistance spreads globally and some organisms become resistant to antibiotics of last resort. Molecular diagnostics can play a role in antibiotic stewardship programs by providing timely and accurate advice to clinicians on which antibiotics to use, Professor Keith Stanley advises. in Antibiotic resist- ance the European Union is estimated to result in 25,000 deaths per annum and costs 1.5 billion euros in healthcare costs and productiv- ity losses. Yet, more worrying is the emergence of bacteria with plasmid- borne resistance against colistin - an antibiotic of last resort. For Gram-positive bacteria the variety of resistance genes is limited and molecular diagnostics can pro- vide useful information about treat- ment of a patient shortly after a blood culture bottle flags as positive. The situation for Gram-negative bacteria is more complicated as there are a large number of resistance genes, many of which can be trans- mitted between different bacterial species. The CDC has listed carbap- enem-resistant Enterobacteriaceae (CRE) as an urgent threat in antimi- crobial resistance and a number of companies manufacture molecular diagnostic kits which can identify the five major types of resistance in a few hours. Those kits are useful for routine screening, but for epidemiology or infection control a highly multiplexed molecular diagnostic kit is required that encompasses a large number of minor as well as major CRE genes. It is likely that the highly multiplexed kits will become the norm for screen- ing applications, as well giving hos- pitals immediate access to infection control issues. Ideally, diagnostic tests should advise the clinician of the best clini- cal strategy rather than just inform- ing about the content of individual sequences of resistance gene found in the sample. This requires a more complex strategy where the spec- trum of resistance genes that would preclude use of a particular antimi- crobial agent are tested. If all genes that might give resistance to that class of antibiotic are missing, then treatment with that drug is recom- mended. Because the number of resistance genes is large a probability considera- tion based on epidemiology has to be included so that a clinical course can be recommended with a certain probability of success. This type of analysis requires a highly multiplexed PCR system which can detect multi- ple sequences from a single sample (see figure). This approach was recently car- ried out for difficult to treat urinary tract infections and might be the forerunner of similar tests for other conditions. Improved antibiotic stew- ardship could be well served if the microbiologist can advise the best antibiotic to use, thus preventing over prescription of last resort antibi- otics in critical hospital settings. The issue is whether a result can be obtained fast enough to be of value, and what probability of suc- cess would be acceptable to the clinician. In this context, the ability to detect the presence of bacteria and resistance gene in EDTA blood before culture is an important step forward. Microbial resistance is also becom- ing of major importance in sexually transmitted infections. Mycoplasma genitalium is not easy to culture, so nucleic acid testing is the only feasi- ble route for diagnosis of resistance. Unfortunately, macrolide resistance has become widespread and is very Before his move to Australia, Professor Keith Stanley was an academic at the University of Cambridge and the European Molecular Biology Laboratory. After he invented Multiplex Tandem PCR, which enables quantitative analysis of large multiplexes, he launched the molecular diagnostics company AusDiagnostics, which works closely with customers to develop novel diagnostic solutions. common in some patient groups. A particular concern is Neisseria gonorrhoeae, which has recently been given ‘superbug’ status having acquired resistance to ceftriaxone, which is the last remaining option for first-line treatment. The rise of resist- ance in STIs argues for more complex STI diagnostic screening encompass- ing both infectious agent and resist- ance genes. A highly multiplexed assay for bacterial ID and resistance genes can be used to predict a possible treatment based on knowledge of the epidemiology of infections. Note the ‘Diagnosis’ at the bottom left hand side of the results screen. Looking for the stamp of quality? Enter the UK’s global platform ‘Medica attracts over 5,000 exhibi- tors from 70 countries and plays host to tens of thousands of visitors every year. It is a prime opportunity for United Kingdom’s medical companies Over in the United Kingdom Pavilion (Hall 16) you can expect quality among the latest medical devices, diagnostic software and digitally-ena- bled technologies produced by nearly 100 pioneering British health technol- ogy companies. ‘With over 97,000 people working in the UK’s HealthTech sector, it’s the life sciences’ biggest employer, and its importance has rightfully been recognised by the UK Government, forming a key component of their industrial strategy,’ reports The Association of British HealthTech Industries (ABHI), which leads the pavilion and supports the exhibitors. With such activity set to bolster what is already an incredibly strong industry, UK companies are now looking for the right trading opportu- nities to export their technologies and develop new business. ‘The UK has long been a leader in healthcare. We have world class universities, dynamic companies and the biggest single-payer health sys- tem on the planet, all adding up to what is an incredible ecosystem of innovation and medical excellence,’ Paul Benton, International Managing Director of ABHI, underlines. ‘It’s why overseas companies want to partner with our UK manufacturers and it’s the reason the UK carries significant weight when it comes to exploring international markets. It is, in short, a stamp of quality and we are proud to be at Medica once again to showcase many examples of this.’ The United Kingdom Pavilion is at Medica Hall 16 / Stand G19-4 EH @ MEDICA No 1 2018

8 M O N D AY @ M E D I C A High-quality transducers made for a few dollars Coming: Cut-price ultrasound application at very low costs,’ he pointed out. Engineers have developed a new high-quality ultrasound transducer that could dramatically lower the cost of ultrasound systems. Report: Mark Nicholls The innovation – created by a team from the University of British Columbia in Vancouver, Canada – is portable, wearable and can poten- tially be powered by a smartphone and the study team feel it will have benefits for making ultrasound more widely available, particularly in devel- oping countries Study lead, Dr Carlos Gerardo, from the university’s Department of Electrical and Computer Engineering, points out that, whilst ultrasound is safe, non-invasive and the world’s number one medical imaging modal- ity, high quality hospital ultrasound systems remain expensive. ‘This limits the number of machines available in a hospital and therefore creates long waiting times for patients,’ he explained, ‘so, we thought about a way to create high quality ultrasound transducers at a reduced price.’ Hospital ultrasound machines cur- rently use piezoelectric crystals as their transducers – effectively small ceramic tiles which, when a voltage is applied to them, expand and con- tract, generating ultrasound waves. ‘Conversely, these piezoelectric crystals generate electrical voltages when they are squeezed by external ultrasound waves; these voltages are then read by a computer and an image is displayed on a computer screen,’ Gerardo explained. ‘For our research, we replaced the traditional piezoelectric transducers with new drum-based CMUT technology using low-cost materials. This resulted in a simple fabrication process to create high-quality transducers for only a few dollars.’ Transducer drums have typically been made out of rigid silicon mate- rials that require costly, environment- controlled manufacturing processes. However, the high manufacturing costs of CMUTs - capacitive microma- chined ultrasonic transducers – has been countered by the researchers by the use of plastic-like materials instead of semiconductors. Gerardo explained that, by using a photosensitive polymer resin called SU-8, with fewer fabrication steps, the cost was dramatically reduced, and with the added bonus that the plastic-like materials actually boosted the device sensitivity. ‘This enabled the creation of high-quality ultra- sound transducers for biomedical ‘Our technology uses tiny vibrat- ing drums made of polymers (poly- CMUTs), each with a diameter of around 1/10th of a millimetre. We have thousands of these drums in our transducer that vibrate at the same time and produce ultrasound waves. ‘The benefit for the medical field is that this technology has the potential to reduce the current cost of ultra- sound machines used in hospitals. If the cost of the machine is reduced, then a hospital can afford to buy more ultrasound systems and reduce the waiting times for patients.’ The team envisages creating an ultrasound system cheap enough for family doctors to conduct ultra- sound scans for immediate – and early – diagnosis, instead of refer- ring patients to an ultrasound clinic or hospital. ‘Imagine a family doc- tor could immediately confirm the presence of a breast cancer or a heart problem in the same room using a portable (and ultra-cheap) ultrasound scanner connected to a smartphone,’ he suggested. Hospital grade ultrasound sys- tems cost more than $100,000, while cheaper versions are $20,000 and recently Butterfly Network has unveiled i-Phone compatible ultra- sound that will cost $2,000, but the Vancouver development could see ultrasound-type equipment fall to as cheap as $100. ‘We envisage creat- CMUT enlarged under microscope (above) and CMUT linear array (left). performance ultrasound systems for an extremely affordable price.’ The transducers also couple more naturally into soft tissues, which in turn increases efficiency. They can also be fabricated small enough to be mounted on a stent to look at the interior of veins and arteries, Gerardo suggested, or be fabricated in large areas to cover large portions of skin and create an even clearer ultrasound image. The new transducer created by Gerardo, working with Professors Robert Rohling and Edmond Cretu, has involved hundreds of hours spent over the past three years in the uni- versity’s microfabrication lab. While the new transducer is being regularly updated with fresh prototypes, the electronic circuitry and software remains in develop- ment and researchers acknowledge the most challenging element will lie ahead in liaison with regulatory authorities and proving the effective- ness of the probe in clinical trials. ing a portable ultrasound system so affordable that people at home can acquire it,’ Gerardo confirmed. ‘The reason we say it can be powered by a smartphone is the low voltage levels required to operate it. We use 12V, but it can be reduced to less than that, for instance we operated these transducers in our lab using a 9V battery. ‘This transducer has the potential to reduce the costs of high-end ultra- sound machines and enhance their performance. People in developing countries and struggling economies will benefit the most, as they will have the opportunity to acquire high- Contrast-enhanced ultrasound for renal masses Report: Mark Nicholls Contrast enhanced ultrasound (CEUS) has proved in trials to be more accu- rate than computed tomography and MRI and can help eliminate the need for unnecessary biopsies and surgery. Led by Dr Richard Barr, Professor of Radiology at Northeast Ohio Medical University, the team has been using CEUS since 1999 and, for the spe- cific study, focused on 721 patients referred contrast-enhanced ultrasound (US) with 1018 indeter- for SP-qPCR All-in-one System Automated DNA/RNA diagnostic platform Extraction PCR Setup qPCR Report Booth H17C61 Automate the entire molecular lab workflow Lab in the box Sample to result Simply put samples in and get results in 3 hours Cost-effective High Versatility Open for qPCR 100% hands-free and avoid handling errors Various sample types and customizable program Suitable for commercial qPCR kits Taigen Bioscience Corporation www.labturbo.com minate renal masses between then and 2010. Following CEUS examina- tions, 367 of the patients were spared biopsy, surgery or close follow-up. ‘Because all malignant renal masses have blood flow, if no enhancement is present, they are benign 100%,’ Barr explained. ‘If we exclude vascular abnormalities and infections – usually identified clinically – most masses with blood flow are malignant. Therefore, using CEUS, we can confirm a mass is benign without a biopsy or surgery.’ CEUS uses liquid suspensions of biocompatible microbubbles, which are slightly smaller than red blood cells, and are injected into an arm vein during an ultrasound scan. Each has a unique sonographic characteristic, enabling radiologists to use specific ultrasound contrast to see a contrast- only image, as well a standard image at the same time. CEUS does not expose patients to ionising radiation and the microbubbles present no risk of kidney or liver damage. Indeterminate renal masses are a common clinical problem with more than half of patients aged over 50 esti- mated to have at least one renal mass. Many renal masses are found inciden- tally during an imaging examination and most are benign simple cysts. The purpose of the research, ‘Evaluation of Indeterminate Renal Masses with Contrast-enhanced US: A Diagnostic Performance Study’, was to determine the use of contrast material-enhanced ultrasonography in the characterisation of indeterminate renal masses. With 100% sensitivity, the results offered a conclusion that CEUS evalu- ation is a highly-sensitive and specific method for characterisation of inde- terminate renal masses. ‘Because we can 100% confirm a lesion is benign, no surgery or biopsy is needed. That is the big benefit for patients,’ Barr added. ‘We have followed our first 1,018 cases now for 10 years and none of the renal masses without blood flow became malignant. ‘Also, positive patients can be treat- ed and not watched to see if lesions grow. As for clinicians, they can be confident in the diagnosis and not have to be concerned about following up the patient.’ In terms of diagnosis, he said they can predict with high probability if a mass is benign or malignant, though acknowledged that in terms of specific diagnoses more work is needed. Overall, the Northeast Ohio team has collected an additional 2,000 cases and is working on additional features to determine whether they can provide a histologic diagnosis of the malignancies. ‘Some renal cancers are very slow growing,’ Barr noted. ‘If we can select these out, older patients may not need to have surgery or treatment but just be watched to make sure the lesion is not growing.’ With findings that show CEUS is a ‘very robust technique with an Dr Richard Barr is President of Radiology Consultants Inc. in Ohio and a Professor of Radiology at North-eastern Ohio Medical University, Youngstown, Ohio. The research is performed at Southwoods Imaging in Youngstown, Ohio. His more than 100 scientific articles show particular in breast imaging, contrast-enhanced ultrasound, and elastography. He has also published two elastography books, plus several book chapters. From January, he will be the editor-in-chief of the Journal of Ultrasound in Medicine. interests extremely high predictive value,’ Barr concluded: ‘CEUS, which is available worldwide, is more accurate than CT and MRI because we have a contrast only image, so we can see very small amounts of contrast. ‘Ultrasound also has a much small- er slice thickness, so we can iden- tify 1mm enhancing nodules within a renal mass. CEUS can be used in patients with renal failure.’ EH @ MEDICA No 1 2018

1 0 M O N D AY @ M E D I C A Artificial intelligence system impr heart disease diagnosis Cardiologists in the UK are trialling an artificial intelligence (AI) system that will help better diagnose heart disease. Report: Mark Nicholls Devised by researchers from the University of Oxford, it can predict heart disease and cardiac events from ultrasound stress test images with ini- tial results showing that the AI system is far more accurate than conventional techniques. Paul Leeson, Professor of Cardiovascular Medicine at the University of Oxford - who leads the development team with PhD student Ross Upton - said the system is cur- rently being trialled in a “real world cardiology” environment in 15 units across the UK to formally assess its effectiveness and accuracy ahead of a formal publication of the results and a clinical roll-out. With current examination tech- niques, it is estimated that the diag- nosis is wrong in up to 20% of cases, leading to patients either being sent home with the risk of having a cardi- ac event, or undergoing unnecessary procedures. clinician on whether it believes there is the risk of a patient having a heart attack or not, and identifies the loca- tion of disease. Professor Leeson, who is also a Consultant Cardiologist at the John Radcliffe Hospital and Professor of Cardiovascular Medicine at the University of Oxford, said: “Ultrasound and stress echo are one of the most widely used imaging modalities to investigate heart disease. At the moment as cardiologists, we look at these images and try and identify changes with the eye. We are pretty good at doing that but my feeling was that we could do this better.” By revisiting images and working with returning patients, they have been able to extract additional infor- mation to look at different biomark- ers and approaches to try to improve stress echo findings. He continued: “With a particular focus on ultrasound image data, we have broken that down into differ- ent bits to see what parameters we can pull out of these echo images. Because we had follow up extend- ing over many years we were able to take that ultrasound imagery and see what features are predicting who has events and who does not when a patient comes forward for stress echo. With knowledge of background history and what happens to them The Ultromics stress echo diagnostic support system generates a recommendation of positive if abnormalities in heart function are detected. The colour maps below identify where the disease is located in the left ventricle with colour coding to describe the severity of abnormalities detected The new AI system, developed from ongoing research studies at the University of Oxford Cardiovascular Research Facility, is set to significantly improve upon that. The company developing the technology is called Ultromics and the stress echo analysis software is called Echuity and is ultra- sound vendor neutral in that it works with images from any of the major ultrasound manufacturers. The pro- cess to construct the diagnostic algo- rithm involved extracting thousands of parameters from echocardiogram images and using machine learning to determine which parameters were most diagnostic of coronary artery disease. From that, the system gives a diagnostic recommendation to the subsequently, you can start to pick out very interesting predictors of who gets disease and who does not.” What emerged were good imaging biomarkers that could be applied pro- spectively within an algorithm to iden- tify individuals who are most likely to suffer heart disease or have a cardiac event. From images of the heart, the team developed ways of applying these techniques to provide accurate and a consistent results. To date, the system has an accuracy level equivalent to the best performing clinicians of a one in 10 error rate, but the researchers are keen to rigorously test this. That involved comparing how accurately clinicians are predicting outcome with how accurately the machine algo- rithm approach predicts outcome in 15 cardiology departments. Professor Leeson stressed: “We know we can get good results based on the data we have from our centre. What we want to do at this stage is confirm that the automated approach consistently pro- duces at least as good results as the best quality operator. However, “Of course, the cardiologist will still need to decide what to tell the patient and work out what the best management plan for the patient may be, but for the patient, increased accuracy may save unnecessary inva- When and when not to prescribe antibiotics Ultrasound aids ear infection diagnosis which is essentially a magnifying lens, battery, and light source – a virtually unchanged system since its introduction decades ago. With the otoscope, the clinician can only view the tympanic membrane (ear drum). However, accurately characterising the contents of the middle ear, on the other side of the membrane, is key to the accurate diagnosis and treatment of OM. A new device under development at OtoNexus Medical Technologies (Seattle, WA, USA) has the familiar form factor of a traditional oto- scope, but uses a novel air-coupled ultrasound tech- nology to provide the data physi- cians need to instantly and accurate- ly assess middle ear infections, the company reports. ‘This allows them to accurately differentiate when and when not to prescribe antibiotics.’ Otonexus is at Medica Hall 16 / Stand D10-1 Although traditionally an imaging modality, ultrasound also has appli- cations as a measurement tool. An innovative application is to assess ear infections. Otitis Media (OM), a middle ear infection, is the number one indica- tion for antibiotic prescriptions for children and the leading cause for surgery. This problem is global. Nearly every child will suffer at least one middle ear infection severe enough to see a health professional, and most will suffer repeat occurrences – up to a dozen or more in childhood. Multiple studies (including from the CDC) show diagnostic error rates averaging 50 percent, particularly in the key differentiation of viral from bacterial infection, and whether an antibiotic is appropriate. Thus, patients are often given the wrong treatment and are referred to special- ists more often than necessary. The problems from excessive antibiotic use are well known. Additionally, under-diagnosis can result in surgery or permanent hearing loss. The current tool used to diagnose middle ear infections is the otoscope, OtoNexus has partnered with Fraunhofer-IPMS (Dresden, Germany) – a global leader in MEMS develop- ment and manufacturing – to cre- ate a unique transducer, a type of CMUT (capacitive micromachined ultrasound transducer). ‘Unlike traditional ultrasound transducers needing gel or water coupling, these new CMUTs are optimised to operate through air in the human ear canal,’ the com- pany reports. ‘Furthermore, they are manufactured using semiconductor fabrication methods, making them easy to mass produce and far less expensive. Using these novel trans- ducers, along with hardware and algorithmic innovations, OtoNexus EH @ MEDICA No 1 2018 CONSOLE Full touch smart user interface FLAT PANEL Last generation of dynamic flat panels WELCOME TO OUR BOOTH 10F74 www.primaxint.com sales@primaxint.com COMPACT CARM WITH FLAT PANEL « ALL IN ONE » VIEW STATION Integrated touch screen monitors on the carm

1 2 M O N D AY @ M E D I C A New medical cameras and displays Detailed resolution, accurate colour reproduction, high brightness. Designing medical imaging sys- tems for surgical, ophthalmology and microscope-mounting applica- tions, Ikegami Tsushinki Co. Ltd, from Tokyo, Japan, is showing the latest additions to its range of medical cameras and medical-grade displays. ‘The new MKC-X800 is a progres- sive-scan camera with an ultra-high- sensitivity 4K-native CMOS imager,’ Ikegami reports. ‘Measuring just 34 x 40 x 40 mm, the camera head connects to a control unit giving access to functions such as mirror, flip and rotate, image correction and scene file access. The MKC-X800 can output in a variety of signal formats, such as quad-link 3G-SDI, HDMI 2.0. or 12G-SDI. Originated for the pro- fessional broadcast sector, the 12G SDI signal format allows easy 4K con- nection over a single coax cable,’ the report concludes. ‘These new cameras are ideal for capturing the precise colour and image detail of surgical operations,’ says Zeljko Romanic, Industrial & Medical Video Division Manager at Ikegami Electronics (Europe) GmbH. ‘The MKC-X800 can be mounted on a lightweight support stand or boom and is designed for easy setup by medical staff, allowing the entire system to operate automatically.’ The company also offers a diversi- fied range of medical grade displays. ‘The combination of 4K ultra-high definition imaging and the enhanced dynamic range display capabilities increases the quality threshold now possible in video signal reproduction,’ Ikegami notes. ‘Top of the range are the 27-inch 4K high luminance model MLW2750UHD and 31-inch 4K 2D/3D model MLW3110U, each delivering an unsurpassed 4096 x 2160 resolution. Both displays incor- porate 12GSDI and HDMI 2.0 inputs. Additional features include a new IPS panel with LED back lighting, multi- display modes, full-flat front panel design and full compliance with medical safety direc- tives.’ For storage applications, the Ikegami MDR-600HD digital video recorder can capture still images and Full-HD 1920 x 1080 video to its 500 gigabyte integral hard drive, or to USB-plus-in flash/HDD. ‘The recorder includes an easy-to-operate front control panel with a built-in 3.5- inch full colour LCD screen, hygienic membrane control buttons and easy- access forward-facing USB ports,’ Ikegami adds. ‘Operating features include still image capture, content search and image data transfer. A barcode reader, foot switch, remote controller and USB card reader are available as options.’ Ikegami is at Medica Hall 10 / Stand B12 Focus on lighting Yet again the lighting manufacturer ACEM, based in Bologna, Italy, has produced a new and valued medi- cal lighting system – the focusable ACEMSO15F – aimed for use in diag- nostics, minor surgery, intensive care and more. Physically, the round, function- al, wall, ceiling or trolley mounted ACEMSO15F is easy to grip and move and, for sterilisation, the han- dle is removable. The optional ABPS rechargeable battery powered system provides use during emergency situations, humani- tarian interventions, sudden black-outs, in field hospitals with- out UPS or power generators, and other conditions. The ABPS matches the powered performance, and a control panel on the structure allows management of the residual charge, the type of power supply, recharge status and electrical power supply presence. ACEM is at Medica Hall 10 / Stand B60 This offers: • 110,000 lux light intensity • An IR-free light beam • Light beam focusing • Colour temperature (CCT) of 4,500 K • Colour rendering index (CRI) of 97 • Low power consumption (25 W). • The LED arrangement produces uniform, homogeneous and shad- owless light. The ophthalmic eyeball scanner Echo-Son S.A. is at Medica Hall 9 / Stand B42 Echo-Son S.A. is showing PIROP, its state-of-the-art ophthalmic ultra- sonic device for biometry, visu- alisation and pachymetry of eye- balls (A+B+P Scan). ‘The user inter- face is based on touch screen tech- nology, which makes operation easy and user-friendly,’ the Polish firm reports, adding this summary: • A-SCAN – Ocular Lens Biometrics. A digital ‘A-scan’ tool for oph- thalmology, biometry and lens power calculation of intra-ocular implants. Complete and quick biometry ; measurement of all eye types; IOL formulas; post refrac- tive formulas; IOL power calcu- lation comparison; contact and immersion methods. • B-SCAN – Eye examination modern ‘B-scan’ tool for ophthalmology, interior eyeball imaging, retina, optic nerve etc. Probe frequency – 12/15 MHz. • PACHYMETER (P-SCAN) – Ocular Cornea biometrics. The up-to- date ultrasonic pachymeter (cor- Editor-in-Chief: Brenda Marsh Art Director: Olaf Skrober Editorial team: Wolfgang Behrends, Beate Schenk, Sascha Keutel Senior Writer: John Brosky Executive Director: Daniela Zimmermann Founded by Heinz-Jürgen Witzke ISSN 0942-9085 Correspondents Austria: Michael Kraßnitzer, Christian Pruszinsky. China: Nat Whitney France: Jane MacDougall. Germany: Anja Behringer, Annette Bus, Walter Depner, Cornelia Wels- Maug, Holger Zorn. Great Britain: Brenda neal thickness biometrics) has a very high sampling frequency (400 MHz) – a significant increase in measurement accuracy. 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Developers of BCIs rely on artificial intelligence, neural network models and big data to mitigate the effects of Alzheimer’s, Parkinson’s, epilepsy, and other neurodegenerative conditions, to develop even better prostheses, or ultimately to improve the human cognition. Examples… The beginning of the MoreGrasp pro- ject was marked by the idea of a ground-breaking further development of grasp neuroprosthetics activated by thought control. The aim was to develop a sensoric grasp neuropro- sthesis to support daily life activities of people living with severe to com- pletely impaired hand function due to spinal cord injuries. The motor function of the neuroprosthesis was to be intuitively controlled by means of a brain-computer interface with emphasis on natural motor patterns. After the three-year project came to an end, the breakthrough was reported by members of the project consortium, led by Gernot Müller- Putz, head of the Institute of Neural Engineering at TU Graz, which include the University of Heidelberg, University of Glasgow, two companies – Medel Medizinische Elektronik and Bitbrain – as well as the Know Centre. ‘In tetraplegia, all circuits in the p s a r G e r o M © Research success for the MoreGrasp consortium: With the help of reprocessed brain signals the mental control of neuroprostheses will be considerably simplified in future brain and muscles in the body areas concerned are still intact, but the neurological connection between the brain and limb is interrupted. We bypass this by communicating via a computer, which in turn passes on the command to the muscles,’ explains Gernot Müller-Putz, head of the Institute of Neural Engineering at TU Graz. The muscles are controlled and encouraged to move by electrodes attached to the outside of the arm and they can, for example, trigger the closing and opening of the fingers. This mental ‘detour’ of any move- ment pattern, so long as it is clearly distinguishable, is no longer necessary, as Müller-Putz explains. ‘We now use so-called “attempted movement”.’ In doing so, the test subject attempts to carry out the movement – for instance, to grasp a glass of water. Due to the tetraplegia, the occurring brain signal is not passed on, but can be meas- ured through an EEG and processed by the computer system. Müller-Putz is extremely pleased with the success of the research. ‘We are now working with signals that only differ from each other very slightly; nevertheless we manage to control the neuroprosthe- sis successfully. For users, this results in a completely new possibility of making movement sequences easier – especially during training.’ How does the brain talk with our arm? The body doesn’t use English, or any other spoken language. Biomedical engineers are developing methods for decoding the conversation, by analys- ing electrical patterns in the motor control areas of the brain. In this study, the researchers at the Rehabilitation becomes a game y t i s r e v i n U y r o m E , i m K a n o B y b n o i t a r t s u l l I © Biomedical engineers are developing methods to decode the conversation between brain and arm, by analysing electrical patterns in the motor control areas of the brain Emory University leveraged advances from the field of ‘deep learning’. The computing approaches, which use artificial neural networks, let research- ers uncover patterns in complex data sets that have previously been overlooked, lead author Dr Chethan Pandarinath points out. The research team developed an approach to allow their artificial neu- ral networks to mimic the biological networks that make our everyday movements possible. In doing so, the researchers gained a much better understanding of what the biologi- cal networks were doing. Eventually, these techniques could help para- lysed people to move their limbs, or improve the treatment of people with Parkinson’s, says Pandarinath, an assistant professor in the Wallace H Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, USA. ‘brain-machine For someone who has a spinal cord injury, the new technology could power interfaces’ that discern the intent behind the brain’s signals and directly stimu- late someone’s muscles. ‘In the past, brain-machine interfaces have mostly worked by trying to decode very high- level commands, such as, “I want to move my arm to the right, or left”,’ Pandarinath points out. ‘With these new innovations, we believe we’ll actually be able to decode subtle sig- nals related to the control of muscles, and make brain-machine interfaces that behave much more like a person’s own limbs. 1 4 M O N D AY @ M E D I C A Understanding the brain and optimising how it works Brain-computer interfaces A world where machines can be controlled by thought alone - such is the promise of so-called brain-computer interfaces (BCI). BCIs are both hardware and software communication systems that read brain and nerve signals, convert those into electrical signals and translate human thoughts into machine commands. Evolv Rehabilitation Tech is at Medica Hall 4 / Stand F10 Spanish firm Evolv Rehabilitation Technologies S.L. reports that its flagship product, VirtualRehab, is a pioneering CE certified rehabilita- tion platform that uses virtual reality, motion capture systems, and ‘gami- fication’. ‘VirtualRehab has been used by thousands of patients of all ages and levels of ability in over 100 reha- bilitation centres in 20 countries,’ the tech firm adds. ‘Developed in con- junction with leading international neurologists, therapists and research- ers, VirtualRehab helps people of all disability levels to have rehabilitation in clinics as well as at home through game-like task-specific activities. IAE – C20 • A new compact lightweight housing, specifically designed for mobile equipment. • A low weight, less than 8.5 kg, combined with compact dimensions, 116 mm diameter and 342 mm length, allows significant reductions in the equipment supporting structures. • A range of tube inserts up to 54 kW peak radiographic power at high rotation speed is available for this unit. Visit IAE at MEDICA – Hall 10, Booth B 73 • www.iae.it Exoskeleton enables autonomous walking ‘Wandercraft’s exo is the first auton- omous walk exoskeleton. It is also the first to have the potential to restore outpatient autonomy,’ the maker reports. ‘Delivering autonomous and realistic ambulation requires two complementary technologies: dynamic robotics algorithms and mechatronics, that accommodate unbalanced situations during the stride and calculate trajectories and foot placement at each point of the gait cycle to re-create balance; then 12 actuated degrees of freedom, to allow physiological movements.’ The manufacturer adds that its 2018 Rehab Centre version offers: • Autonomous walk and sitting/ standing manoeuvres, without crutches. • Eliminates strain upon upper body from use of crutches, allowing for medical hypotheses on the impact of higher treatment repeti- tion and intensity, without upper limb damage or excessive energy consumption. • More realistic patient posture and gait, allowing for hypotheses on the impact of better leveraging neural plasticity. A strong emphasis has been put on a patient’s tolerance of the exo, to allow repeated, frequent therapy sessions. In the first clinical trials, patients remained several hours in a Wandercraft SAS is at Medica Hall 4 / Stand H22 row in the exo under medical super- vision, with no significant fatigue nor skin lesions. ‘Medical teams working with Wandercraft plan to leverage the exo’s unique self-balancing and gait realism to validate hypotheses on its potential to increase treatment efficacy in three areas,’ the firm adds: • Rehabilitation, with hypotheses on factors such as: a more realistic gait; increased doses allowed by the absence of strain on upper limbs and lower energy consump- tion; could enable more efficient and effective rehabilitation. • Addressing associated diseases resulting from sedentary life in a wheelchair, with hypotheses on the impact of more realistic gait and potentially higher doses of treatment. EH @ MEDICA No 1 2018

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