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L A B O R AT O RY 9 , or despite automation? VID-19 the course of time we reduced the team in the core lab and transferred some team members to special diag- nostics, haematology, coagulation or areas such as serology or toxicology.’ A hospital lab always reflects the foci and departments of an insti- tution as a whole. In your case, paediatric and adult oncology are major departments. How does this affect your lab? ‘We see a significant demand by the oncology departments and this plays a major role in the lab. We were able to transfer several of the clinical chemistry staff mentioned above to oncology. In haematology, we have a Sysmex system with digital mor- phology followed by flow cytometry. Among the areas that are not part of the central lab are molecular biol- ogy, where PCRs for oncology and pathology are performed.’ Talking about PCR: how does COVID-19 affect your lab? ‘Not so much. We do have a full Cobas 6800 system. The main issue, however, is the fact that we don’t have enough tests. Currently, we use Corona antibody tests.’ Do you only test your own patients and staff or do you also receive samples from outside to process? ‘We receive very few external sam- ples from office-based physicians. Our problem is the fact that non- hospital labs receive priority for tests. We only receive about 1,000 test units per week for molecular biol- ogy. Technically, we would have the capacities for many more tests. I per- sonally was not tested, since the lab is considered a closed-off zone. The situation is obviously very different for our patients and the care staff.’ Formerly a laboratory physician in Magde- burg, Germany, 20 years ago Dr Horst Mayer joined the Department of Clinical Diagnostics at Karlsruhe Hospital, where he became managing senior physician. The science behind 3-D printed intensive areas and transfer peo- ple to more ‘demanding’ tasks? ‘When we installed the first auto- mated lab system in 2009, we were lucky because the four employees who became redundant retired – we did not have to replace them. Over ) 3 ( y r o t a r o b a L s n o i t a c i l p p A l a c i n i l C D - 3 F S U f o y s e t r u o C 3-D printed swabs Her lab is printing 324 swabs a time per printer using Formlabs surgical guide resin, a process taking between 15 to 30 hours depending on printer model used. After the swabs are printed, they are cured, individually wrapped, and autoclaved, and ulti- mately delivered to USF and Tampa General Hospital’s infectious disease labs for coronavirus testing. More than 3,000 Formlabs 3-D printer customers worldwide have signed up to print COVID-19 response parts. ‘Formlabs and its partners have produced more than a million swabs so far, and thousands of other medical components and PPE supplies,’ said Hollaender. * Healthcare groups wanting to legally pro- duce swabs may contact Dr Decker: email@example.com. www.healthcare-in-europe.com www.gbo.comGreiner Bio-One GmbH | Bad Haller Straße 32 | A-4550 KremsmünsterPhone: (+43) 75 83 67 91-0 | Fax: (+43) 75 83 63 18 | E-mail: firstname.lastname@example.orgThe most widely used materials in medical technology and research Opaque or transparent Shatterproof and safe Inexpensive and lightweight Flexibility at the highest level Only plastic can do thisWhere would we be today without plastic?More information on our websiteCOVID-19 shows that medical plastic products save lifes
1 0 M E D I C I N E Abbott: Creating Life Changing Technology An increasingly dynamic cardiovascular presence In the world of laboratory diagnostics, ‘Abbott’ is a household name. Few people however are aware of the fact that the company, headquartered in Illinois, USA, is also leading in other fields. A number of innovations in cardiac and vascular diagnostics and therapy might soon put Abbott in the limelight. Dr Angela Germer, Regional Director DACH, and Volker Keller, Head of Marketing DACH, Vascular at Abbott, updated Daniela Zimmermann on the company’s most recent developments and the plans for the future. Abbott’s German cardiovascular busi- ness area operates from Wetzlar and Eschborn, in the Frankfurt/Main region, with Vascular und Structural Heart managed in Wetzlar. Whilst the Structural Heart team focuses on the treatment of structural heart disease (SDH), the Vascular team’s exper- tise lies in diagnosis and treatment of vascular conditions with systems to assess vascular physiology, guide wires, and drug-eluting, as well as non-drug eluting, balloons and stents. OCT and FFR to avoid unnecessary stents Today, some patients receive stents without proven ischaemia, on suspi- cion so to speak. Usually, two tech- niques are used to assess ischaemia: either fractional flow reserve (FFR) or resting full-cycle ratio (RFR). A spe- cially designed pressure wire looks for drops in pressure caused by a stenosis. If the pressure drops signifi- cantly, the oxygen supply to the heart is impeded, says Dr. Angela Germer. firstly, Abbott uses a two-pronged approach to ensure that stents are implanted when and where clini- cally needed and to improve patient outcomes: the guidewire PressureWire™ X uses wireless data transmission, thus facilitating ischae- mia assessment by FFR; secondly, the Abbott-developed imaging solution OCT (optical coherence tomography) which allows precise measurement of vessels. ‘With this approach, we aim to optimise percutaneous coro- nary interventions, PCI for short, and to increase the likelihood that the right stent is placed at the right location,’ Dr Angela Germer explains. OCT delivers high-resolution colour images to monitor vessels prior to the intervention as well as in the follow- up when the stent is checked for correct placement and functionality. Abbott supports physician training From left: Volker Keller, Head of Marketing for DACH, Vascular at Abbott, Dr Angela Germer, Regional Director DACH and Astrid Tinnemans, who heads Public Affairs in Germany, updated Daniela Zimmermann on the company’s most recent developments and its plans for the future. with modern technologies, such as virtual reality (VR). In cooperation with several hospitals, the company recorded catheter-based procedures, such as FFR und OCT, and turned them into 3-D simulations to be used with VR headsets. ‘Thus, inter- ventions can be practised virtually, which increases patient safety during the actual procedure,’ Volker Keller points out. Abbott and the interna- tional cardiologist working group (AGIK) jointly organise workshops at trade fairs and congresses, and in hospitals, to provide in-depth training for clinical staff. The pressure wire is also used to diagnose microvascular heart disease which, in Germany alone, affects 175,000 people, Dr. Germer says: ‘This condition is rather frequent among cardiac patients, but difficult to diagnose. Many patients present OCT delivers high-resolution images of vessels several times without the cardiologist being able to detect the root cause. Our PressureWire X, combined with a dedicated software solution, can help detect minute deposits in the vessels and thus identify the disease.’ The highly specialised Abbott stent portfolio covers the many require- ments the tiny support structures have to fulfil in the different anato- mies. Stents for the femoral artery, for example, must be able to with- stand enormous biomechanical forc- es, such as torsion. ‘The nitinol wires in our Supera stent are not lasered but woven,’ Germer explains. ‘This unique technology makes Supera much sturdier than conventional stents, whilst maintaining its flexibility.’ Closure system accelerates patient mobility Perclose ProGlide, the tried and test- ed closure system that deploys suture after endovascular procedures with a femoral puncture larger than 5F without the use of collagen, is now also indicated for the femoral vein. ‘A suture is placed right at the ves- sel wall and the edges are joined again initiating primary healing. The closure can be tested right after the intervention. Unlike conventional sutures, Perclose ProGlide allows the patient to get up and move around quickly,’ explains Dr. Germer. Thus, hospital length of stay is reduced and accompanying procedures, such as a bladder catheter, can be avoided. Another advantage: If re-access is necessary, which is, in fact, the case with several conditions, the very same site can be used, even right after the initial procedure. Today, patients benefit hugely from implantable cardiac support systems, such as LVAD (left ventricular assist device). Abbott is currently devel- oping the next-generation of such When classic ventilation therapy fails in COVID-19 cases a device: FILVAS, fully implantable left ventricular assist system. It has no external components, such as battery packs or charging ports, which patients have to carry 24/7. FILVAS was recently designated a Breakthrough Device by the USA’s FDA. ‘Obviously, the new implant has to be charged regularly as well,’ Keller explains, ‘but FILVAS does this by induction via an implanted coil.’ Since energy sup- ply does not require opening the abdomen, patients can bathe, swim, enjoy the sauna – these are activi- ties that are almost, or even entirely, impossible with LVAD. Not to men- tion the fact that in conventional systems the external energy supply opening is a potential door for infec- tions to enter the body. AI algorithm calculates infarction risk Abbott not only uses diagnostic and treatment devices to improve cardiac patient care but also designs solu- tions based on artificial intelligence (AI). A recently developed AI-based algorithm to assess infarction risk is about to be used in clinical settings. The Abbott R&D team benefited from the in-house lab medical expertise: ‘Our algorithm correlates troponin values with other patient data, such as age, gender or prior disease,’ Keller points out. ‘This allows a detailed assessment of individual infarction risk.’ Prior to the commercial launch of the algorithm, clinical tests need to be concluded but, so far, the studies have yielded very promising results [Circulation: https://doi.org/10.1161/ CIRCULATIONAHA.119.041980]. With these ambitious projects in the wings, Abbott is well positioned to expand its reputation beyond the lab and have a strong impact in car- diovascular medicine. Extracorporeal therapy use rises ‘As the coronavirus spreads and infec- tions with COVID-19 further increase throughout Europe, Extracorporeal Membrane Oxygenation (ECMO) therapy turns out to be a neces- sary option for patients with severe courses,’ Xenios AG reports. The company’s ECMO consoles can pro- vide support in cases of severe pneumonia and ARDS with lung failure. ‘However,’ the company points out, ‘in contrast to the venti- lation methods usually used in these cases, the extracorporeal method is usually only used if the classic venti- lation therapy is not effective or not effective enough. ‘For critically ill COVID-19 patients with acute lung failure and refrac- tory hypoxemia, despite use of all standard therapy related measures, our treatment often remains the last therapeutic option and, in the best case, is a lifesaver for these patients,’ adds Dr Jürgen Böhm, Chief Medical Officer of Xenios. Bypassing lung function, the sys- tem clears the patient’s blood of carbon dioxide outside the body and enriches it with oxygen, giving lungs time to heal. ‘Because of the increase of critically ill COVID-19 patients, more physicians will opt for ECMO therapy.’ The company reports significantly higher demand for the devices and patient kits and has increased production of ECMO consoles. The devices are already in use in many COVID-19 hot spots such as in Italy, Spain and France, and beyond Europe. China’s most affected region Wuhan received a delivery of ECMO consoles and patient kits in February. ‘Our biggest challenge now is availability of specific components for our products,’ said Dr Andreas Terpin, Chief Executive Manager of Xenios, who also underlined the need to meet various standards, for example, the CE mark and FDA clearance (approved by the USA’s FDA through Fresenius Medical Care North America earlier in 2020). The system is available in more than 50 markets worldwide. Training intensity has been ramped up to ensure safety and straightforward use of the devices and is provided internationally via video transmission. EUROPEAN HOSPITAL Vol 29 Issue 2/20
M E D I C I N E 1 1 Advancing personalised medicine in clinical routine The virtual medical assistant and digital patient twin of all information about a patient and their anamnesis: radiological images, information on underlying medical conditions and previous surgery as well as molecular-genet- ic data. ‘This is much more com- plex than the electronic patient file which we already have,’ Neumuth observes. The data in the patient file has not yet been linked in a meaning- ful way, so comprehensive, patient- specific analyses supported by AI is not yet possible. However, the digital twin now ‘paves the way for the step from the analogue into the digital world,’ he believes. This also includes storing treat- ment steps, playing through options, and updating information, explains the project manager. This objectivis- es medical work, makes information accessible to all experts in the team in equal measure and facilitates improved prediction of the effective- ness of treatment. During diagnosis and therapy, the information of the data twin is compared to digital models of the clinical picture, which are optimised with the relevant studies and latest scientific findings. The computer should then support doctors with personalised treatment recommen- dations for cancer patients. ‘The final decision on treatment will obviously continue to be made joint- ly by patients and doctors,’ Neumuth points out. It is also envisaged that a patient- data explorer will link patient data from radiological images and med- ical reports via web technology, and that it will integrate molecular- genetic tumour information into the decision-making process, or calcu- late patient-specific therapy profiles for surgery and radio or chemother- Professor Thomas Neumuth is an engineer and IT specialist. His research focuses on model-based medicine, intel- ligent biomedical technology, and medi- cal IT systems. Born in Leipzig, he is the technical director of the Innovation Centre Computer Assisted Surgery (ICCAS) and heads the ICCAS Research Department for Model-based Medicine. His work on intel- ligent medical IT systems was chosen as a reference project for the Digital Summit 2017 by the Federal Ministry of Education and Research and confirms the position of the ICCAS as one of the leading research centres in Germany. apy. ‘Different types of information contained in the digital twin should be directly linked and analysed by AI,’ Neumuth adds. Many developments and tests are still needed to ensure that this and other technologies in the field of personalised cancer medicine can be directly integrated into clinical routine. ‘This will take three to five years,’ he estimates. ‘The objective is to create a sci- entific and methodological basis for personalised cancer treatment assisted by AI. In the ideal case, this means that a patient will receive personalised treatment based on the latest scientific findings, which takes into account the patient’s personal situation and specific needs, with everything being transparent and explained in an understandable way. We’ve Got Your Patients’ Heart Condition Covered. Remotely. BIOTRONIK Home Monitoring® enables safe replacements of in-ofﬁ ce follow-ups, continuous monitoring of patients’ clinical status, and automatically notiﬁ es physicians of trends and critical health changes anytime, anywhere. www.biotronik.com/homemonitoring * Complete labeling descriptions can be found in the technical Home Monitoring Service Center manual. TRUST: Varma N et al. Circulation. 2010; 122(4). RM-ALONE: Garcia-Fernandez FJ et al. European Heart Journal. 2019; 40(23). IN-TIME: Hindricks G et al. The Lancet. 2014; 384(9943). Report: Katrin Schreiter Siri and Alexa are leading the way: virtual assistants meet many daily needs. Soon, similarly programed software and a ‘digital patient twin’, will be launched into the medical world – both IT applications based on Artificial Intelligence (AI). The virtual medical assistant and digital patient twin are two key aspects of a research project ‘Models for Personalised Medicine’. Scientists at the Innovation Centre for Computer Assisted Surgery (ICCAS) in the Medical Faculty at Leipzig University aim to use these tools to improve the treatment of cancer patients. The project has received funding of around €5.1 million from the Federal Ministry of Education and Research and is being implemented with the help of companies in the Free State of Saxony, in eastern Germany. based on this information and make a joint decision,’ he explains. Different technologies have been designed with various pilot applica- tions: ‘The objective is to support the medical treatment of cancer patients with the help of IT,’ explains Professor Thomas Neumuth, who heads the project at ICCAS, and is also the Deputy Director of the centre. Targets include, for instance, patients with head/neck tumours. IT support starts with the tumour board, i.e. interdisciplinary discus- sion between surgeons, radiolo- gists, radiotherapists or patholo- gists. ‘Experts from different medi- cal disciplines discuss the medical condition of the respective patient,’ Neumuth explains. ‘It’s a type of briefing where all information relevant to the decision- making process is evaluated. The experts discuss treatment options In the future, the virtual assistant is to be present at these discussions as well. ‘This means we won’t lose any information,’ he points out. However, among programming chal- lenges will be the different volumes of sound and different positions of those who are talking in the room, which must be detected and accounted for. ‘Unclear pronunciation or strong accents should also not impact on word recognition.’ In contrast to conventional software, language recognition used in the context of medicine must be programmed for the specialist terminology and must also adhere to the strictest guide- lines on confidentiality. The Leipzig-based scientists have another vision: the so-called digital twin. This is an organised collection Malta: Moira Mizzi Spain: Mélisande Rouger, Eduardo de la Sota The Netherlands: Madeleine van de Wouw USA: Cynthia E. Keen, i.t. 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1 2 R A D I O LO G Y SPECIAL REPORT: The long-term impact of COVID-19 On the rise: Internal and external radiology The coronavirus pandemic – an international tragedy – created unprecedented upheaval and challenges within health systems, economies, and society. In hospitals, new ways of working had to evolve. Social distancing led to virtual consultations and teleradiology has found an added dimension, with its success, practicality, and effectiveness likely to see more widespread future use. Mark Nicholls asked three radi- ologists about the relevance of teleradiology during the epidemic, and what the future holds. Evidence collected during the SARS- CoV-2 pandemic by a team from the University of Tennessee, USA, clear- ly showed changing patterns in the use of teleradiology. Dr Mohammed Quraishi, Assistant Professor of Radiology, Section Chief of Body Imaging and Informatics Director at the University of Tennessee Medical Center, believes the term “teleradiol- ogy” needs disambiguation. ‘Often it brings to mind a radiologist far removed geographically, perhaps in a different country, reading for multiple hospitals with limited rap- port with any specific hospital,’ he said. ‘I would term this “external teleradiology”, because the radiolo- gist is external to the local group. It’s important to differentiate this from “internal teleradiology” where a radiologist, employed by the prac- tice, reads remotely.’ In the USA, practices during the pandemic increased internal telera- diology, and significantly decreased external teleradiology. ‘The reason seems two-fold,’ Quraishi surmised. ‘First, removing radiologists from the hospital makes sense when try- ing to mitigate the risk of contract- ing SARS-CoV-2 and, second, the increase in internal teleradiology – as opposed to external teleradiol- ogy – was almost certainly due to the drastic decrease in case volume.’ Whilst, traditionally, internal and external teleradiology have been used for on-call and overnight shifts for emergency radiology cases, day- time shifts during the pandemic were transferred to internal telera- diology – bringing off-site reading into the daily fold to help decrease radiologist exposure to potential SARS-CoV-2 infection, and allowing radiologists to work at home. The increased use of internal tel- eradiology was seen throughout the USA – particularly in the northeast, where the pandemic had preva- lence. To gauge changing teleradiology use, the group queried 290 loca- tions, representing a geographically diverse cross section of institutions. They found an overall jump in the proportion of sites installing home workstations (65.2%) and switching normal daytime shifts to internal tel- eradiology (73.6%). Around 56% of respondents said they saw enough benefit from the experience that they plan to continue similar work- flows post-COVID. 64.8% Specifically, reported decreased stress levels, and 96% found improved or no change in turnaround times, a position Quraishi echoed from his personal experience. ‘I found internal tel- eradiology less stressful, with an overall increase in productivity,’ he said. ‘Radiologists also reported less interruptions at home allowing them to focus on interpreting studies.’ He believes the pandemic will see a change of emphasis in the use of teleradiology, with practices re- evaluating teleradiology with new business models, services and work- flows, such as second opinion reads or even practices sending out stud- ies for subspecialty interpretations. Teleradiology to fight burnout problems Given increased evidence of radiolo- gist burnout and demands for bet- ter work/life balance, teleradiology might offer a solution. ‘According to our survey, the majority of groups plan to incorporate internal teleradi- ology into the post-pandemic work- flow. I predict internal teleradiology will rise across the country and, as groups get comfortable with that, there will likely be spill over into No compression. No superimposition. JUST GREAT IMAGING Visit us @ECR Virtual or www.ab-ct.com external teleradiology.’ Former NHS consultant Dr Stephen Davies, now Medical Director of the Medica Group, a business providing teleradiology services to the NHS, said: ‘Working from home using teleradiology has allowed radiology teams to work “in hospital” and out of hospital on rotation and increase opportunity for social distancing.’ Medica has facilitated “pass through” home reporting for radi- ologists to undertake their NHS ses- sional work using Medica’s existing image transmission and reporting. ‘The culture shift towards using technology to enable high-quality home working has risen during the COVID-19 crisis,’ he pointed out. Teleradiology has been used across the scope of diagnostic imag- ing, from emergency reporting – stroke and COVID chest X-rays – to elective imaging, and geographically this has been ‘without boundaries and is widespread’. Foreseeing a long-term growth ‘Teleradiology has been on a long- term growth trajectory and this will continue,’ Davies predicted. ‘COVID has increased the understanding of working from home. Teleradiology providers deliver a scalable, flexible quality assured reporting service which can respond to geography, reporting demand, time constraints and subspecialty constraints.’ He believes post-crisis teleradiolo- gy will become a bigger part of daily work routine with radiology servic- es finding a new balance between “in house” face-to-face radiology and protected and uninterrupted tel- eradiology home working. However, Davies has noted a downturn in vol- umes for all teleradiology services during the crisis, primarily due to a fall in elective work and emergency cases during lockdown, although, as restrictions ease, elective imaging services are increasing. Yet over the last decade, Dr Davies said teleradiology has been growing and is part of service provision for more than 90% of the NHS, with the delivery technology becoming ever-more sophisticated. That now sees the Medica Group offering a round-the-clock service across 90 UK hospitals. ‘The more experienced users of teleradiology have integrated the provision into their service in a seamless fashion. I expect this trend to continue and increase,’ he added. Key lessons have been learned in teleradiology use during the epi- demic, primarily from the NHS, rather than teleradiology companies – particularly ‘successful teleradiol- ogy replicating NHS office radiology requires more than simple deploy- ment of a workstation over simple domestic broadband. ‘Teleradiology,’ he predicts, ‘will continue to become more sophis- ticated with increasingly advanced operational delivery and image review, both supported by artifi- cial intelligence. Its penetration will increase into the provision of radiol- ogy reporting both emergency and elective work and will also use its platform and operational expertise to deliver emerging digital telepa- thology.’ With the Basel area a COVID- 19 hotspot in Switzerland, the Department of Radiology at the University Hospital Basel provided support via its teleradiology capa- bility. As cases rose in March, the unit – which delivers regular teleradiol- ogy services to local and regional hospitals at night and weekends – introduced a structured CT report- ing template for COVID-19 cases that included quantification of lung opacifications. ‘Around the peak of new infections in Switzerland at the end of March,’ said Dr Thomas Weikert, resident at the department, ‘we saw increasing numbers of CTs performed with the question of COVID-19 associated pulmonary infiltrates rising by +17% a day. ‘If that continued, we would have been in serious trouble very quickly. Luckily, the curve flattened during April as rigid public health meas- ures taken by the Swiss authorities brought the number of new infec- tions down. We were also develop- ing automated quantification pipe- lines to prepare for the situation where it was not possible to con- duct all the analyses manually.’ For COVID cases, lung segmenta- tion was conducted and via density thresholding, the percentage of lung tissue affected by infiltrates was established. ‘This is very useful for clinicians especially when it comes to follow-up. It is about quantifying COVID-related changes.’ The unit (which also runs an inter- national expert teleradiology read- ing program to provide structured reporting on Idiopathic Pulmonary Fibrosis (IPF) cases, which allows hospitals in Central Eastern Europe and Asia to send high-resolution chest CTs of suspected IPF to the university hospital), has continued to provide structured COVID-19 reports to local/regional partner hospitals via teleradiology. The value of teleradiology during the pandemic has been apparent and the Basel department moni- tored its growth during this period Dr Mohammed I Quraishi is Assistant Professor of Radiology, Section Chief of Body Imaging and Informatics Director at the University of Tennessee. He research- es data analytics and medicine, working towards ultimately improving patient care through advancing healthcare effi- ciency, diagnostic accuracy, cost-savings, and mitigation of physician burn-out. Dr Stephen Davies is Medical Director of the Medica Group and Fulltime Executive Director. A former NHS radiolo- gist, with more than 25 years’ experience as a consultant radiologist within the NHS, he is also a Past President of the British Institute of Radiology. Dr Thomas Weikert is a resident in the Department of Radiology at University Hospital Basel, Switzerland, where he researches translation of digital solutions in medicine and is involved in an evalua- tion of the IPF teleradiology program. with an internal RIS/PACS crawling tool, allowing them to identify all exams with COVID-19 related clini- cal questions. in ‘Teleradiology for COVID-19 cases can prove beneficial in three respects. First,’ Weikert continued, ‘by promoting structured report- ing, including quantification of pul- monary changes; second, should regional hotspots arise the future, overwhelming capacities of the regional health service provid- ers, teleradiology could share the diagnostic workload with radiology departments in less affected areas; third, by automatically analysing cases from many regions, it could be part of a regional outbreak early warning system. If many exams are diagnosed with COVID-19-suspected pulmonary changes, a warning sig- nal could be sent to the authorities. ‘I think, in a broader way, tel- emedicine, which includes teleradi- ology and provision of services of other specialties, will get a profound boost by this, because there are many people who used telemedi- cine for the first time and I think they will continue to use that.’ Consequently, Weikert expects the role of telemedicine and teleradiol- ogy to rise independently of the current public health crisis. EUROPEAN HOSPITAL Vol 29 Issue 2/20
R A D I O LO G Y 1 3 Physiopathological hypothesis needs validation on post-mortem studies We need a global view of COVID-19 Anand Devaraj is Professor of Practice in Thoracic Imaging at Imperial College London’s National Heart and Lung Institute and a consultant thoracic radiologist at the Royal Brompton Hospital in London, UK. Mickaël Ohana is a professor of radi- ology at the University of Strasbourg and radiologist at Strasbourg University Hospital in France. He specialises in non- invasive cardiovascular and chest imaging. Myriam Edjlali-Goujon is a neuroradiol- ogist at Hôpital Raymond-Poincaré, Paris- Saclay University, France. There are major complications from COVID-19 – ARDS, pulmonary embolism and neurological – that imaging can help detect, manage and/or follow up in the long term, radiologists from France and the UK explained during a recent ESR Connect session. Fig. 1 Fig 1: Good evolution of a COVID-19, with almost normal initial chest CT at D3, extensive ground glass opacities (GGO) at D9 and almost complete resolution with limited residual GGO at six weeks Fig. 2 Pulmonary embolism – An early paper, from Italy, on pulmonary embolism and COVID-19 questioned whether there was a random associa- tion between the two. Clinicians now know from a wealth of evidence that it is not random, and there is a strong association between pulmo- nary embolism, indeed all thrombotic phenomena, and COVID-19, accord- ing to Anand Devaraj, a professor of thoracic imaging at Imperial College London’s National Heart and Lung Institute. ‘A number of publications have shown that the rate of pulmo- nary embolism in patients undergo- ing CTPA admitted with COVID-19 is around 30%,’ he said. ‘There is also evidence to suggest that this is not just a question of pulmonary embolism, but of hypercoagulation in COVID-19 pneumonia.’ The parameters that suggest this phenomenon include, for example, very high D-dimer levels in patients with COVID-19. ‘The pulmonary emboli that we see in Covid-19 pneumonia are often segmental or subsegmental. But a significant minority of patients also have quite severe clot burden, more proximally. Some patients also have very elevated right heart pressures and right heart dysfunction.’ The precise treatment and pre- vention of pulmonary embolism in these patients is a complex deci- sion for clinicians based on a num- ber of factors, taking into account hypercoagulability and the risks of haemorrhage. But there are reports of thrombolysis being effective in patients with large clot burdens and very high D-dimers, according to Devaraj. ‘In terms of parenchymal signs, there have been a number of reports describing the observation of dilated subsegmental vessels in patients with COVID-19 – known as vascular thickening, or vascular congestion – seen in up to 89% of Fig 2: Moderate GGO and alveolar consolidations on initial Chest CT at D7, evolving towards reticulations at D14 and with pattern of organising pneumonia and traction bronchiolectasis at three weeks. Whether these lesions will completely resolve or not at further follow-up is still unknown patients. We have also seen this in our patients with severe respiratory failure due to COVID-19.’ These dilated subsegmental ves- sels are peripheral and branching, mimicking tree-in-bud nodularity, but very much centred on the ves- sel. The aetiology of these opaci- ties is uncertain, but they could reflect thrombotic microangiopathy,’ Devaraj noted. Some recent autopsy data has also pointed towards thrombi within the peripheral vasculature being present as a common phenomenon. The thrombotic hypercoagulable state that radiologists see on imaging in COVID-19 is not just pulmonary embolism; there are also reports of Continued on page 14 Report: Mélisande Rouger ARDS – Acute respiratory distress syndrome (ARDS) is the most dread- ed complication and the number one morbidity in COVID-19 patients. The incidence was up to 30% of patients in initial reports. In Strasbourg University Hospital, at epidemic peak, there was an 8% rate of admis- sion to ICU directly after ED admis- sion because of ARDS, according to Mickaël Ohana, a local professor of radiology who specialises in non- invasive cardiovascular and chest imaging. ARDS diagnosis is not based solely on imaging, but, in line with Berlin criteria, is based on acute hypoxemia plus bilateral radiographic opacities, through chest X-ray or chest CT. ‘The problem is not diagnosis – it is pre- diction and follow-up,’ Ohana said. Prediction – Few papers have tried to score the risk of ARDS from an initial chest CT of a COVID-19 patient, based on either quantitative or visual assessment. But these types of semi-quantitative scores are not highly reproducible, not standard- ised, and are time-consuming. ‘I would advise simply using the ESR/ESTI visual scale, which is based on the extension of the lesions over the lung parenchyma, and then clas- sifying in five different levels. This is a very simple visual quantification, which can be done readily for any patient. We found that, in about the first 200 patients, if you have less than 25% lung involvement, the risk of going to ICU or dying is about 18%. If you have more than 25%, the risk is much higher,’ Ohana said. The risk of fibrosis is also a central concern in these patients. Clinicians know from other types of ARDS – not related to COVID-19 – that 50-75% of patients after ARDS are at risk of fibrosis, with varying severity, whether with radiological lesions or clinical lesions. ‘If you have fibrosis on imaging, and even if it is subclinical, it is a risk marker for mortality. ‘The question that remains is regarding the risk of fibrosis in COVID-19 survivors, after ARDS. We currently do not know this risk because we have not had enough time after the initial ICU stay,’ he explained. There are different potential evo- lutions, from ground-glass opacities to crazy paving to consolidation. The questions radiologists must ask themselves are: How can they screen these patients to see which are lead- ing to recovery and which are lead- ing to fibrosis? And when should they follow up with these patients? ‘Based on experience with other types of ARDS, we think that less than three months is probably too early for follow-up CT for patients leaving the ICU. And when doing the follow-up scan, we try to optimise the acquisition protocol so as not to have over-radiation,’ he concluded. www.healthcare-in-europe.com
1 4 R A D I O LO G Y Epidemic: POCUS hailed as the initial screening tool Ultrasound confirms frontline value Ultrasound could become the prime modality in emergency set- tings for tracking disease progression in Covid-19 patients, Mark Nicholls reports. sound fellowship director for the Department of Emergency Medicine and the Director of Point-of-Care Ultrasound Education for Yale School of Medicine, said the key seasons ultrasound has emerged as a first liner in emergency settings to diagnose Covid-19 is largely due to avoidance of exposure and trans- mission of virus particles; disinfec- tion; and preservation of PPE. ‘Emergency personnel are often the first to see, examine, and talk to a patient,’ she said. ‘As we need to see the patient anyway, it makes sense if we perform as complete an evaluation as possible to avoid others needing to come into con- tact with that patient. This includes obtaining swabs, lab work and imaging. If the emergency provider can perform diagnostic imaging at the same time as evaluating the patient, then this prevents others – transporters, cardiologists, radiolo- gists and technicians – from needing to come into close contact with the patient.’ Cleaning and disinfection A second critical area is cleaning and disinfection, particularly where CT suites are fixed spaces that would be shared by COVID and non-COVID patients. ‘Many hospitals do not have enough machines, or the infrastruc- ture to create cohorted radiology spaces. So, a CT performed on a Covid-positive patient would shut down that machine for up to an hour, so that it, and the surrounding Depicting fluid in the interstitial space that surrounds alveoli with severity causing confluent B lines We need a global view of Covid-19 influenza A virus, in which radiolo- gists see T2/FLAIR hyper intensity within bilateral thalami and temporal lobes, evidence of haemorrhage and enhancing lesions on post-gadolini- um sequences. Cytokine storms – ‘Acute haemor- rhagic necrotising encephalopathy has therefore been related to intra- cranial cytokine storms. This is inter- esting because cytokine storm syn- Continued from page 13 drome has been recently reported in COVID-19 patients and may play a role in the development of those types of encephalopathy,’ Edjlali- Goujon noted. Another example of the polymor- phism of the different secondary diseases related to COVID-19 is the aspect of the cytotoxic lesion of the corpus callosum (CLOCC) in a COVID-19-positive patient. There is a presence of an ovoid region of Patient with Covid-19 pneumonia: CT shows left lower lobe pulmonary emboli. Dependent dense opacification and anterior ground glass opacities are present in keeping with ARDS. Note also serpiginous dilated peripheral vessels that are frequently seen in patients with severe disease While chest CT has held a key diag- nostic role thus far, many experts now advocate the benefits of ultra- sound within the context of the coronavirus epidemic. Dr Rachel Liu, who recently led a high-profile panel discussion with experts from the USA and areas of Europe with high incidence of COVID-19, dis- cussed the advantages offered by ultrasound, and particularly point- of-care ultrasound (POCUS). Liu believes the role of POCUS and traditional ultrasound has changed with the length of the pan- demic, and will continue to evolve. ‘In the early stages of the crisis, lung ultrasound was used diagnostically in conjunction with COVID swab testing, because swab testing could be unreliable,’ she explained. ‘It may have also been used to aid physi- cians in selecting the patients most eligible for swab testing.’ However, as the pandemic evolved, and with better testing available, the value of ultrasound as a portable, flexible and time- efficient modality increased, with its value becoming more apparent in categorising mild, moderate or severe disease, discharge decision- making, and baseline monitoring of cardiac function and lung involve- ment for patients admitted to the hospital, for example. Liu, who is the emergency ultra- increased rates of ischaemic stroke, myocardial infarction, and aortic and cardiac thrombus, Devaraj explained. complications – Neurological COVID-19 can also be responsi- ble for neurological complications, according to Myriam Edjlali-Goujon, a neuroradiologist at Hôpital Raymond-Poincaré, Paris-Saclay University. ‘There are two physio- pathological mechanisms suggest- ed to explain these complications. The first is using the spread from mechanoreceptors in the lung via a synapse-connected route to the med- ullary cardiorespiratory centre; the second is entering the brain primar- ily via the olfactory bulb,’ she said. This second hypothesis has been validated on other types of SARS- CoV virus and was published more than ten years ago. The hypothesis is sustained by clinical symptoms, such as anosmia, which is present in more than 80% of patients with mild-to-moderate forms of COVID- 19. ‘Anosmia is becoming a very spe- cific symptom of COVID-19, espe- cially when reported without nasal obstruction or rhinorrhea. It is also sustained by imaging publications showing abnormal T2 signals of olfactory bulbs,’ she explained. One of the first articles on brain lesions, from March 2020, described acute haemorrhagic necrotising encephalopathy, a well-known post- viral complication, especially of the space, can be cleaned. Contrast that with a portable ultrasound machine which can be cleaned and disin- fected in a matter of minutes, with a dwell time of only 2-3 minutes between cleaning and use on the next patient. ‘Often, and particularly if a site also uses pocket or handheld devic- es, there is more than one machine in the emergency department. That means that there is a possibility of dedicating machines solely for use in COVID spaces, while also having machines available for non-COVID spaces.’ Thirdly, as fewer people need to come into contact with the patient, less PPE is used, which helps con- serve PPE in a time of worldwide shortage. Liu said ultrasound offers advan- tages over CT, and other modali- ties, in the coronavirus context and points to preliminary literature in the Covid time period, as well as previous imaging literature on Acute Respiratory Distress Syndrome (ARDS), suggesting that lung ultra- sound approaches share similar test characteristics with CT. With all the advantages of isola- tion from others, speed of operation and cleaning, Liu concluded POCUS to be overall ‘the most expedient modality’. Portable chest X-ray, she added, does not have test character- istics that match CT, and findings on both CT and lung ultrasound can be seen before they appear on X-ray, though she acknowledged that all imaging has limitations. Five reasons for diagnostic ultrasound The 10-strong expert panel’s discus- sion report highlighted five reasons why diagnostic ultrasound should be considered for imaging in suspected COVID infection cases: both a nor- mal and abnormal lung ultrasound may provide key clinical insights; lung ultrasound may help rule out other pulmonary diseases; cardiac ultrasound could detect heart prob- lems caused, or exacerbated, by COVID-19; ultrasound may benefit critically ill patients needing periph- eral or central venous access; POCUS can reduce numbers of healthcare workers exposed while supplying immediate diagnostic information. the splenium of the corpus callosum with increased T2/FLAIR signal, high DWI diffusion, with restricted ADC values and reduced T1 signal on post-gadolinium injection. CLOCC lesions are known to be secondary to an underlying evolving cause and the corpus callosum is very sensitive to markedly increased levels of cytokines. ‘Both acute haemorrhagic necrotising encepha- lopathy and CLOCC therefore sug- gest specific complications related to maladaptive cytokine profile,’ she explained. Different retrospective studies have been published reporting the preva- lence of neurological complications. One from Strasbourg and another from Wuhan show that neurological manifestations may occur in 40-70% of hospitalised COVID-19 patients. In terms of neurological signs, agi- tation was very frequent; and in terms of brain MRI, leptomeningeal enhancements, perfusion abnormali- ties and cerebral ischaemic stroke have been noticed. ‘Most frequently, when a lumbar puncture was done, the RT-PCR for SARS-CoV-2 in CSF was negative. Meanwhile, new reports of rarer complications are emerging, such as Guillain-Barré syndrome, Myelitis, Miller-Fisher syndrome and enceph- alitis,’ she added. Besides, a study published in the New England Journal of Medicine showed an association between COVID-19 and increased incidence of stroke, because of pro-inflam- matory and prothrombotic disease, with emergent large vessel occlusion detected as an early stage or even presenting symptom. However, the studies show that the number of stroke patients decreased within the COVID-19 pandemic, Edjlali-Goujon pointed out. ‘In France, there is a 21% decrease of mechanical thrombec- tomy during the quarantine. But this could be questioned too, because of the significant increase in care delays,’ she said. Anosmia and other abnormalities of the olfactory bulb are usually linked to mild-to-moderate symp- toms, often isolated, without other neurological deficits and most often without any other abnormalities on MRI. Apart from anosmia, there are more severe complications, such as maladaptive cytokine profile, leptomeningitis and encephalitis, and hypoxic and thromboembolic lesions. In the second phase of the disease, inflammatory lesions can appear and radiologists have to watch for these very carefully. ‘There is a need for a global view on the disease,’ Edjlali-Goujon concluded, ‘and an epidemiological follow-up; and it is important for the physiopathological hypothesis to be validated on post-mortem studies.’ EUROPEAN HOSPITAL Vol 29 Issue 2/20
R A D I O LO G Y 1 5 A clean slate to design imaging investigations in an ideal world Out of adversity comes opportunity The critical role of radiographers in the coronavirus epidemic was high- lighted in the final episode of the ESR Connect series of webcasts, ‘Radiology fighting Covid-19’. Three European speakers in the ses- sion ‘Radiologists & Radiographers: Lessons learned from the pandemic’ (chaired by Helmut Prosch, Professor of Radiology at the Medical University Vienna), discussed their coronavirus experiences and how the pandemic might impact on radiology depart- ments in the future – particularly as they work towards regaining routine clinical practice. and Dr Nick Woznitza, senior lectur- er and radiographer at Homerton University Hospital the Canterbury Christ Church University in the UK, detailed the British Society of Thoracic Imaging’s Radiology Decision Support Tool for suspect- ed COVID-19 and the route such patients take. Having been heavily involved in coronavirus care, Woznitza shared his experience in his presentation ‘Covid-19 – Departmental Planning & Radiographer Interpretation’, sum- marising how radiographers keep patients and colleagues safe and examining how imaging departments can begin to plan for the post- pandemic. A phased reinstatement of other healthcare services according to clini- cal need, with pre-screening of out- patients for symptoms, remain key considerations, with dual working, where possible, to help reduce cross contamination, decontamination of equipment/rooms, and streaming Dr Nick Woznitza is senior lecturer and radiographer at Homerton University Hospital and the Canterbury Christ Church University in the UK. Radiographer Dr Moreno Zanardo is a research fellow at the radiology department of the University of Milan’s IRCCS Policlinico San Donato; and Dr Lukas Ebner is the leading tho- racic radiologist at the Inselspital Berne, Switzerland. out, with free psychological support and a weekly survey to investigate potential stress, are also crucial. Use of mobile X-ray equipment was a valuable step, with the Bergamo region, at the epicentre of the Italian outbreak, performing more than 500 chest X-rays in nursing homes or patients’ houses. ‘We believe the costs of this approach are lower than bringing the patient to the radiology depart- ment,’ Zanardo said. ‘It also can be useful for reducing contamination and stress for the patient.’ Radiology dose is low; shielding is not mandatory, because lead aprons can be a transmission risk, he point- ed out. Now work must be rescheduled to move towards normal practice but, he noted, there are 1.2 million missed mammographs in Italy with asymptomatic screening mammog- raphy on hold until community risk is minimal. Dr Lukas Ebner, leading thoracic radiologist at the Inselspital Berne, Switzerland, gave an overview of the benefits and disadvantages of CT ver- sus radiography for imaging Covid- 19 patients, taking into consideration local healthcare policies, resources and management at the point of care. CT, Woznitza pointed out, is a sen- sitive tool, particularly in the early stage of Covid-19 and in patients with no or mild symptoms and in the identification of complications such as pulmonary embolism, whilst chest X-ray is not so sensitive for early findings but with moderate, more advanced or severe symptoms, the ‘sensitivity increases substantially’, the radiologist adds.. Other factors to consider are the logistics of having to send patients for a CT, the resources, and hygiene measures. Ebner explained the triaging pro- cess at his hospital, which has a fast- track solution offering a turnaround time of two hours to rapidly identify patients who need hospital care and those who can self-isolate at home. He also highlighted examples of patients seen during the crisis at various stages of their disease progression and follow-up in each modality, along with useful resources helpful to radiologists and radiog- raphers during the current epidem- ic. These included, ‘Covid-19 and the radiology department’ from the European Society of Radiology and the European Society of Thoracis Imaging; and ‘The Role of Chest Imaging in Patient Management during the Covid-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society’. into suspected/non-suspected Covid area. ‘The key question,’ said Woznitza, ‘is how we start managing the patient flow in the department and are we “reinstating, or reinventing” health- care?’ One approach in England, he added, has been to adopt a regional approach, using different hospital sites for suspected or non-suspected coronavirus cases. Radiographers were ‘at the fore- front of the crisis’, he added, playing an essential role in managing the pandemic and triage of Covid-19 cases, emphasising the importance of giving radiographers the right education and support to perform effectively under challenging circum- stances. ‘Radiography triage will add value; radiographers are often the first healthcare professionals to see a diagnostic image; they have a key role as frontline, patient-facing staff. They deliver good patient manage- ment, reduce transmission risk and lead to reports produced as soon as possible.’ In looking at the pathway to go back to normal, he said: ‘We do not need to reinstate services; we need to reimagine services; there is the opportunity for a clean slate and start designing investigations along the lines of how we would design them in an ideal world, rather than automatically do everything the same as we have always done. Out of adversity,comes opportunity.’ imaging Radiographer Dr Moreno Zanardo, currently a research fellow in the radi- ology department at the University of Milan’s IRCCS Policlinico San Donato, outlined how workflows can be maintained under difficult con- ditions, and key areas of minimis- ing Covid-19 infection from patients; training radiographers in protecting themselves; maintaining precautions in the post-pandemic setting; and the role of mobile equipment. Covering his experiences against a backdrop of limited clinical activity, PPE shortages, and steps towards the transition back to routine practice, Woznitza outlined how his institute minimised the risk of infections using isolated imaging rooms for suspected or confirmed Covid-19 patients; dedi- cated pathways to perform radio- logical examinations; centralised PPE supplies and appropriate equipment sanitisation scheduling to limit con- tamination. Sharing information – such as the WHO document on how to wear PPE correctly and involvement with an international group to train radiog- raphers in the context of Covid-19 – and considering the mental health of radiographers and preventing burn- At Yale School of Medicine, in Connecticut, Dr Rachel Liu is the emer- gency ultrasound fellowship director at the Department of Emergency Medicine and the Director of Point-of-Care Ultrasound Education. Her research inter- ests include the use of point-of-care echo to guide performance of cardiopulmonary resuscitation, integration of new tech- nologies into hospital and educational infrastructure, and system-wide devel- opment of point of care ultrasound pro- grams. She has held all major leadership positions within the ultrasound sections of the American Emergency Medicine societies, notably the American College of Emergency Physicians, for whom she authored guidelines for implementation of handheld ultrasound technologies. ‘Much is still being developed,’ Liu concluded, ‘but I think the role of point-of-care ultrasound as an initial screening tool has become more established. Prior publications on ultrasound in H1N1 and ebola patient care already suggested this, but this pandemic has really made this concept hit home. ‘This can translate to imaging con- siderations throughout the length of the pandemic, as well as in future pandemics. Because of this, POCUS should be firmly established in future emergency preparedness and global public health or public policy plans.’ Research is underway in developing severity scores based on ultrasound findings, Liu added, and this may help in the second or third waves of COVID, as well as in future pandemics. Orders for mobile X-ray solutions made by OR Technology, in Germany, have multiplied several times since the Coronavirus COVID-19 global epidemic began, with orders from Vietnam, Luxembourg, Portugal, South Africa, Ghana and Trinidad & Tobago and many other countries. ‘With this X-ray system, the challeng- es of the pandemic can be mastered better,‘ confirmed Managing Director Bernd Oehm. ‘In a few seconds, excellent pulmonary images of a suspected COVID-19 patient can be obtained. Our lightweight complete solution Amadeo M-DR mini, for example, is suitable for outdoor use as well as bedside imaging in hospi- tals or nursing homes.’ This advanced all-in-one system includes all necessary components, such as X-ray detector, X-ray gen- erator and image processing station. The user is supported by a practical X-ray assistant. ‘The Amadeo M-DR mini enables wireless digital X-rays of the entire body trunk,’ the manu- facturer adds. ‘The X-ray solution is brought directly to the patient, preventing www.healthcare-in-europe.com Mobile and portable X-ray machines circle the globe International sales soar costs,’ OR Technology points out. ‘In the case of a temporary power inter- ruption, the device can still be used to take X-ray images. ‘The compact X-ray unit is simple and easy to move,’ OR adds. ‘Folded up, it’s easy to transport and even fits into a station wagon. Steps and uneven terrain are no obstacle. The wheels allow easy 360-degree rota- tion even when folded, which makes it much easier to handle in confined spaces such as elevators. Details: firstname.lastname@example.org long waiting times in crowded hos- pitals. The unit can be set up and ready for use in less than two min- utes. Transport and operation can be carried out by one person. The inte- grated diagnostic software ensures a worldwide and fast exchange of information via cloud or e-mail. This saves a lot of time and transport Mobile X-ray machine Amadeo M mini for ambulatory and in-patient care
1 6 R A D I O LO G Y Radiographers on the front line Prioritising equipment hygiene The pandemic has put extra pressure on radiology services and radiographers are particularly at risk of catching and spreading the disease. Strict cleaning and disinfection protocols must be followed, accord- ing to Pablo Valdés Solís, President of the Spanish Society of Radiology (SERAM), who recently published new guidelines on how to protect staff and patients. Report: Mélisande Rouger Ever since the first COVID-19 cases were reported in January, radiology workflow changed entirely and the focus fell on an essential, yet not vis- ible, part of the department’s work: equipment hygiene. ‘Increasing awareness of how to clean and disinfect devices adequately is cru- cial not only to protect our staff, but also not to spread the disease to patients and colleagues during radiology examinations,’ cautioned radiologist and President of SERAM, Pablo Valdés Solis. A new resource to support radiographers: basic con- cepts of Covid-19 The SERAM published guidelines last April to help radiographers keep staff and patients safe during the pandemic, because the Spanish radiographer doesn’t include the necessary microbiology background to understand how the disease spreads. training ‘Radiographers don’t receive that much training in virology. But if you understand what the disease is and how it spreads, you will better understand what needs to be done,’ Valdés said. The document reviews basic con- cepts of COVID-19 and suggests a detailed list of measures that must be taken in radiology departments to prevent its spread during radio- logical examinations. It has been observed that the virus can survive as long as three days on stainless steel and plastic. Staff must therefore not only wash their hands before, during and after an examination, but also clean and disinfect all the equipment they have used with a patient. Keeping equipment intact means that all surfaces that will be in direct contact with a patient should be covered as much as possible with impermeable material that can be discarded after each examination. For example, in portable X-ray, radiographers should cover the shell with a plastic bag. In ultrasound, it is preferable to use a sleeve to cover the probe, but not absolutely neces- sary if the patient’s skin is clean. ‘If you have sleeves, you should cover the equipment and especially the console area, to facilitate poste- rior disinfection and minimise dam- age risk to the equipment,’ Valdés pointed out.. The equipment can be washed directly with soap and water or specific cleansers. Powerful cleansers, organic disinfectants, alcohol and dissolvent should never be used as they may damage the surface. Disinfection is another key step of the cleaning routine, especially during the pandemic. The aim is to diminish the microorganism load, assuming that some will remain in non-threatening levels. Disinfection can be classified into three levels. The so-called low level is the elimination of bacteria, fungus and some viruses by applying the product in the examination room and on the equipment surface for less than ten minutes. Intermediate-level disinfection consists of eliminating TB bacillus and most of the existing bacteria, viruses and fungus. High-level dis- infection is the complete elimina- tion of germs – except bacterial spores – and is traditionally used to decontaminate medical devices, such as endoscopes, anaesthetic material and other medical devices that have been in touch with a patient’s mucosa. Sterilisation will eliminate all microorganisms, including bacterial spores, from any surface in criti- cal material like endocavity probes, surgical material and non-reusable interventional material. The coronavirus is covered by a lipid layer and is therefore vulner- able to soap and traditional disin- fectants. For most medical equip- ment used in daily routine, low to intermediate disinfection is enough. Pablo Valdés Solís is Area Director of Costa del Sol Healthcare Agency in Marbella, Malaga, Spain, and the cur- rent President of the Spanish Society of Radiology (SERAM), and has over 25 years professional experience. His special interest lies in paediatric radiology and emergency radiology. For the past fifteen years, he has focused on management and quality. Special products are not neces- sary and the disinfectant solution can be applied for five minutes. For example, a solution made of 0.1% sodium hypochlorite (bleach), 62-71% ethanol or 0.5% hydrogene peroxyde can inactivate the virus in just a minute. The solution should not be applied directly though, but by using a gauze, compress or cloth that has been previously soaked. Different areas throughout the country need different protocols Hospitals across Spain are affected differently depending on the local incidence of the COVID-19 coro- navirus. Madrid has been the most impacted area, with 68,852 infected patients as of June 1, according to the Spanish Ministry of Health. The Spanish capital has derived COVID-19 patients to major insti- tutions like La Paz and Ramon y Cajal, and temporary structures like IFEMA, a conference centre that has become Spain’s largest hospital with 5,500 beds. By comparison, Andalusia has registered 12,679 infected patients, 134 of these in the past 14 days. Due to these differences, hospi- tals must themselves decide which hygiene protocols they need to fol- low. ‘We recommend establishing these rules together with the local preventive medicine experts. Taking care of the examination rooms and materials starts by adequate clean- ing, according to the hospital poli- cy,’ Valdés pointed out. Also important to bear in mind are the protocols recommended by equipment manufacturers, as some devices or components may be more sensitive, for instance ultra- sound probes and some areas in CT gantries. The unexpected positive consequences for simple X-ray exams Radiology is learning lessons from the pandemic, Valdés observed. ‘We’ve regained an excellent habit, which is to report on simple X-ray examinations. This is really some- thing we need to value more. Being able to study simple radiology is extremely important.’ Keeping equipment clean has also returned to centre stage. ‘Radiation and magnetic resonance safety have long been the focus of our preoc- cupations, but it’s very important to take care of the material as well,’ the SERAM President concluded. Infectious diseases are traditionally the concern of clinicians, but this pandemic has reminded us of how important hygiene is and that we all have a role to play.’ EUROPEAN HOSPITAL Vol 29 Issue 2/20
D I G I TA L PAT H O LO G Y 1 7 The need for modernisation Digital pathology: Luxury or necessity? The anatomical pathologist faces a crisis. Public and private labs suffer increasing caseloads, whilst pathol- ogist numbers diminish for various reasons, including greater cancer prevalence associated with aging populations as well as improved can- cer screening programs. Precision medicine typically involves more genetic testing and extensive use of immunohistochemistry to classify cancer and assess prognostic and predictive biomarkers. In clinical practice, a notable number of pathologists are nearing retirement, yet today’s diagnostic pathology training of young doctors is limited. Alternative: the optical microscope Recently, digitisation and digital pathology have become widely accepted due to advances in tech- nology and regulations. In essence, in digital pathology a scanner pro- duces a digital copy of the tradi- tional glass slide, to be stored in Decades ago, when digitisation entered radiology to produce digital images, film was no longer needed. The savings eased an initial reluc- tance among some groups, but not in pathology since elaboration of the glass slide is still required. This, coupled with concerns over increased turnaround times due to the added step of scanning, as well as the substantial initial investment needed to fully digitise a lab, help explain the slow rate of path dig- itisation. What’s in it for pathologists? Despite concerns, today’s digitisa- tion brings multiple advantages to pathologists and patients. Early digital pathology adopters report many benefits, including efficiency gains and better case allocation across digital pathology networks. The availability of a digital histol- ogy slide enables distant viewing and remote reporting, particularly appealing given demands imposed Artificial intelligence in pathology – friend or foe? Artificial intelligence (AI) tools, including deep learning algorithms, can be applied to a digital histol- ogy image to facilitate computer- assisted diagnosis, which forms the basis of computational pathology. The application of AI to pathology bears promise, including increased accuracy in immunomarker quantifi- cation, better sample screening and pathologist efficiency, with reduced mis-diagnoses. The discovery of new morpholog- ical predictors of disease outcome, invisible to the human eye but apparent to a computer, also sug- gests new diagnostic possibilities. The current capability to manage and analyse huge pathology image data, combined with more advanced techniques to simultaneously detect multiple molecules or antigens in situ, fosters a novel field of research. However, a prerequisite for com- putational pathology to fulfil its promises and become mainstream, a local or cloud-based server and viewed anywhere with a computer and internet connection. Current scanners provide high fidelity digital images thanks to high magnification (40x). Additionally, high throughput scanners, with a capacity of up to a thousand slides, are capable of fast, reliable operation with little human intervention, making possible unsu- pervised overnight operation and samples ready for review by pathol- ogists and trainees in early morning. Licensed but a slow uptake In 2017, the USA’s Food and Drug Administration (FDA) warranted the first license for the use of digital pathology for primary diagnosis in that country. Permission for in vitro diagnosis came sooner in Europe. Despite this, adoption of digital pathology has been slow for sev- eral possible reasons. A commonly mentioned barrier is pathologists’ concerns, such as digital images inferiority, or a slowdown in the sign-out process. by COVID-19. Multiple users can access digital images, regardless of location, enabling second opinions and consultations. Shipping and storing glass slides on site is obvi- ated. Digital rather than analogue archives are more manageable; prior cases are available quicker for compara- tive review. Early users report overall efficien- cy includes shorter reading times during diagnostic sign-out sessions, improved overall lab efficiency in the range of 20%, or more, after complete digital diagnosis, com- pared with analogue workflow. In addition, the improved intra- laboratory logistics (the technician time required to sort the hundreds of slides prepared every day in the typical lab, distributing them to the responsible pathologist, collat- ing them for tumour boards, and the added ease to manage consulta- tions, etc.) may add to the savings and lower the financial barriers for adoption. is the general adoption of digital pathology – because the develop- ment and training of AI algorithms requires vast amounts of carefully annotated digital data. Additionally, once algorithms have been devel- oped, they can only be applied in clinical routine use in labs that have successfully embraced digitization: by logic, AI tools cannot be applied to analogue glass slides. Some medical professionals fear that machines could work more rap- idly and accurately than a human. However, the whole point of com- puter assisted diagnosis and compu- tational pathology is to help pathol- ogists. In monetary terms Digital pathology efficiency gains can be translated into monetary terms. It is important to estimate how long before an initial invest- ment in lab digitisation show a return. A model proposed by the University of Leeds, in the UK, estimates that efficiency gains of www.healthcare-in-europe.com Dr Juan Antonio Retamero is an anatom- ical pathologist with extensive experience in the implementation and use of digital pathology for routine diagnosis. He played a key role in the adoption of digital pathol- ogy in a pioneering group of Spanish hos- pitals in 2016. He has shared those experi- ences internationally and supported many centres in adoption digital pathology adop- tion globally, including labs in the USA. Europe and Asia. He is a regular speaker at digital and computational events and an ardent advocate for modernisation of the profession. Retamero is also Consultant for Philips Digital and Computational Pathology. between 10-15% result in an amor- tisation of the initial investment after 1-2 years. Based on this model, efficiency gains of 20%, as reported by some users, would point towards an early amortisation of the initial cost outlay. How staff requirements change due to enhanced productivity in a fully digital lab needs analysis. Where pathologists are retiring and cannot be replaced, early digital pathology adopters report that, due to greater efficiency, a reduced pool of pathologists can absorb increas- ing caseloads. The differences in full- time equivalents (FTEs) of patholo- gists’ time to process the same case- load, when comparing those on the microscope, versus that same group of pathologists with better efficiency after digital transformation, show that the personnel savings from fewer FTEs needed are sufficient to amortise the initial investment after 2-3 years. Additionally, these FTEs savings, over five years – the typical life of a digital pathology system – do result in an additional lab profit over the fourth and fifth year, before additional expenditure is needed to renovate obsolete elements in the system. Therefore, the investment made efficiency gains that trans- late into a repayment of the initial amount around the second year and additional monetary gains for a fur- ther 2-3 years. Can I work remotely? A pillar of digital pathology is reli- ance on the creation of a digital twin of the glass slide, in a file accessed by anyone with the appro- priate credentials from anywhere with an internet connection and a PC. The images are typically stored in a server, usually integrated with- in the main hospital infrastructure. From here, the digital slides can be accessed remotely via a virtual private network (VPN), that cre- ates a secure access to the hospital IT system. The data transmission Falko Fend MD is Professor of Pathology and Chairman of the Institute of Pathology and Neuropathology and Reference Centre for Haematopathology at the Eberhard-Karls University in Tübingen, Germany. Following postgrad training in the Pathology and Internal Medicine Departments at Innsbruck University, in 1991 he became its staff pathologist. From 1997-1999, he was a research fellow at the Laboratory at the National Cancer Institute, NIH, Bethesda from 1997-1999, when he became Associate Professor of Pathology at the Institute of Pathology of the Technical University Munich, and later took on his current position at the University of Tübingen. His research focuses on the pathology and molecular genetics of malignant lymphomas and innovative molecular pathology. Fend is also a member of the execu- tive boards of the German Society of Pathology, the European Association of Haematopathology and served as Chairman of the European Bone Marrow Working Group. rate necessary for satisfactory view- ing – a bandwidth of 300 megabits per second (Mbps) – is sufficient to ensure optimal performance when loading, panning and zooming the image. Currently, the typical optic fibre bandwidth for domestic use offers three times that speed. Other important elements are the PC and monitor needed to view digital images. In 2017, the FDA warranted permission to the first digital pathology system for pri- mary diagnostic use in the USA. Part of the system is a PC with an Intel Xeon CPU E5-1620 v3 at 3.50- GHz processor, 16 GB RAM, and an NVIDIA Quadro K4200 graphic card. These hardware elements, as usually with IT components, cost significantly less now. The FDA monitor approved for primary diag- nosis is medical grade LED with a resolution of 1920x1200 pixels and a self-calibration mechanism. However, the emergency declared due to COVID-19 has resulted in a temporary relaxation of regulations pertaining domestic reporting, and currently user discretion is recom- mended when using domestic PC and monitors for home reporting. In short, the IT infrastructure needed for remote diagnosis is not unduly demanding and can reason- ably be met even by domestic users, which makes home reporting pos- sible – particularly interesting in terms of social distancing rules due to the Covid-19 pandemic.
1 8 D I G I TA L PAT H O LO G Y D I G I TA L PAT H O LO G Y A more integrative approach The door to simple, cheap, reliable bio-stratification Bringing molecular and digital pathology closer together through a more integrative approach can lead to clear advantages for diagnostic and research workflows, Mark Nicholls reports During the recent Digital Pathology and AI Congress (London) and in his keynote presentation ‘Molecular and digital pathology - the value of an integrative approach’, Professor Viktor Koelzer explored the ben- efits and paid particular attention to colorectal cancer (CRC) during the event. ‘It’s an exciting time in pathology as we better connect tissue morphology and molecular changes using digital pathology and artificial intelligence,’ he told del- egates. Koelzer, who is Attending Pathologist and Assistant Professor at the Institute of Pathology and Molecular Pathology at University of Zurich and University Hospital Zurich, explored recent paradigm changes in clinical diagnostics and research workflows with the poten- tial of predicting molecular features from image data. ‘Information from surgical pathology feeds into molec- ular testing, but we rarely make the loop back. Today we are starting to close this gap,’ said Koelzer. Looking at tumour annotation for molecular analysis, he said chal- lenging areas include the limited reproducibility of visual pathology review, inconsistency with bioin- formatic prediction of tumour cell content using sequencing data and Image-based consensus molecular subtype classification (imCMS) and morphological interpretation with tissue level features the resulting limited correlation of standard pathology assessment with DNA and RNA yield from clinical samples. As the ability to detect somatic variants in cancer samples drives personalised therapy, better tissue classification strategies could help to improve clinical diagnostic workflows. ‘An area of development is tis- sue segmentation by supervised machine learning for the estimation of tumour cell percentage by digital pathology,’ he said. This approach allows correlation between different levels of information and provides accurate area information for each tissue component on a given histol- ogy slide. Excellent reproducibility ‘It allows us to look at the cell- level composition of histology slides at great detail and with excellent reproducibility,” he added, “we can thereby gain additional information from pathology review in an auto- mated fashion that would otherwise be very laborious to obtain.’ Indeed, initial data showed that tissue composition analysis with DNN (deep neural networks) allows analytical robustness, automatisa- tion and standardisation and pro- vides high reproducibility at single cell resolution. DNA-based tumour purity esti- mates are more accurate than vis- ual view or deconvolution from genome-wide omic platforms which, he said, tend to under- as well as over-estimate tumour purity respec- tively. Therefore, digital pathology review using DNN could be used to inform downstream molecular anal- yses better and investigate tissue- based metrics as potential biomark- ers in clinical trials. CRC has significant potential and is a current area of focus for his research team at USZ in collabora- tion with Professor Jens Rittscher and Professor Tim Maughan at the University of Oxford. As part of the CRUK and MRC Infrared spectroscopy as a diagnostic tool New techniques of infrared-based technology are showing strong potential for cost-effective tissue analysis, Mark Nicholls reports. Peter Gardner, Professor of Analytical and Biomedical Spectroscopy at the University of Manchester, outlined how hyperspectral imaging coupled with sophisticated computer algo- rithms can identify and grade can- cerous tissue, as well as offer an indication of prognosis. The technique, Gardner said, speaking at the 6th Digital Pathology Peter Gardner is Professor of Analytical and Biomedical Spectroscopy and a fel- low of the Royal Society of Chemistry at the University of Manchester. He heads a successful biomedical spectroscopy group that focuses on the development of vibrational spectroscopy methods for use in pathology and has demonstrated the utility of the technique for both prostate and breast cancer samples. and AI Congress in London last December, lends itself to automation and would be particularly useful to screen large numbers of biopsy samples for common cancers, such as prostate cancer. Posing the question ‘Infrared spectral pathology – an academ- ic exercise or a new diagnostic tool?’, he explained that infrared micro-spectroscopy uses an array detector with the image of the sample focused onto an array of MCT (Mercury Cadmium Telluride) detectors, so that spectra from each point on the sample can be obtained simultaneously. ‘All tissue contains molecules that vibrate, particularly if you shine infrared light through them,’ explained Gardner. The infrared light is absorbed and if we measure this, we obtain an absorption spec- trum. Because we have thousands of pixels in our image, we have thousands of spectra and this makes up our data.’ Reducing error rates Focusing on prostate cancer, the team liaised with pathologists over the technique with feedback sug- gesting that pre-screening with infrared micro-spectroscopy would help focus on the most important cases and that automated pre or post screening of biopsy samples could reduce error rates. However, Gardner stressed, ‘If looking at tissue with infrared spec- troscopy, we cannot pin down indi- vidual proteins – this is not mass spectrometry – but we can get a spectroscopic fingerprint that might be indicative of something in the tissue. because the wavelength of light is longer than visible light, but the research team believe this is still enough to obtain key spectroscopic information. With no need for stains or dyes, he said, grading for cancer can be shown as well as prognostic infor- mation. ‘For a two-band criterion looking at stages T1 and T2 against T3 and T4, we can obtain sensitivi- ‘The question is, is the fingerprint different enough to say something about that tissue? We can get spec- tral evidence of that tissue and the image has evidence of the peaks in that tissue – we can see the protein peak, for example.’ The professor acknowledged that spatial resolution is an issue – the best is about five microns – simply ties and specificities of 91% and 93% respectively,’ he added. He also outlined how spectral information reveals primary tumour behaviour and whether it is invad- ing surrounding tissue. Infrared identification of the tissue pathol- ogy highlighted the epithelium, smooth muscle, lymphocytes, blood, extracellular matrix, concretion and fibrous stroma. With 2.5 million spectra processed and classified in less than sixty sec- onds with no staining needed, or de-waxing of the sample, a draw- back is the requirement for infrared transparent substrates for pristine results. Despite this, the research team has shown that reasonable results and diagnostic information could be obtained using standard 1mm glass slides just from the region of spectrum using epithelial pix- els. Furthermore, the researchers showed that ‘reasonably good’ clas- sifications of stroma and epithelium could be obtained directly from heavily H&E stained tissue. Gardner – who believes the tech- EUROPEAN HOSPITAL Vol 29 Issue 2/20 Ki67, ER, PR, CD3 Imaging•Fully automatic•For WSI or microscope camera•LIMS IntegratedDigital Pathology Solutionswww.vmscope.de
D I G I TA L PAT H O LO G Y D I G I TA L PAT H O LO G Y 1 9 e approach funded Stratification in Colorectal Cancer or S:CORT consortium (www.scort.org.uk), they have pre- viously developed a cheaper, fast- er method of cancer classification using artificial intelligence to ana- lyse high-resolution images of his- tological slides. This allows the sub- classification of colorectal tumours into one of four distinct consensus molecular subtypes (CMS) and gives an indication of optimal treatment strategies. As histological grading is a poor predictor of disease progression, and CMS cannot be distinguished without gene expression profiling, a clinical need results for better prog- nostic/predictive indicators for the disease. ‘Clinical stratification using molecular data requires sequenc- ing of tissue samples, which is costly and requires the availability of the relevant infrastructure and bioinformatics resource,’ he added, explaining that image analysis can be a cost-effective solution to inter- rogate morphological features as a surrogate for genetic/molecular information. Biological understanding of CRC ‘We show that image-based CMS (imCMS) of CRC can assess clinical impact, produce a molecular pro- file and phenotype information for molecular subtypes of CRC. Using this information could improve our Viktor Koelzer is Assistant Professor at the Institute of Pathology and Molecular Pathology at University Hospital Zurich and Honorary Senior Clinical Researcher at the University of Oxford. He is passion- ate about technology in application to daily diagnostic practice and research, in particular improving patient care through the implementation of high-quality, sci- ence-driven computational image analy- sis approaches with a focus on gastroin- testinal disease and tumour immunology. biological understanding of CRC potentially leading to better clinical stratification and treatment deci- sions, such as performing a surgical resection or giving adjuvant chemo- therapy. In conclusion Professor Koelzer said that Computational models can predict transcriptional subtype of CRC from standard histology sec- tions. ‘imCMS makes sequencing information interpretable through association of morphology, molecu- lar features and outcome data and classifies samples previously unclas- sifiable by RNA expression profil- ing.’ It also gives a novel insight into tumour heterogeneity, is highly prognostic; and classifies endoscop- ic biopsies and resection specimens of CRC enabling patient stratifi- cation in diverse clinical settings. Koelzer sees a promising outlook with a better integrative approach for molecular and digital pathology: ‘Molecular classifiers can be recog- nised and called from H&E images, opening the door to simple, cheap and reliable biological stratification within routine workflows and exist- ing retrospective cohorts.’ ‘We need to put our heads together and exchange ideas’ Digitising pathology – one step further specific For more development has significantly research than 30 years, Barco invested in and to improving workflow and clinical outcomes for healthcare profession- als. Barco researchers work closely with clinicians to obtain a deep understanding of the clinical chal- lenges and workflow realities so that they can incorporate this knowledge while developing innovative ideas for tomorrow’s healthcare products. Toward this goal, Barco has devel- oped display systems and technolo- gies designed to empower clinicians to work more efficiently and diag- nose more accurately to meet the demand of a growing workload in an era of unprecedented healthcare service delivery. Digital pathology is sweeping the globe, adding the convenience of bright displays, sophisticated soft- ware, and digital archives to the mature histopathology process. Ultimate slide-to-eye confidence Digital images are stable over time and can be quickly transported over computer networks to bring the best people and the best images together to improve patient care. Countries vary in their uptake of this new technology, and in the United States of America, the FDA has cleared digital products only for a select subset of IHC applications. Cédric Marchessoux, research engineer at Barco, explains: ‘A lot of challenges need to be addressed before digital pathology can hit the market. First of all, the images are huge, requiring very high resolution imaging devices. Moreover, analys- ing pathology images is a complex practice and exchanging samples or slides between labs is difficult, which prevents effective collabora- tion. That’s why we need to put our heads together and exchange ideas so we can take the digitisation of pathology one step further.’ What people love about Barco pathology displays: Fast viewing, panning and zoom- ing in on digital slides with the powerful Barco display control- lers Intervention-free colour calibra- tion and record-keeping with Medical QAWeb See more details on your slides with a variety of large, bright Barco display models Designed for medical use: clean- able and compliant with inter- national medical safety and emis- sion standards (CE, UL, etc.). www.barco.com False colour image of the classified prostate tissue cores based on their infrared spectra: Red Orange = cancer associated stroma, Green Purple = normal epithelium, = normal stroma. = malignant epithelium, nology is almost ready for clinical translation – concluded: ‘Infrared spectral pathology can be used to analyse tissue and provide diagnos- tically useful information. ‘A preliminary study shows H&E gives enough information to provide initial screening and extremes of staining make no significant differ- ence, though the type of glass does, although that can be standardised, Gardner added.’ www.healthcare-in-europe.com Visible outcomes We help medical professionals enable better health outcomes and work more eﬃ ciently in an increasingly complex healthcare enterprise.
2 0 D I G I TA L PAT H O LO G Y COVID-19 Fast detection of virus antibodies Researchers at Hokkaido University have succeeded in detecting anti-avian influenza virus antibody in blood serum within 20 minutes, using a portable analyser they have developed to conduct rapid on-site bio tests. The microfluidic device to which ~20 µL of samples containing 2 µL of serum will be applied IntelliSite More productive. Insightful decisions. Be more productive with solutions that help you to work smarter. Digital and computational pathology can streamline your workﬂ ow and add intelligence for insightful decision-making. Full digital case sign-out is possible with the Philips IntelliSite Pathology Solution today. Visit our website to learn how Philips supports the transformational change of digital pathology to empower your decision making and precision diagnostics. : B s r o t a u t c A d n a s r o s n e S , . l a t e . K a m a y i h s i N : e c r u o S 0 2 0 2 , 1 2 l i r p A . l a c i m e h C If a suitable reagent is developed, a new portable analyser could be used to detect antibodies against SARS- CoV-2, the causative virus of COVID- 19. Avian influenza is a poultry disease caused by influenza A virus infection. Rapid initial response for a suspected infection and continu- ous surveillance are essential to mitigate the damage from highly pathogenic, transmittable pathogens such as avian influenza viruses. The group, including Keine Nishiyama, a PhD student at Hokkaido University’s Graduate School of Chemical Science and Engineering, and Professor Manabu Tokeshi of the university’s Faculty of Engineering, conducted this study to develop a new method and analyser capable of rapid, facile and selec- tive detection of antibodies. The method is based on conventional fluorescence polarization immuno- assay (FPIA) but applies a different measurement mechanism to make the analyser much smaller and port- able. The analyaer weighs only 5.5 kilograms. Simultaneous examination of multiple samples The combined use of liquid crystal molecules, an image sensor and the microfluidic device makes it possible to simultaneously examine multiple samples and reduces the volume of each sample required. Liquid crystal molecules are capable of controlling the polarisation direc- tion of fluorescent light, while the microfluidic device has a number of microchannels as a measurement vessel. The group also developed a reagent to detect anti-H5 avian influenza virus antibody, a fluores- cein-labelled protein that binds only with the antibody. The reagent was made by reproducing hemaggluti- nin (HA) protein fragments, which are expressed on the surface of H5 avian influenza virus, through gene recombination and by labelling fluo- rescent molecules to the fragments. To make the measurement, serum collected from birds was mixed with the reagent and left for 15 min- utes. The mixture was injected into the microfluidic device and meas- ured with the portable fluorescence polarisation analyser. Molecular movements of the reagent bound with the antibody will be smaller in the liquid, producing a different degree of polarisation from the rea- gent not bound with the antibody. The system can detect anti-H5 avian influenza virus antibody with only two microlitres of serum sample and within 20 minutes. ‘Our analyser could be used to conduct other bio tests,’ Tokeshi said, ‘if suitable rea- gents are developed.’ EUROPEAN HOSPITAL Vol 29 Issue 2/20