The use of flexible endoscopes for endoscopic retrograde cholangiopancreatography (ERCP) is increasing as it represents a relatively non-invasive method for the diagnosis and treatment of certain conditions of the biliary and pancreatic ductal systems, such as gallstones, undefined biliary strictures, bile duct injury or leaks, and cancer. The design of duodenoscopes, however, is complex; they have long narrow channels and a recessed elevator at the distal end that enables good use of any accessories. All the external surfaces and internal channels are in contact with body fluids, presenting a risk of contamination and transmission of infection from patient to patient as well as from patient to endoscopy personnel. As these flexible devices are heat labile and not suitable for steam sterilization, careful cleaning (reprocessing) is needed to minimize the risk of contamination.

A recent event on Hygiene Solutions in Endoscopy was held at PENTAX Medical R&D Center (October 2019, Augsburg, Germany) to discuss insights on the need for infection control and how to minimize contamination. The event brought together a number of key opinion leaders in the field of ERCP hygiene (endoscopists, microbiologists and chief nurses) and included Paul Caesar, Hygiene and Infection Prevention expert at the Tjongerschans Hospital (Heerenveen, The Netherlands), Dr Hudson Garrett Jr., Global Chief Clinical Officer at PENTAX Medical and Assistant Professor of Medicine (Division of Infectious Diseases) at the University of Louisville School of Medicine, Kentucky, USA, as well as Wolfgang Mayer, Managing Director of Digital Endoscopy at PENTAX Medical.

Endoscopy-associated infection
The healthcare community is increasingly aware of the risk of hospital-acquired infection associated with endoscopy following documentation of several outbreaks of patient infections linked to duodenoscopes in the USA and around the world in the last decade as well as regulatory recalls. However, Paul Caesar made the point that in reality there is very little data regarding infection rates. One of the issues is that patients are discharged from hospital more and more quickly following procedures. Then, if any infection subsequently develops, the patient usually attends their local general practitioner and the link to the endoscopy is not made. The point was made that currently no surveillance is done for post-endoscopy infection and this should be put into place to generate reliable data on infection rates.

Endoscope reprocessing
The role of endoscope reprocessing is crucial for mitigating the risk of infection and is achieved by mechanical cleaning detergent cleaning, high level disinfection, and rinsing and drying (Figs 1–3). However, research shows that in 45% of cases key reprocessing steps are skipped. Additionally, 75% of the reprocessing staff reported time pressures and non-compliance with guidelines related to reprocessing as a result. Paul Caesar emphasized this point saying, “Manual cleaning is still the most important step in reprocessing. However, in daily practice this stage is often downgraded to just a simple flush and brush. I call upon the field, to shift from reprocessing quantity to quality”. Another crucial step is to ensure that the device is thoroughly dried before storage. This reduces the risk of biofilm formation and bacterial growth. However, there are currently no official guidelines for the optimum drying time; even within Europe alone different countries use different drying times.

Suggestions for the improvement of reprocessing included:
1. proper explanation to and understanding by staff of the importance of the reprocessing stages to gain their commitment to following the procedure fully;
2. use of shorter visual pictogram explanations of the reprocessing stages rather than manuals that are approximately 150 pages long and are too complicated to thoroughly read and understand; and
3. traceability and tagging of the people performing the various tasks so that all the steps can be scanned and shown to be done in an optimal fashion.

Improving duodenoscope design
According to Calderwood et al., patient-to-patient transmission of infection has been linked to the elevator channel endoscopes (such as duodenoscopes) and attributed to persistent contamination of the elevator mechanism, the elevator cable and the cable channel. One solution to infection control is to use disposable duodenoscopes. However, this is not practical for every endoscopy because of the cost and the environmental impact. The one-time use of a disposable device is therefore recommended only for high-risk patients.

Hudson Garrett confirmed the company’s commitment to minimizing infection outbreaks with careful consideration of advice and requirements from the CDC (Centers for Disease Control and Prevention) and FDA (U.S. Food and Drug Administration) in the USA, and “using integrated feedback from all clinical stakeholders, optimizing reprocessing processes, and innovating products to directly tackle patient safety and infection prevention needs”. This has led to the development of a duodenoscope with a disposable distal cap with integrated elevator, hence eliminating the part of the device that is most associated with contamination. Additionally, use of the company’s dedicated dryer helps to ensure the device is fully dry, reducing the risk of microbial growth and subsequent potential contamination that can result from moisture. PENTAX Medical also has a strong commitment to the training of reprocessing staff, which (according to current data) requires a minimum of 8 hours to be done properly.

Hospitals have evolved considerably over the years from the early Greek temples of healing, asclepeia, to the large dark, cramped multiple-patient wards of the early Western hospitals, essentially for those who could not afford private care at home, and the brighter, more open smaller ward or single room hospitals of today. These changes have come about as medicine has advanced, technology has progressed and societal and patient conditions and demands have changed. It is difficult to predict how the hospital of tomorrow will look with any precision, but we can make some fairly accurate suggestions based on current trends and developments.

by Prof Jean-Louis Vincent

One key change is that intensive care unit (ICU) patients will represent an increasingly large proportion of hospital patients in the future. There are several reasons for this. First, improved disease prevention and primary care, shorter post-surgery hospital stays and facilitated home care will mean that patients who are hospitalized will be more seriously ill than at present and more likely to need intensive care. Another reason for the increased need for ICU beds is prolonged life expectancy. Improved healthcare means that the average age of the population is increasing worldwide, and older patients are more likely to have multiple comorbidities and to develop complex acute illness. In one report from the US, the number of hospital beds decreased by 2.2% while ICU beds increased by 17.8% over a 10-year period.

As such, the hospital of the future will be composed of a large number of ICU beds with relatively few hospital beds (other than daycare) for other patients (see figure). The ICU may be a physical unit at a strategic place within the hospital, or it may be a more “virtual” ICU with beds dispersed around the hospital. It is possible that in the future all hospital beds will have the potential to be an ICU bed, limiting the need for patient transfers between wards and reducing the time for key ICU interventions to be put into place when a patient is identified as deteriorating. This could also reduce any problems associated with ICU bed shortages. The potential limitations of such an approach include the need for all nursing staff to be trained in intensive care.

So, assuming that the physical ICU structure remains, at least for the near future, what will it look like? With current patient demands for privacy and problems associated with multiresistant pathogens, the ICU will almost certainly consist of multiple single rooms. These rooms will be large and spacious with easy access to the bed from all sides and room for relatives to visit and stay and for the patient to mobilize when possible. The rooms will have large interactive screens with access to patient results and monitored parameters, the ability to call and speak to healthcare staff via telemedicine, and of course standard entertainment channels. Because almost all monitoring, of hemodynamic parameters as well as laboratory values, will be non-invasive and results transmitted to the doctor’s smartphone and to central remote monitoring hubs by wireless technology, there will be much less visible equipment, cables and tubes. What equipment is still necessary will be much smaller, less cumbersome and more user-friendly than at present. Continuous monitoring, multiple feedback systems and computerized interrogation across multiple systems and disciplines will make ICUs much safer with fewer iatrogenic errors.

Visiting hours will be unrestricted throughout the hospital, including in the ICU, and family members, including children, will be welcome. This open access and greater involvement will impact positively on patients and on their families, reducing anxiety and helping to reduce post-ICU stress.

The hospital as a whole will be much more technology oriented than at present and interactive screens will be responsible for much of the routine administration with robots involved in basic services, such as delivery of food and medication, as well as patient mobilization and social stimulation. Care will be more patient-centered and personalized and the flow from home to general ward to ICU will be much more of a continuum. Indeed, some patients may be discharged directly home from the ICU, an option facilitated by continued surveillance using telemedicine. Patients and healthcare staff will have continuous and real-time access to patient medical results and data. Such data will be fed automatically into large international databases to help continuously improve patient management. This process will have become routine and current issues related to data privacy will no longer be a problem.
There will be fewer medical and nursing staff physically present on the wards as telemedicine will be more widely used, enabling remote control of drug infusions and other interventions and e-consultations at the request of the physician or patient. Although healthcare staff may therefore be seen less frequently, they will actually be able to spend more quality time talking to patients and their families.

Technological advances are changing how the world around us operates and the hospital is no exception. Future hospital and ICU design needs to provide flexibility and adaptability to continued technological developments. Healthcare workers and patients will need time to adapt to these changes and to learn how best to use them to improve care and outcomes. We must all be involved in developing the ICU of the future. As Abraham Lincoln said, “The best way to predict the future is to create it”.

Suggested reading:
1. Vincent JL. Critical care–where have we been and where are we going? Crit Care 2013;17 Suppl 1:S2.
2. Halpern NA, Goldman DA, Tan KS et al. Trends in critical care beds and use among population groups and Medicare and Medicaid beneficiaries in the United States: 2000-2010. Crit Care Med 2016;44:1490-1499.
3. Ewbank L, Thompson J, McKenna H: NHS hospital bed numbers: past, present, future. https://www kingsfund org uk/publications/nhs-hospital-bed-numbers#hospital-beds-in-england-and-abroad.
4. Vincent JL, Creteur J. The hospital of tomorrow in 10 points. Crit Care 2017;21:93.
5. Vincent JL, Michard F, Saugel B. Intensive care medicine in 2050: towards critical care without central lines. Intensive Care Med 2018;44:922-924.
6.Denis K, Bidet F, Egault J et al. Utilization of Robo-K for improving walking and balance in patients affected by neurological injuries: A preliminary study. Ann Phys Rehabil Med 2016;59S:e88.
7. Bailly S, Meyfroidt G, Timsit JF. What’s new in ICU in 2050: big data and machine learning. Intensive Care Med 2018; 44:1524-1527.
8.Michard F, Pinsky MR, Vincent JL. Intensive care medicine in 2050: NEWS for hemodynamic monitoring. Intensive Care Med 2017;43:440-442.

The author
Jean-Louis Vincent, MD, PhD
Dept of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium

Functional magnetic resonance imaging (fMRI) is by far the principal method used to investigate the brain’s cortical areas and subcortical structures. fMRI has dramatically transformed perceptions of the human brain, allowing precise delineation of regions associated with a vast range of external stimuli and moods – ranging from depression and anger to laughter and play. 
Researchers are now exploring further expansion in the scope of fMRI. These range from the development of more precise sensors and probes with quicker response times to the use of fMRI in new applications such as artificial intelligence. Some have even sought to extract images seen by viewers directly out of their brains.

From dog language to crocodile music
Some have also sought to see if fMRI can work in other species of living things.
In 2016, scientists in Hungary concluded that dogs can understand the meaning and tone of human speech, and that they process language in the same way humans do. To reach this conclusion, they managed to get 13 pet dogs to lie completely motionless in an fMRI scanner for eight minutes while wearing earphones and a radio-frequency coil on their heads.
Earlier this year, a team at Germany’s Ruhr-University in Bochum went further than canines by using fMRI to study the brain of a Nile crocodile as it heard complex sounds, including classical music by Bach.

The eye sees, the brain predicts vision
Given the increasing number of ultra-high field systems available worldwide, experts expect a dramatic impact on our understanding of the brain due to sustained enhancements in resolution (both spatial and temporal), as well as in sensitivity and specificity.
Early this year, researchers from the University of Glasgow published results of a fMRI-based experiment to confirm the capability of the visual cortex to make predictions about what a viewer would see next. The study sought some answers to a seemingly perplexing question. Human beings move their eyes approximately four times per second, requiring their brains to process new visual data every 250 milliseconds. In spite of such rapid and constant variation in perspective and image, how is it that the world remains stable ?
The functional MRI used by the Glasgow researchers showed that the brain rapidly adjusts its predictions, with the visual cortex feeding back updates to a new predicted coordinate every time the eyes move.

The Glasgow study established the importance of fMRI in new frontiers of neuroscience research. fMRI is now seen as a means to contribute to research into mental illness as well as help the development of artificial intelligence. Indeed, a better understanding of the predictive mechanism in the human brain may directly lead to breakthroughs in brain-inspired artificial intelligence in the future – especially in terms of visual predictive capabilities.

The role of calcium ions in brain activity
Beyond such frontiers, MRI technology is also undergoing other forms of evolution. Some of these, which involve new sensors and pathways to monitor neural activity deep within the brain, are not just path-breaking but also offer the possibility of profound new insights into understanding how human beings think.
One of the most exciting developments in such a context involves the tracking of calcium ions, which are closely correlated to neuronal firing and brain signalling. MRI typically detects changes in blood flow, and its utility derives from the fact that when a region of the brain is in use and neuronal activation ensues, blood flow to that region also increases. However, such a process provides only indirect clues; the signals are difficult to attribute to a specific underlying cause. By contrast, sensing based on calcium ions may allow linkage of neuron activity patterns to specific brain functions, and thereby enable researchers to understand how different parts of the brain intercommunicate during particular tasks.
Indeed, it has been several years since neuroscientists know that calcium ions rush into a cell after a neuron fires an electrical impulse, and have used fluorescent molecules to label calcium and then image it via traditional microscopy. Though the technique has allowed for precisely tracking neuron activity, its practical use has been limited to small regions of the brain.

MIT designs calcium detecting molecular probe
At the Massachusetts Institute of Technology (MIT), researchers have sought a way to image calcium using MRI, in order to allow for the analysis of much larger volumes of brain tissue than was possible by fluorescent labelling. To do this, the MIT researchers designed a new molecular probe whose architecture can detect subtle changes in calcium concentrations outside of cells and respond in a way that can be tracked with MRI. Such a process allows for direct correlation to neural activity deep within the part of the brain known as the striatum.
Tests in rats enabled the MIT researchers to establish that calcium sensors accurately detect changes in neural activity from electrical or chemical stimulation. The levels of extracellular calcium correlate with low neuron activity. In other words, when calcium concentrations drop, neurons in the area are firing electrical impulses.
The goal of the researchers is to greatly enhance precision in mapping neural activity patterns. By measuring activity in different regions of the brain, they hope to find how different types of sensory stimuli are encoded by the spatial pattern of neural activity which is induced.

The MIT probe essentially consists of a sensor made up of two kinds of particles which bind in the presence of calcium. The first is synaptotagmin, a naturally occurring calcium-binding protein, and the other a lipid-coated magnetic iron oxide nanoparticle which binds to synaptotagmin, but does this only if calcium is present. Calcium binding leads to the particles clumping together, and appearing darker in the MRI image.
The researchers are now attempting to increase the speed of response by the sensor, which currently requires a few seconds after the stimulation. A more important goal is to modify the sensor such that it can pass through the blood-brain barrier. This would enable the delivery of the particles without the need to inject them directly in the test site, as is required at present.
Research into new sensors and neurochemical pathways, as being done at MIT, will no doubt open new vistas in fMRI. However, other efforts too are expected to greatly enhance the range and spectrum of its applications.

Powering up fMRI machines
In May 2013, the European Journal of Radiology published results of a study comparing fMRI at 7T compared to 3T in imaging of the amygdala, a ventral brain region of specific importance to psychiatry and psychology. Traditionally, MRI imaging of such areas is prone to signal losses along susceptibility borders – alongside signal fluctuations due to physiological artifacts from respiration and cardiac action. The increase from 3T to 7T showed a significant gain in percental signal change and demonstrated the potential benefits of ultra-high field fMRI in ventral brain areas.

UC Berkeley targets massive resolution boost in fMRI
More recent efforts are also aimed at enhancing resolution. Today’s top-of-the line scanners, incorporating 10T magnets, can typically localize activity within a region comprising 100,000 neurons or more, about the size of a grain of rice. To be able to concentrate more finely, on smaller groups of neurons, requires a bottom-up re-design of almost the entire gamut of scanner components and sub-systems.
The University of California at Berkeley is currently targeting a 20-fold boost in fMRI resolution in order to provide the most detailed images of the brain ever seen. The project is funded by a BRAIN Initiative grant from the National Institutes of Health.

New approach to fMRI design and architecture
The leap in resolution will be directly due to innovations in hardware design, scanner control and image computation. Currently, spatial resolution of fMRI recordings is based on variations in the magnetic field as well as, indirectly, on the size of detector. The latter consist of coils of wire, which are arrayed around the head of a subject and pick up signals. The Berkeley system uses a far larger number of smaller coils than clinical MRIs, which use smaller numbers of large coils. The result is straightforward – a much higher resolution of the brain’s outer surface, which is needed to identify key layers of the cortex.
Reducing dimensions in such ultra-high resolution MRI holds the key to image the brain in functional regions, where neurons are all essentially involved in the same type of processing. The target which researchers hope to reach is in the range of 0.4 millimetres This is because the cerebral cortex, the brain’s outer layer, consists of columns of neurons which correspond to a specific sensory feature (such as the vertical rather than horizontal edge of an object) and such columns are 0.4 millimetres on the side and 2 millimetres long. The Berkeley researchers are reported to be confident of their ability to build machines which can scan down to the 0.4 millimetre target by 2019.

Peering into the brain’s depths
If successful, the new fMRIs would allow researchers to study cortical microcircuits and glimpse the deepest recesses of human brain function so far. The developers of the system are ambitious. They aim to provide “the most advanced view yet of how properties of the mind, such as perception, memory and consciousness, emerge from brain operations.” This will open ways to observe disturbances in brain structures and functions, and it is hoped, radically enhance the diagnosis and understanding of neurological diseases.

Extracting images out of the brain
One of the most far-reaching possibilities of fMRI was recently announced by a team from the Japan’s Kyoto University, who used machine-learning and artificial intelligence to translate brain activity into images in test subjects.
These ranged from pictures being looked at by the subjects, to things they remembered seeing. The images included a lion, a fly, a DVD player, a postbox, alphabets and geometric shapes, and were recreated pixel by pixel, based on a deep neural network (DNN). 
The images were projected on to a screen in an fMRI scanner, with the heads of subjects secured in place via a bar on which they had to bite down. The subjects, who participated in multiple scanning sessions for a period of more than 10 months, stared at each image for several seconds before taking a rest. After this, they had to recall one of the images seen previously and picture it in their mind.
The DNN was then used to decode the signals recorded by the fMRI scanner and produce a computer-generated reconstructed image of what the participants saw.