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The capacity for cognitive function may be missed by clinical examination in severely disabled survivors of acquired brain injuries, resulting in individuals being mislabelled as being in the vegetative state (VS). Work from David Menon and John Pickard has shown that functional brain imaging provides a more consistent and less observer-dependent means of detecting and quantifying such cognitive capacity. As a result of this work, the use of functional imaging has been integrated into clinical protocols as the basis for: identifying patients with such covert cognition; prognosticating on outcome; defining a rational framework for patient selection in clinical trials; and exploring the use of brain-machine interfaces to improve communication with such patients.
CANTAB-Paired Associates Learning (PAL) was developed to detect early memory problems in Alzheimer's disease; and was recently (in 2012) launched by Cambridge Cognition (floated on the London Stock Exchange in April 2013) as a mobile (iPad) application (CANTABmobile™) suitable for use in GP clinics. This and other cognitive tests from the CANTAB battery have also been employed in 77 clinical trials since 2008, involving hundreds of sites world-wide, by most of the major pharmaceutical companies and by biotech, device and nutraceutical companies. CANTABmobile™ currently has 166 licensed user-practitioners including six clinical commissioning groups implementing the national initiative for early diagnosis.
Powell's work focuses on outcomes after traumatic brain injury. In 1995 she established an innovative community-based multidisciplinary neurorehabilitation service — the Outreach Team — and evaluated it via a randomised controlled trial. The positive findings have informed policy and service developments internationally. In parallel, she developed a new outcome instrument [the BICRO] to evaluate psychosocial functioning; this is now used by clinicians in 10+ countries. The BICRO informed the subsequent development and validation of a cross-cultural instrument for assessing quality of life after brain injury [the QOLIBRI]; Powell was a member of the Steering Group which directed the complex international collaborative QOLIBRI project. The QOLIBRI is now available in many languages, and has been fully validated in six. There are 400+ registered users in over 35 countries, more than 200 being clinical service providers; it is a formally recommended tool for public health services in Finland and the US; and it is being used as an outcome measure in numerous treatment evaluations and prospective studies worldwide.
For stroke patients and any patient undergoing surgery the time period from diagnosis to treatment is a major factor in clinical outcomes. Research carried out at the University of Warwick has led to the development of sensors that can be used to measure, in whole unprocessed blood, diagnostically useful analytes that can be used to select the best therapeutic treatments. Point-of- care diagnosis and prompt referral to an appropriate care pathway, facilitated by the use of biosensors, will result in efficiency savings for healthcare professionals and the NHS in the long- term, and will also improve patient outcomes. To commercialize these biosensors, Sarissa Biomedical Ltd was founded in 2002, as a UK-based spinout from the University of Warwick. Sarissa sells, around the world, microelectrode biosensors fabricated by a unique enzyme deposition technology protected by patents filed in 2004 and 2008 by the University of Warwick. The diagnostic sensors are based on technology that incorporates Ruthenium Purple and use a sol-gel coating to entrap enzymes on a microelectrode. Sarissa is pursuing human trials of its biosensors as diagnostic tools in two main areas: stroke, and trauma with associated sepsis.
VisensiaTM is a bedside `early warning' system, deployed in many hospitals in the UK and US, which automatically analyses hospital patients' vital signs, produces simple-to-read scores, and alerts healthcare staff to any deterioration in a patient's condition. It resulted from research in this Department, commercialised by Oxford BioSignals Ltd (£1.5m sales to date, and 137 licences sold since 2010). VisensiaTM reduces the number of patients already in hospital who suffer an unexpected cardiac arrest or need an unplanned transfer to intensive care. The US Food and Drug Administration (FDA) approved the system's use after a 1000-patient clinical trial. There were no unexpected fatal cardiac arrests on the wards where the clinical trial took place in the three years after VisensiaTM. was deployed.
The Boutelle team has developed a biosensor that uses rapid-sampling microdialysis (rsMD) to detect ischaemia (restricted blood supply to tissue) during surgery and intensive care. The rsMD biosensor is implanted into tissue at risk and provides a real-time readout of chemical markers of metabolism. By 2009, technical improvements researched in the Department of Bioengineering had made the system suitable for routine clinical use. The system has reduced morbidity and mortality by alerting the surgical team to otherwise undetected ischaemia. It has been used by an international consortium of clinical centres to help decide treatment in approximately 100 patients with brain injury. More recently it was adopted by a Portsmouth hospital to monitor cancer patients undergoing reconstruction of the face and jaw; the biosensor detected a failure of perfusion in transplanted tissue in two of the first ten patients, prompting the surgical team to remove otherwise undetected blood clots that could have led to death from septicaemia.
Professor Alexander's work on diffusion magnetic resonance imaging (MRI) modelling and processing has had significant and lasting impact on medical practice. In particular, neurosurgical support systems rely on his work to map the major connection pathways in the brain, helping the surgeons avoid damaging them during intervention. Specific examples are in epilepsy, where, since 2010, surgeons perform about one operation per week using these systems, and brain tumour resection, where surgeons in Milan have since early 2013 been using a similar system based on UCL's latest microstructure imaging techniques. The key impact is on patients, whose likelihood of permanent post-operative deficits in, for example, visual, verbal or motor skills, is significantly reduced.
Novel methods of measurement developed by Marek Czosnyka, Peter Hutchinson, David Menon and John Pickard have provided new insights into the pathophysiology of brain injury, led to commercial applications, and influenced patient care in terms of improved outcome for clinical trials. Multimodality brain monitoring of intracranial pressure (ICP), brain oxygen and microdialysis; PET/MRI imaging of critically ill patients; and computerised CSF infusion tests for shunt function in hydrocephalus have each impacted on the clinical practice and the ability to evaluate novel treatments and interventions in brain injury. This work has led directly to the establishment of a National Institute for Health Research (NIHR) Health Technology Cooperative for Brain Injury.
Research by Professor Karl Friston at UCL has led to the development of Statistical Parametric Mapping (SPM), a statistical framework and software package. By providing a way to analyse signals measured from the human brain in MRI scanners, SPM triggered the creation of an entirely new field of imaging neuroscience. Beneficiaries include: commercial manufacturers who provide imaging equipment; healthcare practitioners and patients, where SPM is used to deliver new treatments; pharmaceutical industries using SPM to deliver clinical trials; the IT industry developing new software based on SPM; and entirely new industries such as neuromarketing that could only have been created once SPM had been invented.
The University of Nottingham's Children's Brain Tumour Research Centre developed new NHS evidence-accredited referral guidelines, published in 2008, to reduce diagnostic delays for children with brain tumours. Their messages were disseminated through an awareness campaign, `HeadSmart — Be Brain Tumour Aware', launched in 2011. Three months post-launch, 11% of the UK population (over 14 million people) and 73% of paediatricians were aware of HeadSmart, and diagnostic confidence among paediatricians had risen from 32% to 54%. The time from symptom onset to brain tumour diagnosis reduced from 14.4 weeks in 2006 to 6.9 weeks in 2013. This strategy is a `world first' in paediatric brain tumour, now being emulated internationally.