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The FLAIR (Fluid Attenuated Inversion Recovery) MRI sequence developed at Imperial College has transformed the sensitivity of clinical neuroimaging for white matter brain lesions. FLAIR has had significant commercial impact with incorporation as a standard imaging sequence offered by all manufacturers on their MRI scanners. The inclusion of FLAIR in routine diagnostic MRI protocols in radiology centres worldwide provides evidence of the continued extensive reach of impact for better healthcare outcomes through improved diagnosis and management. The use of FLAIR has led to more powerful Phase II trial designs for development of medicine for stroke, neuroinflammatory disorders, epilepsy and neuro-oncology based on imaging outcomes.
Questions about the benign or malignant nature of liver tumours are common and pressing since they determine how the patient is managed. Benign masses are frequently encountered; they usually do not require intervention but are easily mistaken for malignancies with conventional imaging methods. Work at Imperial College demonstrated that microbubble contrast agents have the special property of lingering in both normal liver tissue and in benign solid masses, whereas malignancies do not retain microbubble. The discovery of this property at Imperial has led to their use worldwide as a diagnostic tool. In 2012 NICE recommended their use as being cost-effective for this use.
Temozolomide is a major UK anti-cancer drug development success story. Following chemical synthesis at Aston University, early clinical evaluation of temozolomide carried out at Imperial College optimised how temozolomide was scheduled and delivered to patients to ensure maximum efficacy balanced acceptable side effects. Imperial's early trials demonstrated how the drug could be used effectively to treat patients with a type of brain cancer, glioma, and was pivotal to its subsequent market licensing. ESMO and NICE guidelines recommend temozolomide for use in patients with recurrent glioma and for patients with newly diagnosed Grade IV glioma. Glioma is a relatively rare cancer yet annual sales of temozolomide have been in excess of £900 million per year since 2009. Temozolomide given during and following radiotherapy is now standard of care for glioma and has improved survival compared to previous treatments or radiotherapy alone.
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.
The UCL Centre for Amyloidosis and Acute Phase Proteins has designed and developed new chemical entities targeting serum amyloid P component (SAP), C-reactive protein (CRP) and transthyretin, for novel therapeutic approaches to amyloidosis, Alzheimer's disease, cardiovascular and inflammatory diseases. The UCL spin out company, Pentraxin Therapeutics Ltd, founded by Sir Mark Pepys to hold his intellectual property (IP), has licensed two programmes to GlaxoSmithKline (GSK). These highly synergistic, collaborative multi-million pound developments, strikingly exemplify new working relationships between academia and the pharmaceutical industry.
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.
Imperial researchers in Prof Paul French's photonics group demonstrated one of the first practical FLIM instruments in 1997 using a prototype gated optical intensifier (GOI) developed by Kentech Instruments Ltd and a home-built solid-state ultrafast laser. They subsequently pioneered the use of ultrafast supercontinuum sources (USS) for FLIM. Today wide-field time-gated FLIM is a commercial success and is being widely applied for biomedicine, including for imaging of diseased tissue [e.g. 5] and for FRET (Fluorescence resonance energy transfer) microscopy to assay protein interactions [e.g. 3, 4]. This research thus helped translate FLIM to a wider community, highlighting the potential for tissue imaging, cell biology and drug discovery. It stimulated about £5M of GOI sales for Kentech [section 5, source A], with whom they developed time-gated FLIM technology and applications, and millions of pounds worth of sales of supercontinuum sources for Fianium Ltd [B].
Our research has had a major impact on the way pharmaceutical trials in Alzheimer's disease are conducted. The Boundary Shift Integral technique, which we developed and validated, has changed commercial practice and has become the industry standard for measuring atrophy progression. Our methods have largely replaced previous manual measures and in 2008-13 were used in over 20 large international trials. This had significant economic benefits for several companies providing image analysis services. For UCL alone they generated over £5m of industrial contracts. Additionally, through licensing and collaboration, UCL's research contributed to IXICO establishing a significant market share in this important commercial area.
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 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.