Coordination of an EU Framework VII Large Scale Integrating Project (IP) for Integrative Brain Imaging-Modelling: Request for a Travel Grant

It is becoming apparent to medical experts and healthcare policy makers alike that effectiveness and economy in treatment and prevention are strongly connected with personalisation of service. This trend is underpinned by the ever-increasing demand for better long-term results, but also from the fact that the population (especially in the Western world) is aging and that the medical conditions that are of dominant concern are exactly those that can benefit the most from approaches that are tuned to address the individual's specific profile.At the same time, a second realisation has occurred, one that is connected to the vast rewards that quick and targeted translation of techniques, tools and results from the natural sciences to clinical medicine promises to deliver. Nowadays, engineering and computing principles and techniques are used from the earliest stage to invent, design and manufacture novel devices and protocols of substantial clinical value. The programme that we envisage launching builds on these principles, as they are applied to the human brain. We focus on a particularly inclusive and challenging concept that dominates the operation and regulation of the cerebral environment, i.e. the way fluids (water, in the form of cerebrospinal fluid, and blood) permeate the cerebral tissue and how their flow and transport is regulated. The brain is in constant need of supplies, mainly oxygen and glucose, to function. It has developed a remarkable capability to ensure that these supplies reach all parts of the parenchyma by very sophisticated transport regulation mechanisms; the brain remains stable by being variable . Rather than attempting to maintain invariance, the brain modifies its state to meet external demands. This capability allows it to respond (often in a rapid fashion) to changes in its environment that may be gradual or abrupt. The programme of research aims to bring our understanding of these processes (that is currently incomplete, at best) to a new level. By combining computer modelling, imaging, experiments and clinical observations, we shall:-improve patient safety by optimising and rationalising diagnosis and interventions-move substantially towards patient-specific healthcare provision-enhance our understanding of the aetiology and treatment alternatives of neurological diseaseThe level of expertise necessary to achieve these goals necessitates the formation of a wide international consortium of experts from academia, industry and medicine. The present bid requests resources to facilitate this consortium-building exercise, by enabling the PI to travel to select sites and negotiate effectively the integration of such expert partners in this consortium.

We seek resources to support the formation of an EU Integrating Project; within this framework, a wholly new, potentially revolutionary, knowledge-base and modelling range for the behaviour of the cerebral environment and for brain transport regulation will be developed. The major short term impact of the core analytical and computational development will be on the scientific and clinical community. Exploitation in terms of clinical and industrial outcome during the lifetime of the project focuses to the spin-offs from the core technology. In the longer term, only a proven, integrated model of the type that is proposed here can deliver the promise of improved treatment of the target disease processes based on an integrative understanding of the interaction of brain & water transport physics, biology and physiology. In effect, this programme does not represent an incremental development, but rather a radical review of brain regulation processes, underpinned by the best imaging and modelling tools available at the present time. Regarding scientific impact, this will materialise by: -integrating the modelling into the framework of the wider community, thus encouraging post-project take-up and spin-off into parallel and prospective disease studies. -publishing in high-impact journals, to the immediate and obvious benefit of the groups and individuals concerned. As far as clinical impact is concerned, the major exploitation during the course of the project will be the increased understanding engendered in the participating clinicians and, by dissemination and publication, in other centres. The primary clinical exploitation will follow when the model is validated in clinical trials. The improvement in healthcare practice will be tangible and measurable, we believe, and will be reported as it becomes available. Industrial impact will be realised through relevant partners that will explore the possibility of the establishment of a spin-out company to exploit project-related developments, as described in the Project Consortium Agreement (an obligatory document for Framework VII Programmes). Impact in this aspect will take the form of tools & computational-imaging techniques and devices (implants and monitoring equipment). For the former, we envisage that the models and imaging protocols devised (separately and as a suite) will have substantial value and significant uptake by clinical experts (first within the consortium and then beyond) will take place. These tools and knowledge will, at the same time, be used for better and improved design of medical devices, that have substantial commercial value as sophisticated equipment. In summary, the impact of this project lies on the fact that the new knowledge and modelling-imaging tools we shall be generating have the potential to change drastically the way we understand cerebral processes. This new level of knowledge translates directly to patient healthcare, clinical practice and scientific innovation.