Heart Failure (HF) is defined by the heart's reduced ability to pump blood due to a drop in cellular contractility, enlarged anatomy and increased coronary micro-vascular resistance. This loss of pump function accounts for a significant increase in both mortality and morbidity in western society. With the U.K.'s elderly population expanding, HF is rapidly becoming an epidemic. There is currently a 1 in 5 life-time risk of HF and costs associated with acute and long term hospital treatments are accelerating. The significance of the disease has motivated the application of state of the art clinical imaging techniques to aid diagnosis and clinical planning. Measurements of cardiac wall motion, chamber flow patterns and coronary perfusion currently provide high resolution data sets for characterising HF patients. However, the clinical practice of using population-based metrics derived from separate image sets often indicates contradictory treatments plans due to inter-individual variability in pathophysiology. Thus, despite imaging advances, determining optimal treatment strategies for HF patients remains problematic. To exploit the full value of imaging technologies, and the combined information content they produce, requires the ability to integrate multiple types of functional data into a consistent framework. This in turn will support a paradigm shift away from predefined clinical indices determining treatment options and a move towards true personalisation of care based on an individual's physiology.An exciting and highly promising strategy for underpinning this shift is the assimilation of multiple image sets into personalised and biophysically consistent mathematical models. The development of such models provides the ability to capture the multi-factorial cause and effect relationships which link the underlying pathophysiological mechanisms. Furthermore, using a biophysical basis presents unique opportunities to assist with treatment decisions through the derivation of quantities that cannot be imaged but are likely to play a key mechanistic role in HF e.g. tissue stress and pump efficiency.In parallel with imaging advances the approach is also underpinned by the ongoing development of complementary technologies, including improved numerical methods and increased performance per unit cost of computing. This computational progress has accelerated the addition of multi-physics functionality to a range of organ models which have recently been organized into international initiatives such as the IUPS sponsored Physiome and VPH projects. Within these programmes the heart is arguably the most advanced current exemplar of an integrated organ model. As such it represents a promising first candidate with which to focus on an important human disease.My goal during this fellowship will be to focus on personalising and applying these models in clinical and industrial settings for treating HF patients. Model simulations will be focused on quantifying diagnosis, aiding patient selection and guiding interventional planning for specific treatments carried out by leading clinicians based in the cardio-vascular imaging group at Kings College London (KCL). In addition to this direct clinical application of the model, the research will also be focused on the tuning of Left Ventricular Assist Devices (LVADs) which are often connected to the heart in HF to reduce mechanical load by pumping blood from the left ventricle directly into the aorta. Through these applications my aim is to both improve our understanding of this significant cardiovascular disease and demonstrate the potential of biophysical models for improving human healthcare.

Heart Failure (HF) is defined by the heart's reduced ability to pump blood due to a drop in cellular contractility, enlarged anatomy and increased coronary micro-vascular resistance. This loss of pump function accounts for a significant increase in both mortality and morbidity in western society. With the U.K.'s elderly population expanding, HF is rapidly becoming an epidemic. There is currently a 1 in 5 life-time risk of HF and costs associated with acute and long term hospital treatments are accelerating. The significance of the disease has motivated the application of state of the art clinical imaging techniques to aid diagnosis and clinical planning. Measurements of cardiac wall motion, chamber flow patterns and coronary perfusion currently provide high resolution data sets for characterising HF patients. However, the clinical practice of using population-based metrics derived from separate image sets often indicates contradictory treatments plans due to inter-individual variability in pathophysiology. Thus, despite imaging advances, determining optimal treatment strategies for HF patients remains problematic. To exploit the full value of imaging technologies, and the combined information content they produce, requires the ability to integrate multiple types of functional data into a consistent framework. This in turn will support a paradigm shift away from predefined clinical indices determining treatment options and a move towards true personalisation of care based on an individual's physiology.An exciting and highly promising strategy for underpinning this shift is the assimilation of multiple image sets into personalised and biophysically consistent mathematical models. The development of such models provides the ability to capture the multi-factorial cause and effect relationships which link the underlying pathophysiological mechanisms. Furthermore, using a biophysical basis presents unique opportunities to assist with treatment decisions through the derivation of quantities that cannot be imaged but are likely to play a key mechanistic role in HF e.g. tissue stress and pump efficiency.In parallel with imaging advances the approach is also underpinned by the ongoing development of complementary technologies, including improved numerical methods and increased performance per unit cost of computing. This computational progress has accelerated the addition of multi-physics functionality to a range of organ models which have recently been organized into international initiatives such as the IUPS sponsored Physiome and VPH projects. Within these programmes the heart is arguably the most advanced current exemplar of an integrated organ model. As such it represents a promising first candidate with which to focus on an important human disease.My goal during this fellowship will be to focus on personalising and applying these models in clinical and industrial settings for treating HF patients. Model simulations will be focused on quantifying diagnosis, aiding patient selection and guiding interventional planning for specific treatments carried out by leading clinicians based in the cardio-vascular imaging group at Kings College London (KCL). In addition to this direct clinical application of the model, the research will also be focused on the tuning of Left Ventricular Assist Devices (LVADs) which are often connected to the heart in HF to reduce mechanical load by pumping blood from the left ventricle directly into the aorta. Through these applications my aim is to both improve our understanding of this significant cardiovascular disease and demonstrate the potential of biophysical models for improving human healthcare.

This programme aims to change the way medical imaging is currently used in applications where quantitative assessment of disease progression or guidance of treatment is required. Imaging technology traditionally sees the reconstructed image as the end goal, but in reality it is a stepping stone to evaluate some aspect of the state of the patient, which we term the target, e.g. the presence, location, extent and characteristics of a particular disease, function of the heart, response to treatment etc. The image is merely an intermediate visualization, for subsequent interpretation and processing either by the human expert or computer based analysis. Our objectives are to extract information which can be used to inform diagnosis and guide therapy directly from the measurements of the imaging device. We propose a new paradigm whereby the extraction of clinically-relevant information drives the entire imaging process. All medical imaging devices measure some physical attribute of the patient's body, such as the X-ray attenuation in CT, changes acoustic impedance in ultrasound, or the mobility of protons in MRI. These physical attributes may be modulated by changes in structure or metabolic function. Medical images from devices such as MR and CT scanners often take 10s of seconds to many minutes to acquire. The unborn child, the very young, the very old or very ill cannot stay still for this time and methods of addressing motion are inefficient and cannot be applied to all types of imaging. Usually triggering and gating strategies are applied, which result in a low acquisition efficiency (since most of the data is rejected) and often fail due to irregular motion. As a result the images are corrupted by significant motion artifact or blurring.Accurate computational modeling of physiology and pathological processes at different spatial scales has shown how careful measurements from imaging devices might allow the clinician or the medical scientist to infer what is happening in health, in specific diseases and during therapy. Unfortunately, making these accurate measurements is very difficult due to the movement artifacts described above. Imaging systems can provide the therapist, interventionist or surgeon with a 3D navigational map showing where therapy should be delivered and measuring how effective it is. Unfortunately image guided interventions in the moving and deforming tissues of the chest and abdomen is very difficult as the images are often corrupted by motion and as the procedure progresses the images generally diverge from the local anatomy that the interventionist or surgeon is treating.Our programme brings together three different groups of people: computer scientists who construct computer models of anatomy, physiology, pharmacological processes and the dynamics of tissue motion; imaging scientists who develop new ways to reconstruct images of the human body; and clinicians working to provide better treatment for their patients. With these three groups working together we will devise new ways to correct for motion artifact, to produce images of optimal quality that are related directly to clinically relevant measures of tissue composition, microscopic structure and metabolism. We will apply these methods to improve understanding of disease progression; guide therapies and assess response to treatment in cancer arising in the lung and liver; to ischaemic heart disease; to the clinical management of the foetus while still in the womb; and to caring for premature babies and young children.

Magnetic induction tomography (MIT) is a technique for imaging the electrical conductivity in a cross-section of an object. MIT applies a magnetic field from a current-carrying coil to induce eddy currents in the object which are then sensed by an array of other coils. From these signals, an image of conductivity is reconstructed. This proposal brings together two of the world's leading groups in MIT, from Manchester and South Wales, with a programme designed to address the fundamental theoretical and practical problems of making MIT operate reliably with low-conductivity materials (< 10 S/m). The success of this research could produce a major step forward in the application of MIT, with new opportunities in imaging biological tissues and industrial processes. Three specific application areas will be researched: one biomedical, for imaging acute cerebral stroke, one in glass production, for monitoring process parameters to ensure product quality, and one in the oil industry for imaging the process water in an oil/gas pipeline.

Magnetic induction tomography (MIT) is a technique for imaging the electrical conductivity in a cross-section of an object. MIT applies a magnetic field from a current-carrying coil to induce eddy currents in the object which are then sensed by an array of other coils. From these signals, an image of conductivity is reconstructed. This proposal brings together two of the world's leading groups in MIT, from Manchester and South Wales, with a programme designed to address the fundamental theoretical and practical problems of making MIT operate reliably with low-conductivity materials (< 10 S/m). The success of this research could produce a major step forward in the application of MIT, with new opportunities in imaging biological tissues and industrial processes. Three specific application areas will be researched: one biomedical, for imaging acute cerebral stroke, one in glass production, for monitoring process parameters to ensure product quality, and one in the oil industry for imaging the process water in an oil/gas pipeline.