Projects
These highlighted projects use our imaging facilities and focus on our main research themes.
Multi-modality Translational Imaging
We are the coordinator for the BIOIMAGE-NMD project, which is an FP7 funded translational research programme.
The aims of the project are to develop and evaluate imaging biomarkers for basic in vivo research and clinical trials in the neuromuscular disease, Duchenne muscular dystrophy (DMD).
Imaging has an essential and central role in the evaluation of patients with rare diseases. Non-invasive outcome measures that demonstrate early response to novel therapies are urgently required. They are of particular importance in rare diseases where large scale conventional clinical trials are unfeasible.
BIOIMAGE-NMD programme
The BIOIMAGE-NMD programme combines expertise across our imaging portfolio to address this important problem.
Within our radiotracer production facilities we are developing 18F tagging of antisense oligoneucleotide (AON) therapeutic agents created by our research partner, Prosensa Therapeutics.
We are developing new diffusion MRI imaging techniques to non-invasively image muscle fibre damage. These are first evaluated in transgenic muscular dystrophy models using our preclinical MRI scanner.
We are translating the new techniques into tools for clinical imaging to underpin the clinical trials in patients already underway using our 3T scanners.
The programme has nine academic and SME partners across Europe.
Methodologies
Highly accelerated quantitative imaging by compressed sensing (IMPRESS) is a Medical Research Council funded project to develop and validate highly accelerated quantitative MRI.
Quantitative imaging by MRI has an established role in clinical research as it is non-invasive and doesn’t use ionising radiation. Examples include skeletal muscle therapy trials in neuromuscular diseases, and trials to determine the effect of diet or exercise interventions on liver and pancreas fat depots in type 2 diabetes.
MRI scans can require patients to lie still for anything up to one hour and often to repeatedly hold their breath. Adding MRI to a clinical trial can also be expensive.
This project develops and validates novel acceleration techniques that will reduce scan times by up to a factor of five. This improves patient comfort and reduces cost.
In particular the IMPRESS project will deliver three accelerated clinical research applications of proven utility. These include:
- skeletal muscle fat fraction assessment of disease progression in muscular dystrophy
- quantification of liver and pancreas fat content in type 2 diabetes
- cardiac function assessment in neuromuscular diseases
Methodological MRI development work is carried out on our clinical and preclinical MRI systems by members of the MR Physics team.
Tracers
We harness the power of IVIS by developing novel bioluminescent tracers to study tissue injury and repair processes in the intact animal.
IVIS spectrum is a 3D optical imaging system that allows non-invasive, real-time longitudinal monitoring of disease progression and therapeutic responses.
Imaging liver fibro genesis
The generation of fluorophores, which facilitate near infrared labelling of proteins, have made possible identification and validation of novel targets with in vivo disease models.
Liver fibrosis, regardless of aetiology follows a common course:
- repeated epithelial cell damage to;
- chronic inflammation to;
- scar cell activation and persistence to;
- fibrosis
A central event in fibrosis progression is the activation of scar forming cells, Hepatic Myofibroblasts (HM).
We have used a fluorescently labelled single chain antibody which recognises HM in conjunction with optical imaging technology. This monitors the process of liver fibrosis in vivo in liver fibrosis models.
Cell tracking
Genetic manipulation of cells lines to express the luciferase reporter gene has allowed researches at Newcastle to use in vivo bioluminescent imaging to monitor physiological processes in real time. This includes:
- cell tracking
- longitudinal tumour cell growth
- disease progression
- assessing the response to therapy
Multimodality in vivo imaging
Every imaging modality has inherent advantages and disadvantages. Optical imaging lacks anatomical localisation. That is why we are developing multimodal methods to image subjects sequentially on different imaging platforms. This allows the maximum amount of information to be obtained to answer a biological question.
Functional abnormalities obtained with in vivo fluorescent imaging (IVIS) can be accurately anatomically localised with Computerised Tomography (CT).
These studies are conducted using our IVIS spectrum system.
Clinical trials
This programme is using Rituximab for the treatment of fatigue in patients with primary biliary cirrhosis (PBC). It is a National Institute for Reproductive Health funded clinical trial under the Efficacy and Mechanism Evaluation programme.
Fatigue is a significant problem for many of our patients. Our pioneering collaboration between the Clinical Hepatology Research and MR Teams at Newcastle has demonstrated that the way the muscle responds to energetic demand is altered in patients with PBC. This is postulated to be associated with the level of an anti-mitochondrial antibody that is characteristically altered in these patients.
This study trials the use of the drug Rituximab in patients with PBC. Rituximab is an existing and effective treatment to reduce the production of antibodies in the body and we believe will therefore reduce the fatigue in our patients.