My research interests are in cardiac and atherosclerosis imaging, using CT, MRI and nuclear methods. After medical training in UK and Australia, my PhD at the University of Cambridge described the first use of FDG PET for atherosclerotic plaque imaging and was funded by a British Heart Foundation Clinical Research Fellowship.
I was awarded a British Heart Foundation International Fellowship to work with Professor Zahi Fayad at Mount Sinai Medical Centre in New York. This allowed me to develop further my interest in atherosclerosis imaging using MRI, CT and targeted contrast agents.
I was a British Atherosclerosis Society Young Investigator in 2003, and the Society of Nuclear Medicine Young Investigator in 2006. Collaborative work between my group and colleagues at Edinburgh University describing vascular NaF PET imaging for predicting heart attack has won the 2011 RSNA Young Investigator Prize and the 2012 Parmley prize from the American College of Cardiology.
I was a member of the Programme Committee of the British Cardiovascular Society from 2010 to 2015. In 2013, I was elected a member of the SHAPE scientific advisory board and the MRC-MHRA PET Imaging Advisory Committee. In 2013, I was appointed to the Editorial Board of Heart and I am responsible for Education in Heart – Imaging. I am also the Digital Media Editor at Heart.
My research is supported by HEFCE, the British Heart Foundation, the EPSRC, the Wellcome Trust, the Evelyn Trust, the Academy of Medical Sciences and the NIHR Cambridge Biomedical Research Centre.
Insights into the pathophysiology and risk of clinical events in vascular disease using imaging
In atherosclerosis, inflammation, neovascularisation, hypoxia and calcification are drivers of plaque destabilisation and clinical events such as myocardial infarction and stroke. Conventional x-ray angiography does not provide information about the extent of these processes in the arterial wall, and as a consequence is a poor predictor of future events.
The aim of our research is to use non-invasive imaging to answer four related questions. Firstly, can we quantify the degree of arterial inflammation? Secondly, can we track the effects of therapy on arterial inflammation? Thirdly, can we use imaging to inform about the biology of arterial disease, and finally, can imaging improve our predictions about the risk of future clinical events?
Using PET/CT imaging, we can measure the glucose analogue fluorodeoxyglucose (FDG) where it accumulates in plaque macrophages. This allows us to identify symptomatic lesions causing TIA and stroke. We have demonstrated that arterial FDG uptake correlates with the number of cardiovascular risk factors and with the presence of inflammatory biomarkers of inflammation such as CRP and MMP9. Arterial FDG measures are also highly reproducible. Recent work has also revealed that inflamed plaques on PET imaging have larger lipid cores on MR and ultrasound imaging (suggesting vulnerability).
To image coronary artery inflammation, there are several hurdles to overcome, including coronary and respiratory motion and the avid accumulation of FDG by myocardial cells (swamping any potential coronary artery FDG uptake). To overcome these challenges, we are testing several novel PET imaging agents in both clinical and pre-clinical models of vascular disease.
As part of the second aim, we have completed several multi-centre clinical trials of novel anti-atherosclerosis agents (with GSK, Roche, Merck and Genentech). In this work, we use FDG PET/CT as a surrogate marker of vascular inflammation. in this way, we can obtain early readouts of drug efficacy with far fewer subjects than would be needed in a Phase 3 study.
For the third aim, we have applied FDG PET imaging to quantify vascular inflammation in several diseases including rheumatoid arthritis, pulmonary hypertension, COPD and aortic aneurysm (see above) all of which have an excess of unexplained cardiovascular deaths.
We also participating in prospective, multi-centre outcome-driven studies to determine the role of non-invasive imaging, biomarkers, genetic and clinical risk factors in predicting cardiovascular events.
I am the Clinical PI of a £2 million new venture – The EPSRC Mathematics in Healthcare Programme Award – with partners in Medicine, Oncology, Radiology, Biochemistry, Neuroscience and Industry and led from the Department of Mathematics and Statistics – commencing July 2016.