1st supervisor: Alkystis Phinikaridou, King’s College London
2nd supervisor: Rene Botnar, King’s College London
Deep vein thrombosis (DVT) affects 1-2% of the population in the UK and is a significant cause of morbidity and mortality. Approximately 30% of patients with DVT develop pulmonary embolism (PE), of which 10% die; while 50% develop post-thrombotic syndrome (PTS) characterised by pain, swelling and chronic ulceration. PTS is associated with a reduced quality of life and causes a substantial financial burden to the NHS (over £1billion/year). In particular, patients who have an iliofemoral DVT are at greater risk of PTS, which has led to a drive for treatment with aggressive removal using thrombolysis. A recent Cochrane Review has suggested that this treatment could reduce the incidence PTS by up to a third. Uptake of the use of thrombolytic therapy has, however, been tempered by of the risk of serious bleeding. The time interval between the onset of symptoms and effective thrombolysis is also unclear and even within the accepted 14-21day cut-off point, ‘successful’ lysis will only be achieved in ~60% of patients.
Thrombus resolution occurs through a natural process of organisation involving the replacement of fibrin with collagen and recanalisation of the vein. Only acute thrombi are considered susceptible for lysis, as they are fibrin-rich; while older/chronic thrombi are collagenous and therefore resistant to plasmin-mediated degradation. Determining the composition of the thrombus and specifically, the abundance of collagen using a non-invasive method would help to identify which thrombi would be unsusceptible to lytic therapy.
We have extensive experience in developing multi-sequence magnetic resonance imaging (MRI) protocols to characterise the biological composition of venous thrombus in vivo. Our sequences include T1 mapping, magnetisation transfer (MT), and diffusion weighting (DW), and require no use of contrast agent. We also have extensive experience in using targeted probes to quantify specific proteins, including fibrin, that is present in venous thrombus. Importantly, building on our preclinical work we have recently completed the first in-man study that tested the predictive value of multi-sequence thrombus imaging in detecting thrombus that responds to lytic treatment, which was funded by a BHF Research Grant (PG/15/89/31793). To compliment and advance our research, we have recently developed a new (T1rho) MRI protocol, improved a magnetisation transfer MRI protocol, optimised the use of a commercially available collagen I-binding probe and identified peptides that bind to collagen III to quantify thrombus fibrosis, in order to better characterise the structure of a thrombus and provide ‘virtual histology’.
Figure 1: In vivo MRI protocols and ex vivo histological quantification of the collagen content of venous thrombus in a murine model.
Figure 2: Predictability of lysis based on MRI multi-sequence thrombus characterisation in man.