Aim of the PhD Project:
We aim in investigating the merits of non-contrast T1rho and magnetisation transfer (MT) MRI protocols coupled with molecular imaging of collagen, using targeted imaging probes, to quantify thrombus fibrosis, to better characterise the structure and age of venous thrombus and provide ‘virtual histology’ in an experimental animal model and in man. Ultimately, we want to guide thrombus treatment using non-invasive imaging.
Project Description / Background:
Deep vein thrombosis (DVT) affects 1 in 1000 people. Its sequelae include post-thrombotic syndrome (PTS), which affects up to 75% of patients within 5 years and is characterised by persistent pain, swelling and ulceration. Thrombolysis can reduce PTS by a third and is attempted in patients with an iliofemoral DVT and symptom onset of <3weeks. Determining age and thrombus structure by history alone is, however, subjective and there are no established methods to quantify the abundance of extracellular matrix proteins, which determines the response to lysis. This treatment is therefore only effective in ~60% of patients, which unnecessarily exposes some to haemorrhagic side effects.
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.
Therefore, we hypothesise that quantitative imaging of collagen using MRI will improve characterisation of the structure of a venous thrombus and help predict the response to lytic treatment in an experimental model of thrombosis and patients scheduled for endovascular treatment
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’.
This project is ideal for a student with a background in biology, chemistry or biomedical sciences.