| Summary: | Deep venous thrombosis (DVT) remains a major health problem. Although thrombolytic therapies are effective in recanalising the veins, restoring blood flow, preventing pulmonary embolism and post-thrombotic complications, there is still no consensus on the selection criteria for this invasive treatment. Experimental data suggest that thrombus rich in fibrin has better response to thrombolysis than red cell rich (acute phase) or collagen rich (chronic) thrombus. Thus, there is a need for a diagnostic technique that provides better information on the stage of thrombus organization in-vivo and allows identification of thrombus suitable for thrombolysis. Current imaging modalities for the diagnosis of DVT do not provide information on the biological stage of thrombus organization. Contrast venography is still considered the gold standard for the diagnosis of DVT, even though thrombi are not clearly visualized and they are indirectly detected due to alterations in blood flow. The aim of this thesis was to develop and validate new imaging methodology for the better evaluation of DVT using Magnetic Resonance Imaging (MRI). The first aim was to investigate the potential of non-contrast enhanced MRI sequences including T1 mapping, T2* mapping, Magnetization Transfer Contrast (MTC), and Apparent Diffusion Coefficients (ADC) maps for the detection of thrombus in a murine model of deep venous thrombosis. The second aim was to investigate the merit of a fibrin and macrophage specific MR contrast agent for the detection of DVT. Both fibrin and macrophages play a major role in thrombus organization. The third aim was to investigate the merits of the fibrin binding contrast agent for the guidance of thrombolysis. We also developed two new non-contrast enhanced venous spin labelling approaches in order to obtain venograms without the need of a contrast agent and thereby to improve non-invasive DVT diagnosis using MRI. In conclusion, this thesis proposes a new imaging methodology for the accurate staging of thrombus organization and the successfully detection of thrombus amenable for thrombolysis in a murine model of DVT. The translation of this technique into the clinic should have great potential to change clinical evaluation and treatment of patients with DVT.
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