## 3 Cardiovascular Disease
### Venous Thromboembolism
#### 3.4.3 Imaging Venous Thromboembolisms  
Direct MRI Thrombus Imaging  
[PERSON] et al. [133] demonstrated that it is possible exploit the intrinsic T1 properties of tissues to image thrombus with MRI. Proton binding to Fe\({}^{3+}\) within accumulating methemoglobin in thrombi produces T1 shortening leading to high signal intensity on T1-weighted images of thrombi such as in DVT. In a murine model of DVT, [PERSON] et al. assessed the longitudinal relaxation time (T1) of thrombus over a 28 day evolutionary phase of the thrombus [134]. They demonstrated that the T1 relaxation time of thrombus was shortest at 7 days following thrombus induction and returned to that of blood as the thrombus resolved (Figure 18). T1 relaxation time was related to thrombus methemoglobin formation and was a good predictor of successful thrombolysis with a cut-off point of <747 ms; with a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. In a similar experimental murine model of DVT, [PERSON] et al. assessed the feasibility of in vivo magnetization transfer contrast (MTC) and diffusion-weighted (DW) MRI for thrombus imaging [135]. They demonstrated that quantitative MTC imaging is able to differentiate between young (days 1 and 7) and old (>day 14) thrombus, while the combination of quantitative MTC and DW imaging can successfully identity thrombus between days 7 and 14 (Figure 19). Figure 18: Magnetic resonance T1 mapping of experimental venous thrombi. (**A**), MRI venography demonstrates the presence of thrombus in the murine inferior vena cava, which recanalizes over 28 days. (**B**), MSB sections of venous thrombus (T) during its resolution (yellow = red cells, red = fibrin, blue = collagen; \(\times\)200; bar, 200 μm). (**C**), Corresponding T1 maps were generated by the use of a customised program (MATLAB software, MathWorks) before importation into OSIRDX as shown. Short T1 relaxation times (ms) appear red and revert back to blood (black) as thrombus ages. (**D**), Mean T1 relaxation times (ms) of the thrombus change during its resolution (scatter plot and mean of thrombus T1 relaxation time [ms] is shown, n = 88 mice, \(p\) < 0.0001, 1-way ANOVA). Mouse procedures were performed under the Animals (Scientific Procedures) Act, 1986, UK. ANOVA indicates analysis of variance; d—day; and MSB—Martius Scarlet Blue. Reproduced with permission from [PERSON] et al., 2013 [134]. Recently, [PERSON] et al. demonstrated the feasibility of non-contrast diffusion weighted MRI for in vivo discrimination of acute (\(<\)14 days) from non-acute (\(>\)14 days) DVT [136]. In this study, 85 patients with lower limb DVT who underwent diffusion weighted MRI could be successfully differentiated based on their apparent diffusion coefficient (ADC) images. The mean ADC was higher in acute DVT than non-acute DVT (\(0.56\pm 0.17\times 10^{-3}\) vs. \(0.22\pm 0.12\times 10^{-3}\) mm\({}^{2}\)/s, \(p<0.001\)). Using \(0.32\times 10^{-3}\) mm\({}^{2}\)/s as the cut-off, the sensitivity and specificity of ADC to discriminate acute from non-acute DVT were 93% and 90%, respectively (Figure 20). Figure 19: Percentage of magnetization transfer rate (MTR) and apparent diffusion coefficient (ADC) values measured at different time points of venous thrombosis organization. The combination of the percentage of MTR (\(<\)7620%/cm\({}^{3}\)) and ADC (\(>\)0.81 \(\times\) 10 \(-\) 3 mm\({}^{2}\)/s) had a sensitivity of 87.5% (95% confidence interval [CI], 47–49) and specificity of 83.3% (95% CI, 51–97) to identify thrombus between 7 and 14 days old, when the fibrin content would be larger. Reproduced with permission from [PERSON] et al., 2013 [135]. Figure 20: A comparison between acute and non-acute DVT. Acute thrombus (first line) and non-acute thrombus (second line) were hypointense on b = 0 (**a,d**), b = 800 s/mm2 (**b,e**) image. The signal intensity was about the same for acute and non-acute thrombus, while ADC values differed greatly (**c,f**).