Table 1.
Summary of direct thrombus-imaging studies
| Group (year) | Model | Imaging modality | Key findings |
|---|---|---|---|
| Flacke et al. [30] (2001) | Atherosclerosis in dogs | Gadolinium-diethylenetriaminepe tacetate-bis-oleate-nanoparticle magnetic resonance imaging (MRI) | -Fibrin-targeted paramagnetic nanoparticles |
| -Sensitive detection of vulnerable plaques | |||
| Johnstone et al. [36] (2001) | Intraluminal thrombus in rabbits | Contiguous cross-sectional T2 weighted MRI | -Measurement of thrombus formation after pharmacological triggering |
| -Determination of presence, location, and size of thrombus | |||
| Corti et al. [33] (2002) | Arterial thrombus in pigs | Black-blood MRI | -Detection of arterial thrombosis |
| -Potential application in determining thrombus age | |||
| Moody et al. [39] (2003) | Patients with cerebral ischemia | 3D T1-weighted direct thrombus MRI | -Identifying complicated plaques |
| -Easy to apply on commercially available scanners without additional hardware or software | |||
| Botnar et al. [37] (2004) | Acute thrombosis after plaque rupture in rabbits | Fibrin-binding gadolinium-labeled peptide, EP-1873, MRI | -Fibrin-binding contrast agents |
| -in vivo MRI of thrombosis after plaque rupture | |||
| Sirol et al. [60] (2005) | Carotid artery thrombosis in rabbits | Fibrin-binding gadolinium-labeled peptide, EP-2104R, MRI | -Fibrin-targeted contrast agents |
| -in vivo detection of chronic or organized thrombus using EP-2014R | |||
| -Discrimination of occlusive arterial thrombi from non-occlusive ones | |||
| Viereck et al. [38] (2005) | Arterial thrombosis in rabbits | Diffusion-weighted MRI | -Noninvasive in vivo detection of atherothrombosis |
| -Diagnostic tool for plaque-associated white thrombi | |||
| -Improved contrast between the thrombus and the underlying plaque | |||
| Muhlen et al. [41] (2008) | Thrombosis in mice | Single-chain antibody conjugated iron oxide microparticles MRI | -Targeting activated platelets |
| -Monitoring of thrombotic treatment | |||
| -ex vivo MRI of human carotid plaques | |||
| Overoye-Chan et al. [20] (2008) | Thrombosis in humans | Fibrin-binding gadolinium-labeled peptide, EP-2104R, MRI | -Fibrin-targeted contrast agents |
| -Detection of thrombi not normally visible in precontrast imaging | |||
| Klink et al. [61] (2010) | Carotid thrombosis in mice | Gadolinium-based paramagnetic agent, P975, MRI | -Integrin αIIbβ3-targeted (activated platelet) paramagnetic contrast agent |
| -in vivo imaging of platelet-rich acute thrombi | |||
| Weisstanner et al. [40] (2014) | Patients with acute ischemic stroke | Time-of-flight MR angiography (MRA) | -Susceptibility-weighed imaging for visualization of thrombotic material |
| -96% of success rate for thrombus detection by susceptibility-weighted imaging | |||
| -Thrombus length may not have an impact on success of endovascular reperfusion therapy in middle cerebral artery occlusions | |||
| Wen et al. [62] (2015) | Carotid artery thrombosis in mice | Virus nanoparticle MRI | -Fibrin-binding virus particles |
| -Nanoparticle shape dependency for thrombus targeting | |||
| Gale et al. [63] (2015) | Arterial thrombosis in rats | Manganese-based-fibrin-binding probe MRI | -Stable Manganese complex as a Gadolinium alternative |
| -Fibrin-targeted and equivalent thrombus enhancement to EP-2014R | |||
| Heidt et al. [43] (2016) | Pulmonary embolism in mice | Single-chain antibody conjugated iron oxide microparticles and T2-weigthted MRI | -Activated platelet-targeted agent |
| -Detection of pulmonary thromboemboli | |||
| -Increasing sensitivity of MRI for pulmonary thromboemboli | |||
| Aziz et al. [46] (2008) | Arterial thrombosis in rabbits | Fluorine-18 fluorodeoxyglucose (18FDG) positron emission tomography (PET) and computed tomography (CT) angiography | -Detection of plaque inflammation and thrombosis |
| -Feasibility study in the atherosclerosis and thrombosis that may have clinical relevance | |||
| Patel et al. [64] (2011) | Arterial thrombosis in rabbits | 18F-FDG-PET | -Monitoring pharmacological effects of ezetimibe on plaque disruption and thrombosis |
| -Plaque rupture and thrombosis are associated with inflammatory response and cholesterol crystal formation | |||
| Ciesienski et al. [48] (2013) | Carotid artery thrombosis in rats | 64Cu-fibrin-binding-probe 8 (64Cu-FBP8), DOTA-labeled probes PET | -New fibrin targeting PET probes |
| -Effective detection of an arterial thrombus | |||
| Ay et al. [65] (2014) | Mural and occlusive thrombosis in rats | 64Cu-FBP7,CB-TE2A-labeled probes PET | -Thrombus detection and therapy monitoring with tissue plasminogen activator (tPA) |
| -Detectable for both non-occlusive and occlusive thrombi | |||
| -Quantification of in vivo thrombolysis | |||
| Hara et al. [47] (2014) | Deep vein thrombosis in mice and humans | FDG-PET/CT | -Enabling the assessment of thrombus age and inflammation |
| -Detection of neutrophil-rich thrombus | |||
| Blasi et al. [49] (2014) | Thrombosis in rats | 64Cu-FBP8, NOTA-labeled probes PET | -Enhanced fibrin targeting PET probes |
| -Improved metabolic stability compared to DOTA derivative | |||
| -High thrombus-to-background ratio for imaging of thrombosis | |||
| Blasi et al. [50] (2015) | Multi-site thrombosis in rats | 64Cu-FBP8 PET/CT | -Whole-body thrombus detection |
| -Noninvasive evaluation of fibrin content in clots | |||
| -Finding different fibrin contents in arterial and venous clots | |||
| Kim et al. [7] (2013) | Carotid arterial thrombosis in mice | Gold nanoparticle microCT | -Direct thrombus imaging with gold nanoparticles |
| -Monitoring the therapeutic efficacy of thrombolysis in large sample numbers (n=118) | |||
| -Repeating CT imaging after up to 3 weeks without additional gold nanoparticles | |||
| Kim et al. [10] (2015) | Embolic ischemic stroke and carotid thrombosis in mice | Fibrin-targeted gold nanoparticle microCT | -Superior specificity of fibrin-targeted gold nanoparticles to thrombi compared to non-targeted gold nanoparticles |
| -Prompt detection and quantification of cerebral thrombi in vivo | |||
| -Reliability of thrombi imaging proficiency from huge sample numbers (n=107) | |||
| Grover et al. [55] (2015) | Venous thrombosis in mice | Gold nanoparticle microCT | -Longitudinal assessment of venous thrombus |
| -Extravasation of gold nanoparticles | |||
| -Reduced thrombus volume 7 days after induction |
DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; NOTA=1,4,7,10-triazacyclononane-1,4,7,10-triacetic acid; CB-TE2A=2,2’-(1,4,8,11-tetraazabicyclo [6.6.2] hexadecane-4,11-diyl)-diacetic acid.