In vivo evaluation of a hybrid nanoparticle for molecular imaging of amyloid aggregation

International audienceAmyloid-β (Aβ) fibrillization is described as a central event in the pathogenesis of Alzheimer’s disease (AD). Amyloid imaging is expected to play a pivotal role in early and differential diagnosis of dementias, and in the evaluation of anti-Aβ treatments. Luminescent conjugated oligothiophenes (LCO) have been proposed as optical biomarkers of protein fibrillation [1]. In this paper, we evaluated a fluorescent magnetic hybrid nanoprobe (HNP5011), based on gadolinium fluoride nanoparticles functionalized with luminescent conjugated polythiophenes moieties (Fig. 1). The aim of this study was to investigate its potential for molecular imaging in a rat model bearing intracerebral pre-aggregated Aβ peptides

Contrast-enhanced ultrasound: a new method for TIPS follow-up

International audienc

Contrast-enhanced ultrasound: a new method for TIPS follow-up

International audienc

INFLAM - INFLAMmation in Brain and Vessels with Iron Nanoparticles and Cell Trafficking: A Multiscale Approach of Tissue Microenvironment, Iron Nanostructure and Iron Biotransformation

International audienceBackground: Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke. Contribution: We report here contributions to the field of inflammation imaging with USPIO-enhanced MRI. The goal was to investigate the life cycle of USPIOs in the body, and how the MRI signal has been impacted during their bio-interactions and bioprocessing. Those mechanisms were applied to pre-clinical longitudinal studies of inflammation in atherosclerosis and at the acute stage of ischemic stroke thus allowing the monitoring of treatment effects. Conclusion: This review presents the contribution of the collaborative research project under the "TecSan" grant from the French Research Agency (ANR) as well as pre-clinical and clinical perspectives of USPIO's inflammation MRI in atherosclerosis and stroke. (C) 2018 Published by Elsevier Masson SAS on behalf of AGBM

Effects of a TAFI-inhibitor combined with a suboptimal dose of rtPA in a murine thromboembolic model of stroke

International audienceBackground: Since thrombolysis is the only approved intervention for ischemic stroke, improving its efficacy and safety is a therapeutic aim of considerable interest. The activated form of thrombin activatable fibrinolysis inhibitor (TAFI) has antifibrinolytic effects, and inhibition of TAFI might thus favor recanalization. The present study compared efficacy between TAFI inhibition alone and TAFI inhibition in combination with rtPA at a suboptimal dose, in a murine model of thromboembolic stroke. Methods: Focal ischemia was induced in mice by thrombin injection in the middle cerebral artery. Animals were placed within the magnet immediately after surgery for baseline MRI (H0). MRI examination comprised diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and T2-weighted imaging (T2-WI). Animals were randomly assigned to 1 of 5 treatment groups: saline, rtPA 5 mg/kg (tPA5: suboptimal or low dose), rtPA 10 mg/kg (tPA10: standard dose), TAFI-I 100 mg/kg (TAFI-I), and rtPA 5 mg/kg + TAFI-I 100 mg/kg (tPA5 + TAFI-I). Treatments were administered inside the magnet, via a catheter placed in the tail vein, using a power injector, as 10% bolus and 90% infusion over a period of 20 min. MRI examination was repeated at 3 h (H3) and 24 h (H24) after surgery. Therapeutic benefit was evaluated by: (1) improvement of reperfusion and (2) reduction in final lesion size. Microhemorrhages were assessed as black spots on T2-WI at H24. Animals were sacrificed after the last MR examination. The surgeon and all investigators were blinded to treatment allocation. Results: A total of 104 mice were operated on. Forty four of these were excluded from the study and 27 from the analysis, according to a priori defined criteria (no lesion or no mismatch), leading to the following distribution: saline (n = 6), tPA5 (n = 8), tPA10 (n = 7), TAFI-I (n = 7), and TAFI-I + tPA5 (n = 5). Standard-dose rtPA treatment (tPA10) significantly improved lesion regression between H0 and H24 compared to saline (-57 ± 18% vs. -36 ± 21%, p = 0.03), which treatment with rtPA5 or TAFI-I alone did not. On the other hand, combined treatment with tPA5 + TAFI-I showed only a trend toward lesion regression (-49 ± 26%), similarly to treatment with tPA10, but not significantly different from saline (p = 0.46). Nine animals showed microhemorrhage on T2-WI at H24. These animals were evenly distributed between groups. Conclusions: The present study showed that the combination of TAFI-I with a suboptimal dose of rtPA is not as effective as the standard dose of rtPA, while TAFI inhibition alone is not effective at all. The thromboembolic model is of particular interest in assessing rtPA association to improve thrombolysis, especially when coupled with longitudinal MRI assessment