CC chemokine CCL5 plays a central role impacting infarct size and post-infarction heart failure in mice

Aims The chemokine CCL5 plays a critical role as neutrophil and macrophage activator do in atherosclerosis and myocardial infarction. Thus, we investigated whether the treatment with a neutralizing monoclonal antibody (mAb) to mouse CCL5 would provide therapeutic benefit when provoking a coronary-associated ischaemic event. Methods and Results C57Bl/6 mice were submitted to left coronary artery permanent ligature. Then, various parameters were monitored for up to 21 days. At5 min and 3days after coronary occlusion, mice received one intravenous injection of the rat anti-mouse CCL5 mAb or isotype IgG control. Infarct size was assessed histologically and by measuring serum cardiac troponin I levels. Kinetics of CCL5 tissue expression, leucocyte infiltration, matrix metalloproteinase (MMP) levels, and collagen deposition were histologically assessed. Serum chemokine levels were measured by enzyme-linked immunosorbent assay. Cardiac function and dimensions were assessed by magnetic resonance imaging (MRI). Chronic ischaemia increased both circulating and intracardiac levels of CCL5. At 24 h, treatment with the anti-CCL5 mAb resulted in a smaller infarct size and reduced circulating levels of chemokines. This effect was associated with reduction of neutrophil and macrophage infiltration within the infarcted myocardium. After 3 days of chronic ischaemia, anti-CCL5 mAb treatment reduced cardiac MMP-9. At 7 days, collagen content was significantly lower. At 21 days, neutralizing CCL5 improved mouse survival, cardiac myocyte size, and cardiac function. Conclusion Treatment with anti-CCL5 mAb significantly reduced both infarct size and post-infarction heart failure in a mouse model of chronic cardiac ischaemia. Cardioprotective effects were associated with the reduction of leucocyte recruitment within infarcted heart

Free-Breathing Diffusion Tensor Imaging and Tractography of the Human Heart in Healthy Volunteers Using Wavelet-Based Image Fusion

International audienceFree-breathing cardiac diffusion tensor imaging (DTI) is a promising but challenging technique for the study of fiber structures of the human heart in vivo. This work proposes a clinically compatible and robust technique to provide three-dimensional (3-D) fiber architecture properties of the human heart. To this end, 10 short-axis slices were acquired across the entire heart using a multiple shifted trigger delay (TD) strategy under free breathing conditions. Interscan motion was first corrected automatically using a nonrigid registration method. Then, two post-processing schemes were optimized and compared: an algorithm based on principal component analysis (PCA) filtering and temporal maximum intensity projection (TMIP), and an algorithm that uses the wavelet-based image fusion (WIF) method. The two methods were applied to the registered diffusion-weighted (DW) images to cope with intrascan motion-induced signal loss. The tensor fields were finally calculated, from which fractional anisotropy (FA), mean diffusivity (MD), and 3-D fiber tracts were derived and compared. The results show that the comparison of the FA values (FA(PCATMIP) = 0.45 ±0.10, FA(WIF) = 0.42 ±0.05, P=0.06) showed no significant difference, while the MD values ( MD(PCATMIP)=0.83 ±0.12×10(-3) mm (2)/s, MD(WIF)=0.74±0.05×10(-3) mm (2)/s, P=0.028) were significantly different. Improved helix angle variations through the myocardium wall reflecting the rotation characteristic of cardiac fibers were observed with WIF. This study demonstrates that the combination of multiple shifted TD acquisitions and dedicated post-processing makes it feasible to retrieve in vivo cardiac tractographies from free-breathing DTI acquisitions. The substantial improvements were observed using the WIF method instead of the previously published PCATMIP technique

Intravoxel Incoherent Motion applied to Cardiac diffusion weighted MRI using breath-hold acquisitions in healthy volunteers

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In vivo free-breathing DTI and IVIM of the whole human heart using a real-time slice-followed SE-EPI navigator-based sequence: A reproducibility study in healthy volunteers

International audienceIn this study, we proposed an efficient free-breathing strategy for rapid and improved cardiac diffusion-weighted imaging (DWI) acquisition using a single-shot spin-echo echo planar imaging (SE-EPI) sequence. Methods: A real-time slice-following technique during free-breathing was combined with a sliding acquisition-window strategy prior Principal Component Analysis temporal Maximum Intensity Projection (PCAtMIP) postprocessing of in-plane co-registered diffusion-weighted images. This methodology was applied to 10 volunteers to quantify the performance of the motion correction technique and the reproducibility of diffusion parameters. Results: The slice-following technique offers a powerful head–foot respiratory motion management solution for SE-EPI cDWI with the advantage of a 100% duty cycle scanning efficiency. The level of co-registration was further improved using nonrigid motion corrections and was evaluated with a co-registration index. Vascular fraction f and the diffusion coefficients D and D* were determined to be 0.122 ± 0.013, 1.41 ± 0.09 × 10−3 mm2/s and 43.6 ± 9.2 × 10−3 mm2/s, respectively. From the multidirectional dataset, the measured mean diffusivity was 1.72 ± 0.09 × 10−3 mm2/s and the fractional anisotropy was 0.36 ± 0.02. Conclusion: The slice-following DWI SE-EPI sequence is a promising solution for clinical implementation, offering a robust improved workflow for further evaluation of DWI in cardiology. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc

In vivo cardiac diffusion tensor imaging in free-breathing conditions

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Quantitative investigation of cardiac motion effects on in vivo diffusion tensor parameters: a simulation study

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