Ultra high field MRI for the characterization of murine models of cardiovascular diseases

With the advent of transgenic and gene knockout technologies, rodents have become a cornerstone of cardiovascular research. However, accurate in vivo cardiac characterization of small animals remains challenging. In recent years, cardiac MRI has evolved to become an essential tool for experimental imaging, with progressive development of magnets operating at increasingly high field strength. In this work, we studied MRI techniques at 11.7T in mouse models of surgically induced hypertrophic and ischaemic cardiomyopathy and in an original mouse model of autoimmune cardiomyopathy. We showed that Ultra High Field MRI allows to refine characterization of such models, thanks to its great accuracy, its reproducibility and strong ability to provide specific informations on global and regional function, viability or vascular parameters. These data concur to demonstrate that this modality may provide key insights into mechanisms underlying cardiovascular diseases and indentification of new therapeutic targets.(MOTR - Sciences de la motricité) -- UCL, 201

Variability of Mouse Left Ventricular Function Assessment by 11.7 Tesla MRI.

We studied intraobserver (n = 24), interobserver (n = 24) and interexperiment (n = 12) reproducibility of left ventricular (LV) mass and volume measurements in mice using an 11.7 T MRI system. The LV systolic function was assessed with a short-axis FLASH-cine sequence in 29 mice, including animals having undergone transverse aortic constriction. Bland-Altman and regression analysis were used to compare the different data sets. Reproducibility was excellent for the LV mass and end-diastolic volume (coefficient of variability (CoV) between 5.4 and 11.8 %), good for end-systolic volume (CoV 15.2-19.4 %) and moderate for stroke volume and ejection fraction (CoV 14.7-20.9 %). We found an excellent correlation between LV mass determined by MRI and ex vivo morphometric data (r = 0.92). In conclusion, LV systolic function can be assessed on an 11.7 T MRI scanner with high reproducibility for most parameters, as needed in longitudinal studies. However, data should be interpreted taking into account the moderate reproducibility of small volumes

High field magnetic resonance imaging of rodents in cardiovascular research.

Transgenic and gene knockout rodent models are primordial to study pathophysiological processes in cardiovascular research. Over time, cardiac MRI has become a gold standard for in vivo evaluation of such models. Technical advances have led to the development of magnets with increasingly high field strength, allowing specific investigation of cardiac anatomy, global and regional function, viability, perfusion or vascular parameters. The aim of this report is to provide a review of the various sequences and techniques available to image mice on 7-11.7 T magnets and relevant to the clinical setting in humans. Specific technical aspects due to the rise of the magnetic field are also discussed

Prospective cardiac MRI for the analysis of biventricular function in children undergoing cancer treatments

BACKGROUND: Cardiotoxicity is one of the most serious long-term complications in childhood cancer survivors. Measurement of the left ventricular ejection and shortening fraction remains the most common screening tool for cardiac systolic dysfunction. However, M-mode echocardiography can be viewed as a crude approach as refined strategies are now available. The aim of this prospective study was to determine the role of cardiac MRI in the detection of subclinical left or right ventricular dysfunction as well as the prevalence of myocardial scaring in patients undergoing cancer treatments. PROCEDURE: Eighty-one children were enrolled in a pre-chemotherapy and then in a yearly protocol including a: (i) clinical evaluation; (ii) laboratory evaluation; (iii) electrocardiogram; (iv) echocardiogram; and (v) a cardiac magnetic resonance imaging (cMRI). RESULTS: Early left ventricular systolic dysfunction was only detected in two patients. The entire cohort presented a significant increase of the left atrial volume as measured by cMRI. This finding correlated with the total cumulative dose of anthracyclines (r = 0.34; P < 0.05) and the mean left ventricular radiation dose (r = 0.86; P < 0.05). We also observed a mild increase of myocardial scaring, similarly correlated to the radiation dose (r = 0.85; P < 0.05). CONCLUSIONS: Screening tools for late-onset cardiomyopathy secondary to cancer treatment are lacking. Our findings support the use of cMRI for the evaluation of the left atrial volume, as an early marker of diastolic dysfunction, and myocardial delayed enhancement, as a marker of myocardial fibrosis and scaring. Longer follow-up and larger studies are still needed to better define the role of cMRI in the evaluation of childhood cancer survivor

Toll-like receptor (TLR)2 and TLR3 synergy and cross-inhibition in murine myeloid dendritic cells.

Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs) and in the induction of immune responses. Few studies have been devoted to address the impact of TLR2 (a fully MyD88-dependent receptor) and TLR3 (a fully TRIF-dependent receptor) co-activation on DC functions, especially in the mouse system. Using canonical agonists, we show that TLR2 acts in concert with TLR3 to induce the synthesis of inflammatory cytokines (TNF-alpha, IL-6), of some IL-12 family members (IL-12p40, IL-12p23, IL-27p28) and of the Notch ligand Delta-4 by mouse DCs. In contrast, TLR2 interferes with the TLR3-induced expression of type I interferon stimulated genes (MIG/CXCL9, IP-10/CXCL10, GARG39) and IL-12p35. We also report that TLR2 cooperates with TLR3 to enhance the DC-mediated production of IFN-gamma by Natural Killer cells and by conventional Ag-specific T lymphocytes. To conclude, our data support the existence of TLR2 and TLR3 synergy and cross-inhibition in DCs that could be important to strengthen immune responses during infection.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe