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Preclinical cardiac MR is challenging and time-consuming. A fast and comprehensive acquisition protocol and standardized image post-processing may improve preclinical research, reducing acquisition time, costs and variability of results. In the present study, we evaluated the feasibility of a contrast-enhanced 3D IntraGate steady-state cine sequence (ce-3D-IG-cine) with short acquisition time (11 min) for a single-shot combined characterization of left ventricle (LV) remodeling and infarct size (IS) in a mouse model of acute ischemia-reperfusion injury. Sixteen male C57BL/6N mice underwent 7T cardiac MR (Bruker, BioSpec 70/30) including optimized ce-3D-IG-cine (total scan time 11 min) at day 1, 5 and 28 after surgery. LV end-diastolic volume (EDV MR ) and ejection fraction (EF MR ) extracted from MR were compared to ones from short-axis (SA-EDV echo , SA-EF echo ) and parasternal long-axis (LA-EDV echo , LA-EF echo ) echocardiography. IS was manually and semiautomatically segmented from ce-3D-IG-cine using different standard deviation (SD +2, +3, +4, +5, +6 in respect to a reference tissue). Mice were sacrificed at day 28, immediately after imaging. IS at day 28 was compared to injury burden at histology. MR and echocardiographic morpho-functional parameters were compared, as IS from MR and histology. Bland-Altman plots were used to assess the agreement in ischemic burden segmentation. Volumetric and functional parameters measured on ce-3D-IG-cine correlated to the correspondent echocardiographic parameter (EDV MR vs SA-EDV echo : ρ = 0.813; EDV MR vs LA-EDV echo : ρ = 0.845; EF MR vs SA-EF echo ρ = 0.612; EF MR vs LA-EF echo ρ = 0.791; p < 0.001 in all cases). Manually segmented IS strongly correlated with the scar at histology (ρ = 0.904, p < 0.001). A threshold of +3SD showed the highest performance for semiautomatic assessment of IS compared to manual segmentation (ρ = 0.965, p < 0.001), with an overall reproducibility of 73%, and a peak reproducibility of 80% at day 1. The ce-3D-IG-cine sequence, manually or semiautomatically segmented using 3SD threshold, allows fast and comprehensive LV morpho-functional and structural characterization in myocardial ischemia-reperfusion injury model., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR)., Design: Cardiac magnetic resonance (CMR) techniques, including cardiac 31 P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls., Results: In GH deficient patients LV systolic function (EF%: 61 ± 1.7 vs 62.1 ± 0.8; p = .44) was not different in spite of a lower LV mass (83.2 ± 5.3 vs 145.3 ± 11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ± 0.2 vs 2.1 ± 0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ± 0.8 vs 2.3 ± 0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ± 9 vs 147.9 ± 7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients., Conclusions: GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by 1 H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with 99m Tc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T 2 and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications., Statement of Significance: The ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Up-regulation of the dystrophin-related gene utrophin represents a promising therapeutic strategy for the treatment of Duchenne Muscular Dystrophy (DMD). In order to re-program the utrophin expression level in muscle, we engineered artificial zinc finger transcription factors (ZF-ATFs) that target the utrophin 'A' promoter. We have previously shown that the ZF-ATF "Jazz", either by transgenic manipulation or by systemic adeno-associated viral delivery, induces significant rescue of muscle function in dystrophic "mdx" mice. We present the full characterization of an upgraded version of Jazz gene named "JZif1" designed to minimize any possible host immune response. JZif1 was engineered on the Zif268 gene-backbone using selective amino acid substitutions to address JZif1 to the utrophin 'A' promoter. Here, we show that JZif1 induces remarkable amelioration of the pathological phenotype in mdx mice. To investigate the molecular mechanisms underlying Jazz and JZif1 induced muscle functional rescue, we focused on utrophin related pathways. Coherently with utrophin subcellular localization and role in neuromuscular junction (NMJ) plasticity, we found that our ZF-ATFs positively impact the NMJ. We report on ZF-ATF effects on post-synaptic membranes in myogenic cell line, as well as in wild type and mdx mice. These results candidate our ZF-ATFs as novel therapeutic molecules for DMD treatment., (Copyright © 2018. Published by Elsevier B.V.)

Background/objectives: To assess the gender influence on radiation dose saving allowed by prospective ECG-triggered MDCT coronary angiography (P-MDCT-CA) in comparison with retrospective ECG-gated MDCT-CA (R-MDCT-CA). The influence of kilovoltage and body mass index on radiation dose and the impact of different parameters on image quality (IQ) and diagnostic confidence (DC), were also determined., Methods: 64-slice MDCT-CA was performed in 176 patients: 66 R-MDCT-CA and 110 P-MDCT-CA. Effective dose was determined using ImpactDose software based on Monte Carlo method. Three point scales were used to assess IQ and DC on a segmental basis., Results: Patients were divided into 4 groups according with the examination performed: group A (90 pts, coronary tree assessment with P-MDCT-CA); group B (55 pts, coronary tree assessment with R-MDCT-CA); group C (20 pts, bypass grafts assessment with P-MDCT-CA); and group D (11 pts, bypass grafts assessment with R-MDCT-CA). Effective dose was 68% lower for P-MDCT-CA than R-MDCT-CA for coronary artery studies (Gr. A=4.7 ± 1.69 mSv and Gr. B=14.9 ± 4.4 mSv; p<0.05) and 63% lower for by-pass studies. Effective dose resulted significantly higher in women than in men who underwent R-MDCT-CA; conversely, no gender impact was observed on effective dose of P-MDCT-CA. As a result, dose saving with prospective gating was more pronounced in women (73%; R-MDCT-CA:16.3 mSv, P-MDCT-CA:4.5 mSv,) than in men (60%; R-MDCT-CA:12.8 mSv, P-MDCT-CA:4.8 mSv). IQ and DC of P-MDCT-CA were better or comparable than R-MDCT-CA CONCLUSIONS: P-MDCT-CA provides at least comparable IQ and DC than R-MDCT-CA with significant dose saving. This study highlights the important advantage offered by using P-MDCT-CA in female patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: This study was performed to assess left ventricular (LV) energy metabolism and function in patients with type 1 diabetes with or without overt microvascular complications., Methods: We performed cardiac Magnetic Resonance Imaging (MRI) and (31)P spectroscopy (MRS) in 24 patients with overt microvascular complications and in 15 carefully selected patients without complications in spite of a long duration of the disease (>20 years) and matched for anthropometric features. 31 healthy subjects served as a control group., Results: Systolic function was preserved in all study subjects. Patients with overt complications showed a higher LV wall mass/end diastolic volume ratio and altered parameters of diastolic function when compared to patients without complications and to controls. They were also characterized by lower PCr/ATP ratio (a recognized marker of energy metabolism). No effect of HbA1c was detected within groups., Conclusions: In patients with type 1 diabetes 1) overt microvascular complications were associated with altered LV geometry, diastolic function and energy metabolism 2) in patients without complications and duration of disease >20 years no association with these alterations were found despite poor glycemic control. The features of this highly selected subgroup of patients demonstrated that long lasting chronic hyperglycemia per se is not sufficient to induce abnormality of cardiac energy metabolism and that additional yet to be identified (metabolic or genetic) factors must be important contributing factors., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)