Two days after myocardial infarction (MI), the infarct consists mostly on necrotic tissue, and the myocardium is transformed through granulation tissue to scar in two weeks after the onset of ischemia in mice. In the current work, we determined and optimized cardiovascular magnetic resonance (CMR) methods for the detection of MI size during the scar formation without contrast agents in mice. We characterized MI and remote areas with rotating frame relaxation time mapping including relaxation along fictitious field in nth rotating frame (RAFFn), T1ρ and T2 relaxation time mappings at 1, 3, 7, and 21 days after MI. These results were compared to late gadolinium enhancement (LGE) and Sirius Red-stained histology sections, which were obtained at day 21 after MI. All relaxation time maps showed significant differences in relaxation time between the MI and remote area. Areas of increased signal intensities after gadolinium injection and areas with increased TRAFF2 relaxation time were highly correlated with the MI area determined from Sirius Red-stained histology sections (LGE: R2 = 0.92, P < 0.01, TRAFF2: R2 = 0.95, P < 0.001). Infarct area determined based on T1ρ relaxation time correlated highly with Sirius Red histology sections (R2 = 0.97, P < 0.01). The smallest overestimation of the LGE-defined MI area was obtained for TRAFF2 (5.6 ± 4.2%) while for T1ρ overestimation percentage was > 9% depending on T1ρ pulse power. T1ρ and TRAFF2 relaxation time maps can be used to determine accurately MI area at various time points in the mouse heart. Determination of MI size based on TRAFF2 relaxation time maps could be performed without contrast agents, unlike LGE, and with lower specific absorption rate compared to on-resonance T1ρ relaxation time mapping.

Purpose of Review Cardiovascular diseases are the leading cause of deaths worldwide. Many complex cellular and molecular pathways lead to myocardial remodeling after ischemic insults. Anatomy, function, and viability of the myocardium can be assessed by modern medical imaging techniques by both visualizing and quantifying damages. Novel imaging techniques aim for a precise and accurate visualization of the myocardium and for the detection of alternations at the molecular level. Recent Findings Magnetic resonance imaging assesses anatomy, function, and tissue characterization of the myocardium non-invasively with high spatial resolution, sensitivity, and specificity. Using hyperpolarized magnetic resonance imaging, molecular and metabolic conditions can be assessed non-invasively. Single photon-emission tomography and positron-emission tomography are the most sensitive techniques to detect biological processes in the myocardium. Cardiac perfusion, metabolism, and viability are the most common clinical targets. In addition, molecular-targeted imaging of biological processes involved in heart failure, such as myocardial innervation, inflammation, and extracellular matrix remodeling, is feasible. Summary Novel imaging techniques can provide a precise and accurate visualization of the myocardium and for the detection of alternations at molecular level.

The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic β-cell proliferation. Altered expression of a neighboring gene, CDKN2B, has been also recognized to correlate with obesity and hepatic steatosis in people carrying the risk SNPs. In the present study, we investigated the impact of 9p21.3 on obesity accompanied by hyperlipidemia in mice carrying a deletion of the murine ortholog for the 9p21.3 (Chr4^Δ70/Δ70) risk locus in hyperlipidemic Ldlr^−/−ApoB^100/100 background. The Chr4^Δ70/Δ70 mice showed decreased mRNA expression of insulin receptors in white adipose tissue already at a young age, which developed into insulin resistance and obesity by aging. In addition, the Sirt1-Ppargc1a-Ucp2 pathway was downregulated together with the expression of Cdkn2b, specifically in the white adipose tissue in Chr4^Δ70/Δ70 mice. These results suggest that the 9p21.3 locus, ANRIL lncRNA, and their murine orthologues may regulate the key energy metabolism pathways in a white adipose tissue-specific manner in the presence of hypercholesterolemia, thus contributing to the pathogenesis of metabolic syndrome.

Aims: The aim of this study was to develop an ultra-short echo time 3D magnetic resonance imaging (MRI) method for imaging subacute myocardial infarction (MI) quantitatively and in an accelerated way. Here, we present novel 3D T1- and T1ρ-weighted Multi-Band SWeep Imaging with Fourier Transform and Compressed Sensing (MB-SWIFT-CS) imaging of subacute MI in mice hearts ex vivo. Methods and results: Relaxation time–weighted and under-sampled 3D MB-SWIFT-CS MRI were tested with manganese chloride (MnCl2) phantom and mice MI model. MI was induced in C57BL mice, and the hearts were collected 7 days after MI and then fixated. The hearts were imaged with T1 and adiabatic T1ρ relaxation time–weighted 3D MB-SWIFT-CS MRI, and the contrast-weighted image series were estimated with a locally low-rank regularized subspace constrained reconstruction. The quantitative parameter maps, T1 and T1ρ, were then obtained by performing non-linear least squares signal fitting on the image estimates. For comparison, the hearts were also imaged using 2D fast spin echo-based T2 and T1ρ mapping methods. The relaxation rates varied linearly with the MnCl2 concentration, and the T1 and T1ρ relaxation time values were elevated in the damaged areas. The ischaemic areas could be observed visually in the 3D T1, 3D T1ρ, and 2D MRI maps. The scar tissue formation in the anterior wall of the left ventricle and inflammation in the septum were confirmed by histology, which is in line with the results of MRI. Conclusion: MI with early fibrosis, increased inflammatory activity, and interstitial oedema were determined simultaneously with T1 and T1ρ relaxation time constants within the myocardium by using the 3D MB-SWIFT-CS method, allowing quantitative isotropic 3D assessment of the entire myocardium.

Cardiovascular diseases are the leading cause of death worldwide due to population growth and aging. Myocardial infarct is one of the most crucial cardiovascular diseases. Acute myocardial infarct is conventionally imaged with magnetic resonance imaging (MRI) with T₂ mapping due to its sensitivity related to the correlation times of edema and free water molecules. Chronic myocardial infarction, which contains fibrosis and scar tissue, is conventionally imaged with MRI by using contrast agents since contrast agent washout from fibrosis and scar tissue is delayed compared to myocardium. Rotating frame relaxation times T_1ρ and T_2ρ mappings were developed to provide robust measurements with relatively wide B₁ and B₀ ranges for these quantities. Since rotating frame methods are sensitive to slow molecular motions, these methods owe potential to characterize both acute and chronic myocardial infarctions. In this study, rotating frame relaxation time mappings were applied to image acute (2 h) and subchronic (7 days after occlusion) myocardial infarcts in in vivo and ex vivo mouse models without using contrast agents. The in vivo imaging protocol contained adiabatic T_1ρ and adiabatic T_2ρ, both with hyperbolic secant (HS) 1 and 4 pulses, continuous wave T_1ρ and conventional T₂, together with cine imaging. Mice were imaged 2 h and 7 days after myocardial infarction. Mice were sacrificed at the 2‐h or 7‐day time point. Ex vivo measurements contained adiabatic T_1ρ and adiabatic T_2ρ with HS1 and HS4 pulses, continuous wave T_1ρ, T₁, and T₂. After MRI studies, mouse hearts were fixed, and myocardial infarcts were verified using dystrophin and hematoxylin and eosin histology stainings. A clear difference between infarcted and normal myocardium was visible at the 2‐h time point in rotating frame relaxation time mapping. Relative relaxation time difference in adiabatic T_2ρ with HS4 pulse showed the significant differences between MI and control hearts in vivo. In addition, the results of adiabatic T_1ρ with both HS1 and HS4 pulses and continuous wave T_1ρ measurements showed significant differences between MI and control hearts at both time points in both in vivo and ex vivo measurements. This study shows that rotating frame relaxation time mappings have the potential to be noninvasive MR diagnostic markers for acute and subchronic myocardial infarcts.