Preclinical MRI of proinflammatory epicardial adipose tissue: Accelerated methods for simultaneous fatty acid composition and relaxation parameter mapping with relationships to tissue biomarkers.

Background: Epicardial adipose tissue (EAT) plays a central role in metabolic heart disease through local inflammatory signaling. In obesity, EAT undergoes pathological remodeling marked by increased adipocyte size, saturated fatty acids (SFAs), macrophage infiltration, and inflammatory cytokine secretion. Proton density fat fraction (PDFF), T₁, and the fatty acid composition (FAC) (the amount of SFAs, monounsaturated fatty acids [MUFAs], and polyunsaturated fatty acids [PUFAs]) are promising metrics of EAT quality, yet their role as biomarkers of proinflammatory EAT has not been established. This study presents an accelerated CMR method for simultaneous EAT FAC and T₁ mapping and evaluates their relationships with histological and cytokine markers of inflammation.

Methods: An ECG-gated inversion recovery multi-echo gradient-echo sequence with radial golden-angle sampling was developed for simultaneous FAC and T₁ mapping. A high-dimensionality patch-based low-rank reconstruction was applied to undersampled images. Phantom validation was performed using oil mixture and gadolinium phantoms, followed by in vivo imaging of mice (n=16-20/group) fed a high-fat high-sucrose diet (HFHSD), HFHSD plus the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin (HFHSD+EMPA), or a high-fat diet (HFD). PDFF, SFA fraction, MUFA fraction, PUFA fraction, R₂*, and T₁ measurements were made in EAT and subcutaneous adipose tissue (SAT). EAT FAC values were indexed to those of SAT. Ex vivo histology and cytokine assays were used to assess EAT and myocardial inflammation.

Results: Phantom validation demonstrated strong agreement between MRI-derived and reference FAC and T₁ values (r > 0.94, p < 0.05). Diet-induced changes in adipose tissue FAC were detected by MRI. HFHSD+EMPA mice had lower EAT SFA index than both HFHSD (p < 0.01) and HFD (p < 0.05) mice, and higher MUFA index (p < 0.01), PUFA index (p < 0.05), and T₁ (p < 0.05) compared HFHSD mice. EAT SFA index positively correlated with macrophage infiltration and proinflammatory cytokines, while MUFA and PUFA indexes were inversely correlated with proinflammatory cytokines. EAT T₁ negatively correlated with adipocyte hypertrophy.

Conclusion: This study developed an accelerated EAT FAC and T₁ imaging method and provides evidence that MRI-derived EAT FAC indexes and T₁ may serve as biomarkers of proinflammatory EAT by demonstrating correlations with histological and cytokine markers.