Key result
Lymphatic deficiency in mice increases post-MI cardiac edema and expands T2 relaxation map differences.
Why the study?
The role of cardiac lymphatics in myocardial infarction pathogenesis is unclear, prompting evaluation of lymphatic insufficiency on infarct characteristics using MRI endogenous contrast methods.
Lymphatic deficiency increases cardiac edema following myocardial infarction, which can be effectively characterized without contrast agents using a combination of TRAFF2 or TRAFF4 and T2 MRI relaxation times.
Highlights potential lymphatic targets in post-MI edema; leaves open clinical validation of non-contrast TRAFF-T2 MRI mapping.
The role of cardiac lymphatics in the pathogenesis of myocardial infarction (MI) is unclear. Lymphatic system regulates cardiac physiological processes such as edema and tissue fluid balance, which affect MI pathogenesis. Recently, MI and fibrosis have been assessed using endogenous contrast in magnetic resonance imaging (MRI) based on the relaxation along a fictitious field with rank n (RAFFn). We extended the RAFFn applications to evaluate the effects of lymphatic insufficiency on MI with comparison to longitudinal rotating frame (T 1ρ ) and T 2 relaxation times. MI was induced in transgenic (TG) mice expressing soluble decoy VEGF receptor 3 that reduces lymphatic vessel formation and their wild-type (WT) control littermates for comparison. The RAFFn relaxation times with rank 2 (T RAFF2 ), and rank 4 (T RAFF4 ), T 1ρ and T 2 were acquired at time points 0, 3, 7, 21 and 42 days after the MI at 9.4 T. Infarct sizes were determined based on T RAFF2 , T RAFF4 , T 1ρ and T 2 relaxation time maps. The area of differences (AOD) was calculated based on the MI areas determined on T 2 and T RAFF2 , T RAFF4 or T 1ρ relaxation time maps. Hematoxylin–eosin and Sirius red stained histology sections were prepared to confirm MI locations and sizes. MI was detected as increased T RAFF2 , T RAFF4 , T 1ρ and T 2 relaxation times. Infarct sizes were similar on all relaxation time maps during the experimental period. Significantly larger AOD values were found together with increased AOD values in the TG group compared to the WT group. Histology confirmed these findings. The lymphatic deficiency was found to increase cardiac edema in MI. The combination of T RAFF2 (or T RAFF4 ) and T 2 characterizes MI and edema in the myocardium in both lymphatic insufficiency and normal mice without any contrast agents.
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Ylä‐Herttuala et al. (2023) studied Myocardial infarction (n=39). Lymphatic insufficiency (sVEGFR3 expression) vs. Wild-type was evaluated on Area of difference (AOD) between T2-defined MI area and rotating frame relaxation time maps. Lymphatic deficiency in transgenic mice increased cardiac edema in myocardial infarction, resulting in significantly larger areas of difference between T2 and rotating frame relaxation time maps compared to wild-type mice.
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