University of Oulu

Ylä-Herttuala, E., Vuorio, T., Kettunen, S. et al. Lymphatic insufficiency leads to distinct myocardial infarct content assessed by magnetic resonance TRAFFn, T1ρ and T2 relaxation times. Sci Rep 13, 1579 (2023).

Lymphatic insufficiency leads to distinct myocardial infarct content assessed by magnetic resonance TRAFFn, T and T₂ relaxation times

Saved in:
Author: Ylä-Herttuala, Elias1,2; Vuorio, Taina1; Kettunen, Sanna1;
Organizations: 1A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
2Clinical Imaging Center, Kuopio University Hospital, Kuopio, Finland
3Heart Center and Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland
4Research Unit of Medical Imaging, Physics and Technology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland
5Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2023
Publish Date: 2023-07-13


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) and T₂ 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 (TRAFF2), and rank 4 (TRAFF4), T and T₂ 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 TRAFF2, TRAFF4, T and T₂ relaxation time maps. The area of differences (AOD) was calculated based on the MI areas determined on T₂ and TRAFF2, TRAFF4 or T relaxation time maps. Hematoxylin–eosin and Sirius red stained histology sections were prepared to confirm MI locations and sizes. MI was detected as increased TRAFF2, TRAFF4, T and T₂ 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 TRAFF2 (or TRAFF4) and T₂ characterizes MI and edema in the myocardium in both lymphatic insufficiency and normal mice without any contrast agents.

see all

Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 13
Issue: 1
Article number: 1579
DOI: 10.1038/s41598-023-28219-6
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
3121 General medicine, internal medicine and other clinical medicine
Funding: This study was supported by grants from Doctoral Program of Molecular Medicine, Academy of Finland, Finnish Foundation for Cardiovascular Research, Instrumentarium Research Foundation, Veritas Foundation, Ida Montin Foundation, Aarne and Aili Turunen Foundation, Antti and Tyyne Soininen Foundation, Kuopio University Foundation, and Finnish Cultural Foundation.
Copyright information: © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit