Cheongsoo Park1,2, Eun-Hye Park3, Jongeun Kang1,4, Kiyuk Chang3, and Kwan Soo Hong1,4,5
1Korea Basic Science Institute, Cheongju, Korea, Republic of, 2The Catholic University of Korea, Seoul, Korea, Republic of, 3Seoul St. Mary’s Hospital and College of Medicine, Seoul, Korea, Republic of, 4Chungnam National University, Daejeon, Korea, Republic of, 5University of Science and Technology, Daejeon, Korea, Republic of
Synopsis
Myocardial
infarction (MI) is the major cause of sudden death in most industrialized
society. Imaging of early disease progression and investigation of relationship
between myocardial necrosis and successive inflammatory response are needed for
optimal treatment of MI. We conducted cardiac MR imaging of disease progression
in acute MI by using three different MRI methods of Gd (LGE), Mn (ME), and iron
oxide nanoparticles (MNP)-based MRI for estimation of infarcted and
inflammatory regions.Purpose
To assess
the relationship between necrosis and its inflammatory response in acute MI
using cardiac MRI.
Methods
MI was
induced by permanent ligation of the left anterior descending artery in C57BL/6
mice (n = 22). LGE (Omniscan, 0.3 mmol/kg), MEMRI (MnCl2, 0.2
mmol/kg), and MNP-MRI (5 and 10 mg/kg) were performed on 1, 2, and 3 days after
MI induction, respectively. MR imaging parameters were as follows; slice
thickness = 1 mm, field of view = 3×3 cm
2, matrix size = 256×256,
TR/TE = 73/2.7 ms, flip angle = 60°, TR/TE = R-R interval/6 ms, flip angle =
30° for MNP-MRI (24 hours delay). After all MRI examination, the hearts were
extracted for histopathology. Consecutive heart tissue sections (~5 μm) were
stained with H&E and immunohistochemistry (anti-myosin antibody for
necrosis and anti-CD68 antibody for macrophages).
Enhanced (or contrast) size on MR images was analyzed by area- and sector-based
approaches by using Segment (Medviso) and ImageJ (NIH). To prevent observer
bias, enhanced size was calculated by Otsu’s thresholding method.
Results
Representative
images are presented in Figure 1. Inflammatory area by MNP-MRI was higher than
infarcted areas by LGE and MEMRI (Figure 2). Measured contrast sizes of LGE,
MEMRI, and MNP-MRI were 40.5±11.5%, 46.5±14.1%, and 58.6±10.6% in area-based
method (Figure 2A), and 45.2±15.0%, 45.8±16.9%, and 58.7±14.2% (Figure 2B),
respectively. Infarcted and inflammatory regions in MR images were consistent
with H&E stain and immunohistochemistry.
Discussion
and Conclusion
Our study is the
first to use the three different MRI methods for imaging necrosis and
inflammation in the same animals during acute MI phase. Cellular inflammatory
response was strongly correlated with myocardial damage and associated with poor
functional outcome after MI.1 Deftereos et al. presented that the infarct
size on LGE was well correlated with CK-MB (necrosis) and neutrophil
(inflammation).2 Further studies are necessary in order to better
understand the underlying mechanism of the disease progression in the acute MI.
Therefore it is important to develop the cellular and molecular imaging techniques
to examine the myocardial necrosis and the consequent inflammatory response.
Acknowledgements
No acknowledgement found.References
1. van der Laan AM,
Hirsch A, Robbers LF, et al. A proinflammatory monocyte response is associated
with myocardial injury and impaired functional outcome in patients with
ST-segment elevation myocardial infarction: monocytes and myocardial
infarction. Am Heart J 2012;163:57–65.
2. Deftereos S,
Giannopoulos G, Angelidis C, et al. Anti-Inflammatory Treatment With Colchicine
in Acute Myocardial Infarction: A Pilot Study. Circulation
2015;132(15):1395-403.