Multifunctional MR monitoring of the healing process after myocardial infarction.

Abstract

Healing of the myocardium after infarction comprises a variety of local adaptive processes which contribute to the functional outcome after the insult. Therefore, we aimed to establish a setting for concomitant assessment of regional alterations in contractile function, morphology, and immunological state to gain prognostic information on cardiac recovery after infarction. For this, mice were subjected to myocardial ischemia/reperfusion (I/R) and monitored for 28 days by cine MRI, T2 mapping, late gadolinium enhancement (LGE), and (19)F MRI. T2 values were calculated from gated multi-echo sequences. (19)F-loaded nanoparticles were injected intravenously for labelling circulating monocytes and making them detectable by (19)F MRI. In-house developed software was used for regional analysis of cine loops, T2 maps, LGE, and (19)F images to correlate local wall movement, tissue damage as well as monocyte recruitment over up to 200 sectors covering the left ventricle. This enabled us to evaluate simultaneously zonal cardiac necrosis, oedema, and inflammation patterns together with sectional fractional shortening (FS) and global myocardial function. Oedema, indicated by a rise in T2, showed a slightly better correlation with FS than LGE. Regional T2 values increased from 19 ms to above 30 ms after I/R. In the course of the healing process oedema resolved within 28 days, while myocardial function recovered. Infiltrating monocytes could be quantitatively tracked by (19)F MRI, as validated by flow cytometry. Furthermore, (19)F MRI proved to yield valuable insight on the outcome of myocardial infarction in a transgenic mouse model. In conclusion, our approach permits a comprehensive surveillance of key processes involved in myocardial healing providing independent and complementary information for individual prognosis.