Monocyte and/or macrophage infiltration of heart after myocardial infarction: MR imaging by using T1-shortening liposomes.
OBJECTIVE
To test the hypothesis that magnetic resonance (MR) imaging R1 (R1 = 1/T1) mapping after selectively labeling monocytes with a T1-shortening contrast agent in vivo would enable the quantitative measurement of their spatiotemporal kinetics in the setting of infarct healing.


METHODS
All procedures were performed in mice and were approved by the institutional committee on animal research. One hundred microliters of dual-labeled liposomes (DLLs) containing gadolinium (Gd)-diethylenetriaminepentaacetic acid (DTPA)-bis(stearylamide) and DiI dye were used to label monocytes 2 days before myocardial infarction (MI). MI was induced by occlusion of the left anterior descending coronary artery for 1 hour, followed by reperfusion. MR imaging R1 mapping of mouse hearts was performed at baseline on day -3, on day 0 before MI, and on days 1, 4, and 7 after MI. Mice without labeling were used as controls. ΔR1 was calculated as the difference in R1 between mice with labeling and those without labeling. CD68 immunohistochemistry and DiI fluorescence microscopy were used to confirm that labeled monocytes and/or macrophages infiltrated the postinfarct myocardium. Statistical analysis was performed by using two-way analysis of variance and the unpaired two-sample t test.


RESULTS
Infarct zone ΔR1 was slightly but nonsignificantly increased on day 1, maximum on day 4 (P < .05 vs all other days), and started to decrease by day 7 (P < .05 vs days -3, 0, and 1) after MI, closely reflecting the time course of monocyte and/or macrophage infiltration of the infarcted myocardium shown by prior histologic studies. Histologic results confirmed the presence and location of DLL-labeled monocytes and/or macrophages in the infarct zone on day 4 after MI.


CONCLUSIONS
R1 mapping after labeling monocytes with T1-shortening DLLs enables the measurement of post-MI monocyte and/or macrophage spatiotemporal kinetics.
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Nivedita K
NK
Naresh
Yaqin
Y
Xu
Alexander L
AL
Klibanov
Moriel H
MH
Vandsburger
Craig H
CH
Meyer
Jonathan
J
Leor
Christopher M
CM
Kramer
Brent A
BA
French
Frederick H
FH
Epstein
D000704:Analysis of Variance; D000818:Animals; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D008081:Liposomes / Q000493:pharmacokinetics*; D008264:Macrophages / Q000378:metabolism*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*
D008081:Liposomes; D019786:Gadolinium DTPA