Submitted on December 15, 2008
Revised on January 23, 2009
Accepted on February 9, 2009
Advanced Methods for Quantification of Infarct Size in Mice Using Three-Dimensional High-Field Late Gadolinium Enhancement MRI
Steffen Bohl1, Craig A Lygate2, Hannah Barnes1, Debra J Medway3, Lee-Anne Stork2, Jeanette Schulz-Menger4, Stefan Neubauer2, and Jurgen E. Schneider2*
1 British Heart Foundation Experimental MR Unit, The Wellcome Trust Centre for Human Genetics, University of Oxford
2 University of Oxford
3 The Wellcome Trust Centre for Human Genetics, University of Oxford
4 Franz Volhard Clinic
* To whom correspondence should be addressed. E-mail: jurgen.schneider{at}cardiov.ox.ac.uk.
Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology, or relying on non-direct measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional Late-Gadolinium-Enhancement MRI (3D-LGE). Myocardial T1-relaxation was quantified at 9.4 Tesla in 5 mice, and reproducibility tested by repeat imaging after five days. In a separate set of healthy and infarcted mice (n=6 of each), continuous T1-measurements were made following intravenous (IV) or intraperitoneal (IP) injection of contrast agent (0.5µmol/g Gadolinium-dTPA). The time course of T1-contrast development between viable and non-viable myocardium was thereby determined, with optimal post-injection imaging windows and inversion-times identified. Infarct sizes were quantified using 3D-LGE and compared with tetrazolium-chloride histology on day 1 after infarction (n=8). Baseline myocardial T1 was highly reproducible: mean value 952±41ms. T1-contrast peaked earlier after IV injection than with IP, however contrast between viable and non-viable myocardium was comparable for both routes (P=0.31), with adequate contrast remaining for at least 60 min post-injection. Excellent correlation was obtained between infarct sizes derived from 3D-LGE and histology (r=0.91, P=0.002), and Bland-Altman analysis indicated good agreement free from systematic bias. We have validated an improved 3D MRI method to non-invasively quantify infarct size in mice with unsurpassed spatial resolution and tissue contrast. This method is particularly suited to studies requiring early quantification of initial infarct size, for example, to measure damage prior to intervention with stem cells.
