Advanced methods for quantification of infarct size in mice using three-dimensional high-field late gadolinium enhancement MRI

Abstract

Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology or relying on nondirect measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional (3D) late gadolinium enhancement MRI (3D-LGE). Myocardial T1 relaxation was quantified at 9.4 Tesla in five mice, and reproducibility was tested by repeat imaging after 5 days. In a separate set of healthy and infarcted mice (n = 8 of each), continuous T1 measurements were made following intravenous or intraperitoneal injection of a contrast agent (0.5 micromol/g gadolinium-diethylenetriamine pentaacetic acid). The time course of T1 contrast development between viable and nonviable myocardium was thereby determined, with optimal postinjection imaging windows and inversion times identified. Infarct sizes were quantified using 3D-LGE and compared with triphenyltetrazolium chloride histology on day 1 after infarction (n = 8). Baseline myocardial T1 was highly reproducible: the mean value was 952 +/- 41 ms. T1 contrast peaked earlier after intravenous injection than with intraperitoneal injection; however, contrast between viable and nonviable myocardium was comparable for both routes (P = 0.31), with adequate contrast remaining for at least 60 min postinjection. 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 noninvasively 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 before intervention with stem cells.

Late gadolinium enhancement of acute myocardial infarction in mice at 7T: Cine‐FLASH versus inversion recovery

“…Gd enhancement was visible until at least 50 minutes after injection, which is in agreement with recently published studies (5). For the IR method, with latencies after Gd injection between 30 and 50 minutes, optimal inversion times were typically between 300 and 400 msec.…”

MRI-based prediction of adverse cardiac remodeling after murine myocardial infarction

“…MRI has high accuracy in quantifying not only volumes and mass in remodeling murine heart but also infarct size (IS; Refs. 3,7,20,21,26) by the use of late gadolinium enhancement (LGE) in the acute phase (1,3,19). We therefore hypothesized that MRI-based parameters measured in the acute phase after experimental murine MI could predict the extent of delayed adverse remodeling.…”

Novel Porcine Models of Myocardial Ischemia/Infarction – Technical Progress, Modified Electrocardiograms Validating, and Future Application

“…They had validated an improved 3D MRI method to noninvasively 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 before intervention with stem cells (Bohl et al, 2009). Another study group combined the small-animal PET and MRI data to acquire quantitative in vivo insights into cardiac pathophysiology, and sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model.…”

“…Second, visual interpretation and planimetry of heart sections may be subjective in cases with poor viable/non-viable contrast due to hemoglobin residues within the necrotic regions or with TTC-induced geometric distortion of the sample. Finally, animals must be euthanized to measure injury, meaning longitudinal studies require separate groups of animals for each time point (Bohl et al, 2009). Conventional TTC staining allows the quantification of infarct size much sooner than standard histological techniques, and has been shown to be equally sensitive and specific.…”