Quantitative T 2 * assessment of acute and chronic myocardial ischemia/reperfusion injury in mice

Abstract

ObjectImaging of myocardial infarct composition is essential to assess efficacy of emerging therapeutics. T2* mapping has the potential to image myocardial hemorrhage and fibrosis by virtue of its short T2*. We aimed to quantify T2* in acute and chronic myocardial ischemia/reperfusion (I/R) injury in mice.Materials and methodsI/R-injury was induced in C57BL/6 mice (n = 9). Sham-operated mice (n = 8) served as controls. MRI was performed at baseline, and 1, 7 and 28 days after surgery. MRI at 9.4 T consisted of Cine, T2* mapping and late-gadolinium-enhancement (LGE). Mice (n = 6) were histologically assessed for hemorrhage and collagen in the fibrotic scar.ResultsBaseline T2* values were 17.1 ± 2.0 ms. At day 1, LGE displayed a homogeneous infarct enhancement. T2* in infarct (12.0 ± 1.1 ms) and remote myocardium (13.9 ± 0.8 ms) was lower than at baseline. On days 7 and 28, LGE was heterogeneous. T2* in the infarct decreased to 7.9 ± 0.7 and 6.4 ± 0.7 ms, whereas T2* values in the remote myocardium were 14.2 ± 1.1 and 15.6 ± 1.0 ms. Histology revealed deposition of iron and collagen in parallel with decreased T2*.ConclusionT2* values are dynamic during infarct development and decrease significantly during scar maturation. In the acute phase, T2* values in infarcted myocardium differ significantly from those in the chronic phase. T2* mapping was able to confirm the presence of a chronic infarction in cases where LGE was inconclusive. Hence, T2* may be used to discriminate between acute and chronic infarctions.

High field magnetic resonance imaging of rodents in cardiovascular research

“…They showed that T2*-weighted images could be used to discriminate between acute and chronic phase of MI, as a reduction of T2* was observed with infarct age, probably because of the presence of iron [3]. Potential interest of such sequence in mouse models of chronic iron overload has also been assessed at field \7 T [110], but still need further validation at HF, as T2* is very sensitive to large scale magnetic field homogeneities, and may be difficult to measure in case of high iron concentration, as signal decay may become rapid [130].…”

Myocardial T2* Mapping with Ultrahigh Field Magnetic Resonance: Physics and Frontier Applications

“…This could provide new diagnostic means to a large group of patients excluded from contrast agent injections due to renal insufficiencies. A study employing a mouse myocardial ischemia/reperfusion model has provided first insights into in vivo quantification of T 2 * changes in the mouse myocardium in relation to tissue damage [16]. Local decrease of T 2 * was found in the infarct * Mapping at Ultrahigh Field and HCM patients (right).…”

“…T 2 * mapping has been shown to be capable of detecting myocardial ischemia caused by coronary artery stenosis [4], to reveal myocardial perfusion deficits under pharmacological stress [5][6][7][8][9][10], to study endothelial function [11] or to assess breathing maneuver-dependent oxygenation changes in the myocardium [12][13][14][15]. Preclinical studies have also demonstrated the potential of T 2 * mapping to detect structural changes in the infarcted heart muscle and even to distinguish between focal and diffuse fibrosis [16][17][18]. In clinical application T 2 * mapping is the method of choice for quantification of myocardial iron content, an essential parameter for guiding therapy in patients with myocardial iron overload [19][20][21][22][23].…”

Endogenous contrast MRI of cardiac fibrosis: Beyond late gadolinium enhancement

“…In addition, it has been shown in an in vivo mouse model that the T 2 * value decreases during the initial weeks, when the infarction progresses into the chronic phase . An example of T 2 * mapping in a porcine model of chronic myocardial infarction is shown in Figure (see the Materials and MRI methods section).…”