Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T-2-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T-2-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T-2-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T-2 relaxation times (25.3 +/- 0.6 in aged vs. 29.9 +/- 0.7 ms in young mice, p = 0.002; and 24.3 +/- 1.7 in PO vs. 28.7 +/- 0.7 ms in shams, p = 0.05). However, no significant difference in T-2 was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T-2 relaxation time was derived (R-2 = 0.98): T-2 (ms) = 30.45 - 1.05 x FP. Thus, these results demonstrate a statistical agreement between T-2-map-quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T-2-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.