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

Abstract

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 T2‐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 T2‐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 T2‐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 T2 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 T2 was detected between the aged mild‐fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T2 relaxation time was derived (R2 = 0.98): T2 (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T2‐map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T2‐mapping MRI is a promising noninvasive contrast agent‐free quantitative technique to characterize myocardial fibrosis.

Quantification of Endometrial Fibrosis Using Noninvasive MRI T2 Mapping: Initial Findings

“…A previous study has shown that tissues with greater fibrillar macromolecules tend to have shorter T2 values 22 . Lee et al found that T2 was significantly lower for fibrotic myocardium than normal myocardium, and that myocardial T2 negatively correlated with interstitial fibrosis 20 . This is consistent with our findings.…”

“…Simple anatomical parameters may only reflect the morphological changes of the endometrium and indirectly evaluate endometrial fibrosis. Several studies have shown that T2 mapping, as a quantitative and functional MRI technique, has shown the superior capability to anatomical parameters in evaluating microstructural changes such as tissues fibrosis 20,33,34 . In addition, the multivariable model combining endometrial T2 and anatomical parameters achieved excellent performance in both distinguishing MMEF from normal endometrium and SEF from normal endometrium.…”

“…Quantitative T2 relaxation time (spin–spin relaxation time), the time constant representing the decay of transverse magnetization, is obtained by a T2 mapping MRI sequence, and can reflect water accumulation and blood volume within tissues 18,19 . T2 mapping has been successfully applied to evaluate myocardial fibrosis and liver fibrosis 20,21 . Fibrotic endometrium has decreased endometrial epithelium, glands, stromal cells and capillary plexus, and increased fibrosis, 10 which can theoretically result in a decreased T2 value compared with normal endometrium 22 .…”

Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging

“…Remarkably, levels of expression of CXCL8 and SERPINE-1 were 4-fold higher in SenCMs vs iCMs. Finally since aged hearts develop significant cardiac hypertrophy 49 , we assessed whether this also occurs in our model. The expression of atrial natriuretic peptides (NPPA) and brain/B-type natriuretic peptides (NPPB), known to be predominantly expressed by the post-natal heart in response to stress-associated hypertrophy 50 , were both significantly upregulated in SenCMs as compared to iCMs (Figure 3 B).…”

Biomarkers of aging

“…Cardiac magnetic resonance (CMR) is a specialized application of MRI which produces high-quality images of cardiovascular system to assess cardiac function and structure. The T2 relaxation time of a quantitative MRI-based T2-mapping decreases significantly in aged hearts (Lee et al, 2022b). As LV compliance reduces with aging, the early radial displacement, radial velocity, and circumferential strain rate decrease, while the late circumferential strain rate increases (Lin et al, 2021).…”