In this study, we presented reference values for native T1 relaxation time and ECV according to LV segments in asymptomatic subjects using a 1.5 T MR system. We found segmental variation in the myocardial tissue composition using CMR T1 mapping in asymptomatic subjects. Females showed higher preT1 and ECV than males. The HTN-DM group showed a significantly higher ECV than the control and HTN groups.
Myocardial fibrosis is commonly associated with cardiac hypertrophy and failure and is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness in animal models . Although endocardial biopsy is the most specific procedure for measuring myocardial fibrosis, it is invasive, and its sensitivity is low due to sampling errors . CMR T1 mapping may serve as a noninvasive biopsy and collagen volume fraction (CVF) was associated with preT1 and ECV in an animal model of myocardial fibrosis [22, 23].
In a pooled summary of 954 healthy subjects from the literature, 3T showed longer T1 than 1.5T with MOLLI variant sequences by approximately 100-200 ms. ECV of the healthy subjects was consistent among the studies (25-27%), irrespective of subject factors, sequences, vendors, and contrast types . In a recent study, normal myocardial T1 reference ranges were reported as follows; at 3-T: 1129-1309 ms and at 1.5-T: 933-1020 ms (males) and 965-1054 ms (females), which tend to be similar to our findings .
Our finding included segmental variations in T1 values and ECV, especially between septal and lateral segments. Motion during the T1 map acquisition may induce a poor T1 model fit and falsely deviated T1 values and ECV, because T1 maps are generated from a sequential series of images . Lateral wall is more vulnerable to motion artifacts which may be a potential cause of the lower preT1 and ECV and the higher postT1 in the lateral segments [10, 26, 27]. Considering low reproducibility of apical T1 values, it may be reasonable to measure T1 values in basal to middle septal walls .
Sex hormones may influence myocardial structure and function [28, 29]. Especially, a previous study demonstrated that estradiol attenuates myocardial hypertrophy . Our observations of higher preT1 and ECV of females than those of males also suggest that sex hormones affect myocardial histology.
There is inconsistency in association of age with T1 values and ECV in the published studies [10, 26, 31–34]. Rauhalamm et al. (28) and Liu et al. (26) demonstrated a linear correlation between age and T1 values and ECV. According to Rosmini et al., native myocardial T1 decreased slightly with age, while ECV did not change with age (29). In our study, aging was not a significant factor affecting T1 values and ECV, which is consistent with a previous study by Dabir et al. (25).
Our results showed that there was no significant difference in ECV between the HTN and control groups. According to previous reports, T1 mapping revealed increased diffuse myocardial fibrosis in well-controlled hypertensive patients, but the increase was small and only occurred with LV hypertrophy (LVH) . Our findings are consistent with the literature, since LVH was contained in the exclusion criteria of our study. Patients with HTN LVH had higher ECV and longer native T1 than HTN non-LVH and control subjects [6, 35]. According to Venkatesh et al., in a study of 1,813 subjects who underwent CMR, HTN-induced remodeling was related to enhanced replacement and diffuse fibrosis . In an animal study, the ECV and native T1 value of the myocardium in 18 hypertensive swine increased over three months, even though no LGE was found at any of the imaging times .
According to Levelt et al., there were no significant differences in native myocardial T1 values and ECV between the patients with DM and the control subjects, indicating the absence of fibrosis in a similar context as our study . Furthermore, our study showed HTN-DM group showed significantly high ECV than the control and HTN groups, which provides a clue about a synergetic effect on ventricular fibrosis of DM and HTN. DM appears to enhance fatty acid metabolism, decrease glucose oxidation, and change intracellular signaling, leading to cardiac structure and function alterations, based on prior research and our study [38–40]. Ventricular fibrosis is a common structural and histological hallmark of DM, primarily owing to the deposition of collagen and advanced glycation end-products resulting from altered intracellular signaling and metabolic disturbances . In a study of 135 patients with DM, ECV was significantly different from that of control subjects, while native T1 was not significantly different . ECV values correlated with HbA1c levels in DM . The group with HbA1c ≥7.0 had a significantly higher ECV value than the control subjects and the lower HbA1c group (HbA1c <7.0). There was no statistically significant difference in the native T1 value and postT1 value among the three groups . The lack of significance between the control and DM groups in ECV can be explained by Hb A1c below 7.2 in our research population.
In our study, in the control group, GFR significantly correlated not with preT1 linearly but with postT1 proportionally and ECV inversely. This interesting finding suggests that postT1 may be associated with the degrees of renal clearance of contrast agent. Increased renal clearance of contrast agent could facilitate washout of contrast agent in myocardium and then increase myocardial postT1 values [44, 45]. According to Edward et al., patients with chronic kidney disease had increased native T1 values and ECV compared with the control and hypertensive subjects .
The limitations of this study include the retrospective cross-sectional study design, the relatively small number of subjects with DM (n = 25), DM and HTN (n = 29), and female subjects (n = 23), and a relatively narrow range of age distribution concentrated in 50s resulting from the consecutive data collection. Low ICCs for measurement of apical segments are ascribed to small ROIs and image inhomogeneity associated with motion.
In conclusion, there were significant differences between the T1 values and ECV of the septal and lateral walls at the mid-ventricular and basal levels in asymptomatic subjects. Females had significantly higher preT1 and ECV values than males. ECV is significantly affected by cardiovascular risk factors such as HTN, DM, and decreased renal function, even before cardiovascular symptoms develop.