Myocardial tissue characterization and strain analysis in healthy pregnant women using cardiovascular magnetic resonance native T1 mapping and feature tracking technique

Fourteen healthy pregnant women were prospectively recruited from between June 2015 and August 2016. Eligible subjects were between the age of 20 and 39 years at their last normal menstrual period, carrying a healthy singleton pregnancy. Exclusion criteria included any history of hypertension, diabetes mellitus, smoking, thyroid disease, known cardiac disease, any pregnancy-related complications including preeclampsia, hypertensive disorders of pregnancy, gestational diabetes, and the presence of a pacemaker or general contraindications to CMR. Of the 14 pregnant women, two were subsequently excluded because of hypertensive disorders of pregnancy. All 12 remaining women (33 ± 4 years) had a normal delivery between September 2015 and November 2016. This population was compared with 15 age-matched healthy non-pregnant women (31 ± 3 years). All 12 pregnant women underwent CMR three times, in the 2nd and 3rd trimesters of pregnancy and at 1 month postpartum, with a simultaneous 5.0 mL blood sample drawn to determine concentrations of hemoglobin (Hb) and brain type natriuretic peptide (BNP). Fifteen non-pregnant women also underwent CMR and provided a 5.0 mL blood sample immediately after the CMR examination and served as control women.

CMR studies were performed on a 1.5 T CMR scanner (Achieva 1.5 T, Philips Healthcare, Best, The Netherlands) using a body coil for signal reception. No sedative medications or contrast agents were used, and all participants were imaged in the half left lateral decubitus position to minimize aortocaval compression. The CMR study protocol included cine CMR and native T1 mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Cine MR images were acquired with a retrospective electrocardiographic gating and a segmented steady-state-free precession sequence during brief periods of breath-holding at a shallow expiration in the following planes: LV 2-chamber and 4-chamber views and short-axis planes covering the entire LV and right ventricle (RV) (repetition time [TR] 2.9 ms; echo time [TE] 1.44 ms; flip angle [FA] 55°; field of view [FOV] 350 × 350 mm²; acquisition matrix 176 × 176; reconstruction matrix 256 × 256; slice thickness 10 mm). All cine images were acquired with 20 phases per cardiac cycle. The short-axis plane was defined as the perpendicular plane to the horizontal and vertical long-axis views. Single-slice native T1 mapping was performed using a 17-heartbeat steady-state-free procession MOLLI sequence on the short-axis imaging plane at the level of the mid LV (TR, 2.3 ms; TE, 0.83 ms; FA, 35°; FOV, 300 × 327 mm²; acquisition matrix, 176 × 140; reconstruction matrix, 288 × 288; slice thickness, 10 mm) [25].

CMR image analyses were carried out by an expert observer who had 15 years of CMR experience (M.I.) using CMR analysis software, cvi42 (Circle Cardiovascular Imaging Inc., Calgary, Canada). LV volume and function were analyzed based on the short-axis cine stack (Fig. 1). The endocardial and epicardial borders of the LV wall were manually traced on cine CMR images in end-diastolic and end-systolic phases. LVM was calculated as the volume of the LV myocardium multiplied by the specific gravity of the myocardium (1.05 g/ml) [26]. Mean LV wall thickness was measured in the end-diastolic phase on the short-axis view. The papillary muscles and trabeculations were not included in the myocardial mass calculation. Then, RV volume and function were analyzed based on the short-axis cine stack. LV and RV measurements were indexed to body surface area (BSA). Strain analysis was performed by a feature-tracking algorithm [11]. The endocardial and epicardial borders of LV and RV myocardium were manually traced in the end-diastolic phase of a 4-chamber view cine CMR image. Then, the software automatically propagated the endocardial and epicardial contours and tracked the motion of the in-plane tissue voxels through the entire cardiac cycle. Consequently, peak longitudinal strain values were recorded at global levels for the LV and RV. Native T1 measurement was performed pixel-wise. After correcting for respiratory motion of the images by non-rigid image registration, T1 maps were generated by fitting pixels to the equation s (t) = a-b exp. (−t/T1*), and T1 = (b/a-1) T1*, where a and b are constants, t is time, and s (t) is signal intensity at time t [27]. The resulting pixel-wise native T1 maps were stored in DICOM format, and native T1 values were averaged for all pixels (Fig. 2).

The statistical analyses were performed using SPSS Statistics 20.0 (International Business Machiens, Armonk, New York, USA). Data were normally distributed (Kolmogorov-Smirnov test), and all data are therefore presented as means ± standard deviation (SD). Changes in variables within a group were compared using the paired t-test with the post hoc Tukey-Kramer method. Analysis of variance (ANOVA) was used for comparisons of multiple groups. Pearson’s product-moment correlation coefficient was used to measure linear correlations between two variables. In all analyses, p < 0.05 was taken to indicate significance. However, a significant linear correlation between two variables was defined as that meeting both p < 0.05 and correlation coefficient (r-value) > 0.2 or < − 0.2 [28].

The demographic characteristics of the healthy pregnant women and non-pregnant women are summarized in Table 1. Between pregnant and non-pregnant women were similar in age (33 ± 4 and 31 ± 3 years, p = 0.126), body mass index (BMI) (19.3 ± 0.7 and 20.2 ± 1.5 kg/m², p = 0.067), and BSA (1.50 ± 0.09 and 1.49 ± 0.09 m², p = 0.848). However, the proportion of nulliparous women was significantly different (5 (42%) and 14 (93%) respectively, p < 0.05, Fisher’s exact test).

CMR examination and blood tests were performed at gestational week 25.3 ± 0.6 (26.4 to 24.0) and 33.7 ± 0.7 (34.9 to 33.1) for the 2nd and 3rd trimesters of pregnancy, respectively, and on postpartum day 35 ± 4 (41 to 31).

Hemoglobin concentrations were significantly higher 1 month postpartum than in the 2nd, 3rd trimesters and in non-pregnant women. The BNP concentration was significantly higher in the 2nd trimester than at 1 month postpartum and in non-pregnant women.

The structural and systolic functional parameters of the LV and RV determined by cine CMR, including peak global longitudinal strain (GLS), in the pregnant women and in the non-pregnant women are summarized in Tables 2 and 3, respectively. In pregnant women, LV stroke volume (SV) was not substantially altered during pregnancy compared to 1 month postpartum, but heart rate (HR) was significantly higher in the 2nd trimester than at 1 month postpartum (76 ± 8 vs 64 ± 8 bpm; p < 0.05), resulting in significantly greater cardiac output (CO) and cardiac index (CI) in the 2nd trimester (5.7 ± 1.6 L/min and 3.7 ± 0.9 L/min/m²) than at 1 month postpartum (4.3 ± 1.1 L/min and 2.8 ± 0.7 L/min/m², p < 0.05) and in non-pregnant women (4.3 ± 0.7 L/min and 2.9 ± 0.4 L/min/m², p < 0.05), respectively. As with LV, RV CO (6.2 ± 1.3 mL/min) and CI (4.0 ± 0.7 mL/min/m²) were significantly greater in the 2nd trimester than at 1 month postpartum (4.9 ± 0.9 mL/min, p < 0.05 and 3.2 ± 0.5 mL/min/m², p < 0.05) and in non-pregnant women (4.8 ± 0.6 mL/min, P < 0.05 and 3.2 ± 0.3 mL/min/m², p < 0.05), respectively. LV end-diastolic volume (EDV) was significantly greater in the 3rd trimester (126 ± 22 mL) than in non-pregnant women (108 ± 14 mL, p < 0.05). LVM and LVM index were significantly greater in the 3rd trimester (88.7 ± 11.8 g and 56.5 ± 6.5 g/m²) than at 1 month postpartum (72.0 ± 9.8 g, p < 0.05 and 47.5 ± 6.0 g/m², p < 0.05) and in non-pregnant women (66.3 ± 13.9 g, p < 0.05 and 44.5 ± 8.0 g/m², p < 0.05), respectively (Fig. 3). Mean LV wall thickness was also significantly greater in the 3rd trimester (5.09 ± 0.57 mm) than at 1 month postpartum (4.53 ± 0.50 mm, p < 0.05) and in non-pregnant women (4.57 ± 0.63 g, p < 0.05). Pearson’s linear correlation coefficients were 0.76 (p < 0.001), 0.75 (p < 0.001), and 0.56 (p < 0.001) for LVEDV, LV end-systolic volume (ESV), and LVM, respectively, against actual body weight.

LV GLS showed no significant difference among the 2nd and 3rd trimesters, 1 month postpartum, and in non-pregnant women (− 19.5 ± 1.8, − 19.7% ± 2.2, − 19.0% ± 2.0%, and − 19.3 ± 1.9%, respectively, p = 0.66) (Fig. 4). RV GLS also showed no significant difference among the 2nd and 3rd trimesters, 1 month postpartum, and non-pregnant women (− 28.0 ± 3.1, − 25.6% ± 3.4, − 25.7% ± 3.9%, and − 26.0% ± 5.0%, respectively, p = 0.42) (Fig. 4).

Native myocardial T1 in pregnant women was 1133 ± 55 ms (95%CI 1095.8 to 1169.4 ms), 1138 ± 86 ms (95%CI 1081 to 1194 ms), and 1105 ± 45 ms (95% CI 1075 to 1134 ms) in the 2nd trimester, the 3rd trimester, and at 1 month postpartum, respectively, whereas native myocardial T1 in non-pregnant women was 1129 ± 52 ms (95% CI 1100 to 1159 ms) (Fig. 5). Thus, no significant difference was noted in native myocardial T1 among the 2nd and 3rd trimesters, 1 month postpartum, and non-pregnant women (p = 0.59). Pearson’s linear correlation analysis demonstrated that native myocardial T1 was not correlated with LVM, with r of 0.16 and p = 0.27 (Fig. 6).

In this study, reference values of myocardial T1 relaxation time and GLS were determined in 12 Japanese normal pregnant women. These data are useful to determine if these CMR parameters are abnormal in patients with suspected PPCM. The current results can also serve as an important baseline not only in PPCM patients, but also in other pregnancy-related cardiac diseases, for example, in identifying myocardial edema or inflammation in pregnant patients with acute myocarditis.

There are three limitations in this study. First, there was a small number of participants. The age distribution of the pregnant women is an important issue since it pertains to the age range of 20–35 years and the age range of 35–39 years. In the present study population, the numbers of subjects in the age range of 20–35 years and the age range of 35–39 years were 8 and 4 in pregnant women and 12 and 3 in non-pregnant controls, respectively. However, because of the small sample size, it was not possible to show any significant age-related differences among the group and between groups. Future studies with a larger number of participants are warranted. Second, there was a difference in parity between pregnant women and non-pregnant controls. Third, no CMR findings were compared to the results of cardiac biopsy or heart catheterization as the gold standard technique for tissue characterization or functional assessment of the heart.