This retrospective study was approved by the institutional review board of Seoul National University Hospital (IRB no. 1902-053-1008), and the requirement for informed consent was waived. All methods were performed in accordance with the relevant guidelines and regulations.
To evaluate the accuracy of T1 values obtained with the MOLLI sequence, we prepared an acrylic box of twelve cylindrical tubes (3 × 3 × 6 cm) with different concentrations of gadoterate meglumine (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, and 3 mmol/L, respectively) (Fig. 5). We scanned the phantom with four different methods of T1 mapping, which included 2D SE-IR, VFA, VFA with B1 correction, and MOLLI sequences. To evaluate the reproducibility of T1 values obtained by the MOLLI sequence, we scanned these phantom tubes three times with the MOLLI sequence.
A series of IR sequences was obtained using the following parameters: repetition time (TR) = 2550 ms; echo time (TE) = 10 ms; Flip angle (FA) = 90°; field of view (FOV) = 260 × 260 mm2; matrix = 256 × 256 pixels; slice thickness = 8.0 mm; inversion time (TI) = 50, 400, 1100, and 2500 ms; total acquisition time = 43 min and 48 s.
For the VFA method, we used three different flip angles to obtain the T1 map with VFA sequence. Three dimensional (3D) volumetric interpolated breath-hold examination (VIBE) was used and the parameters used were as follows: TR = 5.2 ms; TE = 1.76 ms; flip angle (FA) = 2°, 5°, 15°; FOV = 195 × 260 mm2; matrix = 160 × 320 pixels; slice thickness = 4.0 mm; generalized auto-calibrating partial parallel acquisition (GRAPPA) acceleration factor = 2; total acquisition time = 15 s.
For the VFA with B1 correction method, the dual flip angle 3D-VIBE sequence was used. The B1 map was obtained before the acquisition of T1 mapping to correct B1 inhomogeneity. The following parameters were used: TR = 15 ms; TE = 1.7 ms; flip angle (FA) = 5°, 26°; FOV = 260 × 260 mm2; matrix = 384 × 384 pixels; slice thickness = 3.0 mm; GRAPPA acceleration factor = 2; acquisition time = 67 s. B1 map sequence based on the spin-echo type, with a slice selective excitation and two refocusing pulses, which generates a spin-echo and a stimulated-echo was used to correct B1 inhomogeneity. The detailed imaging parameters of the B1 map sequence and calculation of T1 values with corrected B1 are provided in Supplementary Information.
The MOLLI sequence consisted of three inversion recovery-prepared look-locker pulses, and the imaging parameters used were as follows: 2D- single-shot balanced steady-state free-precession (bSSFP); TR/TE = 2.32/1.03 ms; flip angle = 35°; number of excitations = 1.0; field of view (FOV) = 349 × 349 mm2; matrix = 192 × 134 pixels; minimum inversion time (TI) = 100 ms; TI increment between inversions = 80 ms; slice thickness = 8 mm; number of inversions = 3; number of acquisitions after an inversion pulse = 3, 3, 5; number of recoveries after each inversion pulse = 4, 4, 0; acquisition time = 12 s. A fully automated non-rigid motion correction was applied to register the individual images (Fig. 6). The cardiac cycle synchronization was performed with pulse oximetry, obtained through a sensor placed on patient`s index finger.
After this, inline fitting was performed using a mono-exponential, three-parameter fit, and T1 maps were automatically calculated using work-in-progress software provided by the vendor (Siemens Healthcare, Erlangen, Germany).
All MR images were obtained at a 1.5 unit (Avanto, Siemens Healthcare, Erlangen, Germany) using a 12-channel head coil and 6-channel phased array body coil. The gadoterate meglumine phantom was scanned under a constant room temperature of 20–21 ℃.
T1 mapping with MOLLI sequence in patients
We obtained liver MRI including MOLLI sequences in combination with cardiac MRI in patient who had a history of congenital heart disease. Additional liver MRI was performed during cardiac MRI in patients who had liver function abnormality with suspicion of congestive hepatopathy. We obtained MOLLI sequences twice (free breathing and breath-hold techniques) in 22 patients who could hold their breath for 20 s. We excluded 2 patients who had focal hepatic masess in liver MRI.
MR imaging acquisition for patients
The MOLLI sequence were obtained without contrast enhancement. One axial slice was chosen at the levels showing the largest area of the liver parenchyma among the baseline, axial, T1-weighted images. The imaging parameters were the same as those used for the phantom study. T1 maps were acquired twice in each patient, one with free breathing and the other with breath-hold technique.
The measurements of T1 relaxation times were achieved by the manual drawing of the regions of interest (ROIs) on the automatically generated T1 maps. In the phantom study, a radiologist (Y. J. C.) with eight years of clinical experience measured T1 values three times in each cylinder on axial T1 maps by drawing approximately 100 mm2-sized circular ROIs in the center of each cylinder. The mean T1 values of each sequence were used for the analysis. The reference standard determination was based on axial, single-section imaging of the phantom midpoint with SE-IR sequence.
In the human study, the measurement of the hepatic T1 relaxation time was performed by two independent radiologists, (Y. J. C. and S. H. L, 8 years of experience) who performed manual drawings of freehand ROIs on the T1 maps with the exclusion of identifiable vascular structures, including hepatic and portal veins (Fig. 7). As obtained in the phantom study, the mean T1 relaxation times were also calculated.
To evaluate the correlation between reference T1 relaxation times obtained by the SE-IR method and the concentration of Gadoterate meglumine, we employed the Pearson correlation analysis; which was also used to identify the correlation between the standard SE-IR methods and the three different methods. We calculated the intraclass correlation coefficient (ICC) and constructed a Bland–Altman plot to evaluate the absolute agreement among the T1 relaxation times of the four different techniques used in the phantom study. The reliability and reproducibility of the T1 MOLLI sequence were evaluated by using the within-subject coefficient of variance (CV) and ICC.
The mean hepatic T1 relaxation times were compared between the free breathing and breath-hold techniques by using paired t-test and Pearson correlation analysis. For evaluating the absolute agreement of T1 values between free breathing and breath-hold MOLLI techniques, we calculated the two-way ICC based on a single-rating, absolute-agreement, and 2-way random effects model. A Bland–Altman plot was constructed, and a 95% limit of agreement was calculated.
A P-value of less than 0.05 was determined as statistically significant. All statistical analyses were performed using commercially available software (MedCalc, Version 12, MedCalc Software, Mariakerke, Belgium; IBM SPSS Statistics, Version 23.0, SPSS Inc., Armonk, NY, USA).
This retrospective study was approved by the institutional review board, which waived the need for patient informed consent.