Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver

Abstract

As the burden of liver disease reaches epidemic levels, there is a high unmet medical need to develop robust, accurate and reproducible non-invasive methods to quantify liver tissue characteristics for use in clinical development and ultimately in clinical practice. This prospective cross-sectional study systematically examines the repeatability and reproducibility of iron-corrected T1 (cT1), T2*, and hepatic proton density fat fraction (PDFF) quantification with multiparametric MRI across different field strengths, scanner manufacturers and models. 61 adult participants with mixed liver disease aetiology and those without any history of liver disease underwent multiparametric MRI on combinations of 5 scanner models from two manufacturers (Siemens and Philips) at different field strengths (1.5T and 3T). We report high repeatability and reproducibility across different field strengths, manufacturers, and scanner models in standardized cT1 (repeatability CoV 1.7%, bias -7.5ms, 95% LoA of -53.6 ms to 38.5 ms; reproducibility CoV 3.3%, bias 6.5 ms, 95% LoA of -76.3 to 89.2 ms) and T2* (repeatability CoV 5.5%, bias -0.18 ms, 95% LoA -5.41 to 5.05 ms; reproducibility CoV 6.6%, bias -1.7 ms, 95% LoA -6.61 to 3.15 ms) in human measurements. PDFF repeatability (0.8%) and reproducibility (0.75%) coefficients showed high precision of this metric. Similar precision was observed in phantom measurements. Inspection of the ICC model indicated that most of the variance in cT1 could be accounted for by study participants (ICC = 0.91), with minimal contribution from technical differences. We demonstrate that multiparametric MRI is a non-invasive, repeatable and reproducible method for quantifying liver tissue characteristics across manufacturers (Philips and Siemens) and field strengths (1.5T and 3T).

Clinical assessment of hepatic steatosis and iron content using three-dimensional (3D) multi-echo chemical shift encoded magnetic resonance imaging (MRI): correlation with histopathology

“…The PDFF measurements in our study showed excellent correlation with histological steatosis grades, which is consistent with previous investigations but extends these findings to a larger patient cohort ( 24 ). The exceptional diagnostic performance across all steatosis grades, with AUC values ranging from 0.932 to 0.992, demonstrates the robust capability of 3D multi-echo Dixon sequences for accurate fat quantification.…”

Clinical assessment of hepatic steatosis and iron content using three-dimensional (3D) multi-echo chemical shift encoded magnetic resonance imaging (MRI): correlation with histopathology

“…The PDFF measurements in our study showed excellent correlation with histological steatosis grades, which is consistent with previous investigations but extends these findings to a larger patient cohort ( 24 ). The exceptional diagnostic performance across all steatosis grades, with AUC values ranging from 0.932 to 0.992, demonstrates the robust capability of 3D multi-echo Dixon sequences for accurate fat quantification.…”

Bias, Repeatability and Reproducibility of Liver T1 Mapping With Variable Flip Angles

“…The RE is ±10% if all scans are performed on a single scanner and ±27% if scanners from different vendors and field strengths are used. Bias estimate, repeatability, and reproducibility of MOLLI T 1 measurements are consistent with those reported in the literature using IR/LL T 1 mapping methods in the liver 29,32 . More detailed performance metrics for each sequence, field strength, and vendor are provided in Table S2.…”

“…, and reproducibility of MOLLI T 1 measurements are consistent with those reported in the literature using IR/LL T 1 mapping methods in the liver 29,32. More detailed performance metrics for each sequence, field strength, and vendor are provided in TableS2.…”

Optimized acquisition for simultaneous intravoxel incoherent motion and R2 quantification in the liver

“…Importantly, the magnitude of the relative mean differences was greater than or similar to the test–retest repeatability (CV ≤ 4.58%, 8.94%, and 18.8%, respectively) and intersubject variability (relative SDs = SD/mean ≤ 7.03%, 9.87%, and 21.3%) observed in this work for the right lobe using the b ‐ M 1 ‐ TE ‐optimized IVIM data acquisition, except for estimates of f c1 (CV = 27.5% and relative SD = 38.4%). Further, the test–retest repeatability of the IVIM parameters observed in this work were comparable to that reported for other MR biomarkers commonly used to evaluate diffuse liver disease, such as MR elastography–derived liver stiffness (CV = 4.95%–12.5%) 47–49 and MRI‐derived proton density fat fraction (CV = 5.48%–15.7%) 50–52 . This suggests that IVIM parameters derived using b ‐ M 1 ‐ TE ‐optimized IVIM data acquisitions may provide clinical diagnostic value and enable treatment monitoring.…”

Clinical assessment of hepatic steatosis and iron content using three-dimensional (3D) multi-echo chemical shift encoded magnetic resonance imaging (MRI): correlation with histopathology

“…The PDFF measurements in our study showed excellent correlation with histological steatosis grades, which is consistent with previous investigations but extends these findings to a larger patient cohort ( 24 ). The exceptional diagnostic performance across all steatosis grades, with AUC values ranging from 0.932 to 0.992, demonstrates the robust capability of 3D multi-echo Dixon sequences for accurate fat quantification.…”

Bias, Repeatability and Reproducibility of Liver T1 Mapping With Variable Flip Angles

“…The RE is ±10% if all scans are performed on a single scanner and ±27% if scanners from different vendors and field strengths are used. Bias estimate, repeatability, and reproducibility of MOLLI T 1 measurements are consistent with those reported in the literature using IR/LL T 1 mapping methods in the liver 29,32 . More detailed performance metrics for each sequence, field strength, and vendor are provided in Table S2.…”

“…, and reproducibility of MOLLI T 1 measurements are consistent with those reported in the literature using IR/LL T 1 mapping methods in the liver 29,32. More detailed performance metrics for each sequence, field strength, and vendor are provided in TableS2.…”

Optimized acquisition for simultaneous intravoxel incoherent motion and R2 quantification in the liver

“…Importantly, the magnitude of the relative mean differences was greater than or similar to the test–retest repeatability (CV ≤ 4.58%, 8.94%, and 18.8%, respectively) and intersubject variability (relative SDs = SD/mean ≤ 7.03%, 9.87%, and 21.3%) observed in this work for the right lobe using the b ‐ M 1 ‐ TE ‐optimized IVIM data acquisition, except for estimates of f c1 (CV = 27.5% and relative SD = 38.4%). Further, the test–retest repeatability of the IVIM parameters observed in this work were comparable to that reported for other MR biomarkers commonly used to evaluate diffuse liver disease, such as MR elastography–derived liver stiffness (CV = 4.95%–12.5%) 47–49 and MRI‐derived proton density fat fraction (CV = 5.48%–15.7%) 50–52 . This suggests that IVIM parameters derived using b ‐ M 1 ‐ TE ‐optimized IVIM data acquisitions may provide clinical diagnostic value and enable treatment monitoring.…”

Clinical assessment of hepatic steatosis and iron content using three-dimensional (3D) multi-echo chemical shift encoded magnetic resonance imaging (MRI): correlation with histopathology

“…The PDFF measurements in our study showed excellent correlation with histological steatosis grades, which is consistent with previous investigations but extends these findings to a larger patient cohort ( 24 ). The exceptional diagnostic performance across all steatosis grades, with AUC values ranging from 0.932 to 0.992, demonstrates the robust capability of 3D multi-echo Dixon sequences for accurate fat quantification.…”

Bias, Repeatability and Reproducibility of Liver T1 Mapping With Variable Flip Angles

“…The RE is ±10% if all scans are performed on a single scanner and ±27% if scanners from different vendors and field strengths are used. Bias estimate, repeatability, and reproducibility of MOLLI T 1 measurements are consistent with those reported in the literature using IR/LL T 1 mapping methods in the liver 29,32 . More detailed performance metrics for each sequence, field strength, and vendor are provided in Table S2.…”

“…, and reproducibility of MOLLI T 1 measurements are consistent with those reported in the literature using IR/LL T 1 mapping methods in the liver 29,32. More detailed performance metrics for each sequence, field strength, and vendor are provided in TableS2.…”

Optimized acquisition for simultaneous intravoxel incoherent motion and R2 quantification in the liver

“…Importantly, the magnitude of the relative mean differences was greater than or similar to the test–retest repeatability (CV ≤ 4.58%, 8.94%, and 18.8%, respectively) and intersubject variability (relative SDs = SD/mean ≤ 7.03%, 9.87%, and 21.3%) observed in this work for the right lobe using the b ‐ M 1 ‐ TE ‐optimized IVIM data acquisition, except for estimates of f c1 (CV = 27.5% and relative SD = 38.4%). Further, the test–retest repeatability of the IVIM parameters observed in this work were comparable to that reported for other MR biomarkers commonly used to evaluate diffuse liver disease, such as MR elastography–derived liver stiffness (CV = 4.95%–12.5%) 47–49 and MRI‐derived proton density fat fraction (CV = 5.48%–15.7%) 50–52 . This suggests that IVIM parameters derived using b ‐ M 1 ‐ TE ‐optimized IVIM data acquisitions may provide clinical diagnostic value and enable treatment monitoring.…”