Assessment of Spin-Echo and Gradient-Echo Liver MRE in Healthy Children and Children with Suspected Fibrosis at 3 T
Tess Armstrong1, Sarai G. Santos2, Karrie V. Ly2, Ely Felker1, Shahnaz Ghahremani1, Xinran Zhong1,3, Robert S. Venick2, Joanna Yeh2, Grace Hyun J. Kim1, Kyunghyun Sung1, Kara L. Calkins2, and Holden H. Wu1

1Radiological Sciences, University of California Los Angeles, Los Angeles, CA, United States, 2Pediatrics, University of California Los Angeles, Los Angeles, CA, United States, 3Physics and Biology in Medicine IDP, University of California Los Angeles, Los Angeles, CA, United States


Magnetic resonance elastography (MRE) accurately measures liver stiffness and correlates with liver histopathology. However, conventional gradient-echo (GRE) MRE sequences require multiple breath-holds. Spin-echo echo-planar-imaging (SE-EPI) MRE only requires a single breath-hold. In this study we compared 2D SE-EPI and 2D rapid-GRE MRE sequences at 3T in healthy children and children with suspected fibrosis. Both SE-EPI and rapid-GRE had good repeatability, reproducibility, inter-reader agreement, and quantitative agreement in liver stiffness. SE-EPI provided larger measurable liver ROI sizes than rapid-GRE. SE-EPI may be desirable for measuring fibrosis in children with limited or inconsistent breath-hold ability and reduce scan times.


The gold standard for diagnosing and staging liver fibrosis is biopsy, which is invasive and limited by sampling bias1,2. Magnetic resonance elastography (MRE) non-invasively quantifies liver stiffness (in kPa), a biomarker for liver fibrosis3–5, and correlates with histopathology3–7. MRE acquisitions typically employ gradient-echo (GRE) or spin-echo echo-planar-imaging (SE-EPI) sequences7–10. Conventional GRE sequences used in clinical practice9 require multiple breath-hold acquisitions to cover multiple slices (15-22s per slice)11. On the other hand, SE-EPI sequences use a single breath-hold of approximately 10s for multiple slices7–10. Recently, a rapid-GRE sequence has been developed to reduce the breath-hold time to 10s per slice and is consistent with conventional GRE measurements in adults11. Children may have more difficulty performing multiple breath-holds and maintaining consistent breath-holds, which may hinder the image quality and limit the area in the liver with sufficient numerical confidence for measuring stiffness3. Therefore, SE-EPI MRE may be a desirable technique for evaluating liver stiffness in children. In this work, we compared 2D rapid-GRE and 2D SE-EPI MRE in healthy children and children with suspected fibrosis at 3T.


MRE Acquisition and Reconstruction: 6 healthy children and 10 children with suspected fibrosis (Table 1) were enrolled in this IRB-approved study. 2D rapid-GRE11 and 2D SE-EPI12 sequences were acquired at 3T (Prisma, Siemens) (Table 2). Each MRE sequence was scanned twice (back-to-back) in the same session to assess repeatability. Subjects were removed from the table, repositioned, and MRE was repeated during another scan session to assess reproducibility. Images and stiffness maps were calculated by scanner software.

Analysis: Liver stiffness (kPa) was measured by two experienced radiologists independently. Differences in liver stiffness between radiologists and sequences were assessed using Pearson’s correlation coefficient (r) and intra-class correlation coefficient (ICC), and Bland-Altman analysis to determine the mean difference (MD) and limits of agreement (LoA). Repeatability and reproducibility were assessed by determining the within-technique mean difference (MDwithin), within-technique standard deviation (SDwithin), and coefficient of repeatability/reproducibility (CR)13. Significant differences between sequences, readers, and repeated/reproduced measurements were assessed using a three-way ANOVA. Liver ROI sizes with sufficient numerical confidence were calculated8 and differences were assessed using a paired t-test after normality testing. P<0.05 was considered significant.


Median(±interquartile range, IQR) liver stiffness in healthy subjects was 2.02(±0.29) kPa and 2.30(±0.71) kPa in subjects with suspected fibrosis. The liver stiffness measurements in healthy subjects were consistent with stage 0 fibrosis. Of the subjects with suspected fibrosis, 1 subject had stage 2 fibrosis and 1 subject had stage 4 fibrosis according to published cutoffs14. Representative rapid-GRE and SE-EPI images from a healthy child and child with liver disease are shown in Figure 1. Linear correlation and Bland-Altman results comparing sequences (Fig. 2a-b) and radiologist measurements (Fig. 2c-d) showed r>0.82 (P<0.001) and ICC>0.82 (P<0.001) with MD<0.1kPa. Repeatability results are reported in Table 3. CRs were smaller for repeated than reproduced scans, rapid-GRE than SE-EPI, and for radiologist 1 compared to radiologist 2, but these differences were not significant. Median±IQR measureable liver ROI size was significantly greater for SE-EPI than rapid-GRE (17,824mm2±2,886mm2 versus 13,259mm2±7,159mm2, P=0.01).


Previous research compared conventional GRE or rapid-fractional-GRE to SE-EPI sequences and were performed at 1.5T in children or at 1.5T and 3T in adults8,9,15. We investigated rapid-GRE and SE-EPI sequences in children at 3T, which bolsters current knowledge. The MD between sequences reported in our study were consistent with previous findings8,9,15. Additionally, inter-reader agreement in children at 1.5T9 and differences between sequences in adults at 3T15 were consistent with our results. Both SE-EPI and rapid-GRE demonstrated good repeatability, reproducibility, inter-reader agreement, and quantitative agreement in liver stiffness measurements. However, the entire acquisition time for rapid-GRE was approximately 2 minutes due to multiple breath-holds and instructions, while SE-EPI was 10s for a single breath-hold. Therefore, SE-EPI may be desirable in patients when the scan time is limited or who may have difficulty performing consistent breath-holds. Another advantage for SE-EPI is the larger measurable liver ROI size, which may be due to improved image quality8. Previous work in children at 1.5T also demonstrated larger ROI size for SE-EPI9. Iron overload can reduce measurable liver ROI size using GRE sequences8. In this study, no children had elevated liver iron (normal range: R2*=69.1s-1±21.9s-1 at 3T16). Further work includes studying additional subjects with biopsy findings to compare MRE liver stiffness to histopathology.


SE-EPI and rapid-GRE provided repeatable, reproducible, inter-reader agreement, and agreement in liver stiffness measurements in healthy children and children with suspected liver fibrosis at 3T. Since SE-EPI has a shorter acquisition time and provides a larger measurable liver ROI size compared to rapid-GRE, it may be a desirable technique to measure liver stiffness for the diagnosis and staging of fibrosis in children.


The authors thank the Departments of Pediatrics and Radiological Sciences at UCLA for funding support. The authors thank Dr. Le Zhang, Xinzhou Li, Tammy Floore, Sparsha Govardhan, Glen Nyborg, and Sergio Godinez at UCLA for their help with recruitment and scanning.


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Table 1: Demographic information for healthy children (n = 6) and children with suspected liver fibrosis (n = 10), reported as median ± interquartile range or percentage% (number). NAFLD: non-alcoholic fatty liver diasese; NASH: Non-alcoholic steatohepatitis; N/A: not applicable. *1 subject had NASH.

Table 2: Representative imaging parameters for 2D rapid gradient-echo (GRE) and 2D spin-echo echo-planar imaging (SE-EPI) MR elastography (MRE) sequences acquired at 3T. The MRE transducer wave amplitude was set to 40-60% amplitude depending on the subjects’ body size.

Table 3: Repeatability and reproducibility results. The within-technique mean difference (MDwithin), within-technique standard deviation (SDwithin) and coefficient of repeatability/reproducibility (CR) are reported for pediatric subjects (healthy and suspected fibrosis) for spin-echo echo-planar imaging (SE-EPI) and rapid gradient-echo (rapid-GRE) MR elastography sequences and for two radiologists. All values are in units of kPa. The ANOVA did not find significant differences between repeated scans (P = 0.97) among radiologists (P = 0.59) and sequences (P = 0.55) and between reproduced scans (P = 0.97) among radiologists (P = 0.68) and sequences (P = 0.79).

Figure 1: Representative SE-EPI and rapid-GRE MRE images. The magnitude, wave, and liver stiffness (kPa) with 95% confidence interval (CI) mask images in (a) a healthy pediatric subject and (b) a pediatric subject with liver disease and MRE results consistent with grade 4 fibrosis. The liver contour is shown in white and the liver stiffness in kPa is shown for a representative region of interest in black.

Figure 2: Linear correlation and Bland-Altman results. The (a,c) linear correlation and (b,d) Bland-Altman results between (a-b) 2D spin-echo echo-planar-imaging (SE-EPI) and 2D rapid gradient-echo (rapid-GRE) liver stiffness measurements (kPa) and between (c-d) two experienced radiologists in pediatric subjects at 3 T. The intra-class correlation coefficient (ICC), Pearson’s correlation coefficient (r), mean difference (MD) and limits of agreement (LoA) are shown. In a and c, the solid line indicates the linear regression and the dashed line indicates the line for y = x. In b and d the dashed line indicates y = 0. A P-value (P) < 0.05 was considered significant.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)