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Proton Density Fat Fraction Estimation Accuracy of High-Flip-Angle, Contrast-Enhanced, Magnitude-Based Multi-Gradient-Echo MR Imaging at 3T
Ethan Z Sy1, Cheng William Hong1, Soudabeh Fazeli Dehkordy1, Charlie C Park1, Alexandra Schlein1, Jonathan C Hooker1, Jennifer Cui1, Gavin Hamilton1, and Claude B Sirlin1

1University of California, San Diego, San Diego, CA, United States

Synopsis

Proton density fat fraction (PDFF) is a widely-used magnetic resonance imaging (MRI)-based biomarker for noninvasive quantification of hepatic steatosis. PDFF derived from low-flip-angle magnitude-based multi-gradient-echo MRI (MRI-M) without intravenous contrast has been shown to have high accuracy for estimating fat fraction. However, this MRI-M technique has a relatively low signal-to-noise ratio (SNR), which makes it difficult to visualize anatomical features. In this analysis of ninety-two patients, high-flip-angle contrast-enhanced (with either gadoxetate disodium or gadobutrol) MRI-M imaging had no significant difference in fat-grading accuracy from the standard low-flip-angle pre-contrast PDFF, using MR spectroscopy (MRS)-PDFF as the reference standard.

Introduction

Proton density fat fraction (PDFF) is a method of noninvasive quantification of hepatic steatosis derived from magnitude-based multi-gradient-echo MRI (MRI-M). PDFF estimation utilizing a six-echo multi-frequency model with low-flip-angle (FA) has been proven to have both high diagnostic and grading accuracy2-4. Low FA is used because high-FA tends to overestimate PDFF due to increased T1 weighting1. However, the T1 of fat and water are similar in gadolinium-enhanced acquisitions, thus mitigating this confounder1. Administration of intravenous contrast agents allows the use of high-FA imaging to achieve higher signal-to-noise ratio (SNR)5. We hypothesize that high-flip-angle, contrast-enhanced, magnitude-based multi-gradient-echo MR imaging can provide an accurate estimation of PDFF by combining the opposing effects of contrast and high FA on PDFF estimation while maintaining a high SNR. The primary aim of this study was to compare the PDFF estimation accuracy of post-contrast high-FA MRI-M with the standard pre-contrast low-FA MRI-M, using MR spectroscopy (MRS)-PDFF as the reference standard.

Methods

We performed a retrospective analysis of adults who underwent either gadoxetate- or gadobutrol-enhanced clinical 3T liver MRI from March 2016 to September 2016. MRS was performed pre- and post-contrast to measure MRS-PDFF. Low (10º)-FA MRI-M sequences were acquired before administration of contrast, and high (50º)-FA MRI-M sequences were acquired during the delayed phase. MRI-PDFF was estimated by placing a 1-cm radius region-of-interest (ROI) in each of the nine Couinaud hepatic segments, and three additional ROIs were placed co-localized to the MRS voxel. PDFF values from the 9 hepatic segments were averaged to obtain a composite whole-liver PDFF. Linear regression was performed with the mean co-localized MRI-PDFF as the predictor variable and MRS-PDFF as the response variable for both MRI-M sequences (pre-contrast 10º-FA and post-contrast 50º-FA). Bland-Altman analysis was performed to assess the variation of the bias PDFF estimated between the two MRI-M techniques and its dependence on mean PDFF.

Results

Ninety-eight patients were included in this analysis (46 female, 52 male; mean age of 60.2 ± 14.6 years, range: 19 – 87). Linear regression slopes for both 10º and 50º-FA fit closely with MRS, with R2 of 0.920 (low-FA) and 0.938 (high-FA). The mean bias between post-contrast PDFF and pre-contrast PDFF was -0.449 (limits of agreement: -2.16, +1.27). The correlation coefficient between mean PDFF and the average bias was -0.66 (p < 0.001).

Discussion

Using MRS as the reference standard, we observed that contrast-enhanced (gadoxetate and gadobutrol) high-FA MRI-M sequences have similar fat estimation accuracy compared to low-FA MRI-M across a large PDFF range (0-35%). Bland-Altman analysis pre-contrast low-FA sequence estimates higher PDFF values than post-contrast high-FA sequence on average. The increase in SNR in the post-contrast 50º-FA sequence from the pre-contrast 10º-FA (Figure 4) allows for better distinction between anatomical features. Although further validation is necessary, our findings suggest that PDFF can be accurately estimated using high-FA in patients obtaining intravenous gadoxetate or gadobutrol.

Conclusion

High-FA post-contrast PDFF estimation using magnitude-based MRI displays no significant difference in accuracy from the standard low-FA pre-contrast PDFF relative to MRS, although the high-FA technique tends to estimate lower PDFF values.

Acknowledgements

No acknowledgement found.

References

1. Bydder M, Yokoo T, Hamilton G, et al. Relaxation effects in the quantification of fat using gradient echo imaging. J Magn Reson Imaging. 2008;26.3:347-359.

2. Yokoo T, Shiehmorteza M, Hamilton G, et al. Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T. Radiology. 2011;258(3):749-759.

3. Tang A, Tan J, Sun M, et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology. 2013;267(2):422-431.

4. Reeder SB, Hu HH, Sirlin CB. Proton density fat-fraction: A standardized MR-based biomarker of tissue fat concentration. J Magn Reson Imaging. 2012;36(5):1011-1014.

5. Tajima T, Takao H, Akai H, et al. Relationship between liver function and liver signal intensity in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging. J Comp Assis Tomog. 2011;34(3):362-366.

Figures

Figure 1: Linear regression plot comparing pre-contrast PDFF to pre-contrast MRS. Sequences were acquired prior to administration of contrast. Each data point represents a single unique patient.

Figure 2: Linear regression plot comparing post-contrast PDFF to post-contrast MRS. Sequences were acquired during the delayed. Each data point represents a single unique patient.

Bland-Altman Plot comparing pre-contrast MRI-M PDFF to post-contrast MRI-M PDFF. Markers have been placed to distinguish patients who received intravenous gadoxetate or gadobutrol. A negative correlation exists between mean PDFF and bias.

Source echo (echo time (TE): 5.8 and repetition time (TR): 150) for both MRI-M techniques in a single patient. The noise present in the 10º-FA acquisition interferes with the identification of several anatomical features. The 50º-FA acquisition provides a higher SNR in the case above, which allows for visualization of vasculature and the mass present in segment 8.

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)
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