Kang Wang1, William Haufe1, Nikolaus Szeverenyi1, Alexandra Schlein 1, Tanya Wolfson 2, Michael S. Middleton1, Jeffrey Schwimmer3, Kimberley Newton3, Cynthia Behling3, Janis Durelle3, Melissa Paiz3, Jorge Angeles3, Len Lazaro4, Diana De La Pena4, Carolyn Hernandez4, Rohit Loomba 4, Meng Yin5, Kevin Glaser5, Richard Ehman5, and Claude Sirlin1
1Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, CA, United States, 2Computational and Applied Statistics Laboratory, University of California, San Diego, San Diego, CA, United States, 3Department of Pediatric, University of California, San Diego, San Diego, CA, United States, 4NAFLD Translational Research Unit, Division of Gastroenterology, University of California, San Diego, San Diego, CA, United States, 5Departments of Radiology, Mayo Clinic, Rochester, MN, United States
Synopsis
To
investigate the effect of different echo times (TE) in 2D MR elastography (2D
MRE) to estimate hepatic stiffness, two 2D MRE scans were acquired in 50
patients using a 3T GE scanner, one with a default TE value of 20.1 ms
(default-TE), and with a nearest in-phase TE value of 20.6 ms (IP-TE).
Wave-image quality of each scan was measured quantitatively by ROI size. We
demonstrated that 2D MRE with an in-phase TE provides slightly higher
wave-image quality in patients with high PDFF, and potentially may be
advantageous for fibrosis assessment in NAFLD.Purpose
Hepatic stiffness estimated using 2D MRE has become the
leading biomarker for liver fibrosis and thus has been advocated in assessment
of NAFLD
1, 2. However, the standard 2D MRE imaging sequence used in most
commercial implementations is a gradient-recalled-echo (GRE) sequence which may
have a default echo time (TE) when fat and water signals are not in-phase
3. Using TE times that
are not in-phase can potential result in
signal cancelation in patients with severe steatosis, thereby reducing signal-to-noise
ratio (SNR) of computed wave images. Because tissue stiffness estimation accuracy
depends on wave-image quality, choice of TE may affect hepatic stiffness estimation
in patients with NAFLD. The purpose of our study was to compare in NAFLD
patients hepatic stiffness estimation and wave-image quality of MRE with a
default TE and MRE with TE at the nearest in-phase value.
Methods
After obtaining informed
consent/assent, adult and pediatric subjects with known or suspected NAFLD were
prospectively enrolled. Hepatic proton-density fat fraction (PDFF), a biomarker
for hepatic steatosis, was estimated with an advanced T1-independent, T2*-corrected
multi-peak, fat-spectrum-modeled sequence
4. Two 2D MRE scans were performed on a 3T GE
HDxt MRI scanner with a motion-sensitized GRE sequence, one with a default TE value
of 20.1 ms (default-TE), and with a nearest in-phase TE value of 20.6 ms (IP-TE)
3. To evaluate wave-image quality objectively, a confidence map was generated
depicting wave image goodness of fit to a smooth polynomial, pixel-by-pixel
(i.e., R2)
5. Confidence
map values ranged from 0 to 1, with '1' indicating high quality wave data
5. Using a custom
software package (MRE/Quant, Mayo Clinic), an image analyst drew regions of
interest (ROIs) on anatomic magnitude images to include only liver parenchyma,
co-localized to the elastogram for both IP-TE and default-TE, and final ROIs
were created separately for the two MRE methods by excluding values not meeting
a confidence-map R2 threshold of 0.95. Mean hepatic stiffness within
final ROIs, and final ROI sizes were recorded. Final ROI size represents the area
of the liver producing good wave data where reliable hepatic stiffness measurements
can be obtained, and was used as a quantitative measure of wave-image quality. Mean hepatic stiffness
and ROI size between default-TE and IP-TE were compared using the pairwise Wilcoxon
rank-sum test. The comparison was repeated for a subgroup of subjects with hepatic
PDFF greater than 20%, for which water and fat signal cancelation is expected
to be substantial. In addition, the relationship between PDFF and the
difference in ROI size between IP-TE and default-TE was examined using Pearson's
correlation.
Results
Fifty subjects
(mean age 46 yrs, range 9-78 yrs, mean BMI 29 kg/m
2, range 20-51
kg/m
2) were enrolled between 5/2015 and 9/2015 with hepatic PDFF
ranging from 0.23% to 35%, and mean hepatic stiffness ranging from 1.61 kPa to
9.64 kPa. Overall, mean hepatic stiffness and ROI size were not different
between IP-TE and default-TE (p=0.16 for hepatic stiffness, p=0.52 for ROI size). For the subgroup with hepatic PDFF
greater than 20% (n = 12), ROI size was larger when using IP-TE compared to default-TE
(5,380 voxels vs. 4,505 voxels; p = 0.0049), but mean computed hepatic
stiffness was not different (2.36 kPa vs. 2.40 kPa; p = 0.1294). In
addition, hepatic PDFF correlated positively with difference in ROI size
between IP-TE and default-TE (r = 0.67, p < 0.0001).
Discussion and Conclusion
Hepatic
stiffness estimation for the two MRE scans with different TEs are in excellent
agreement, indicating that standard 2D MRE acquisition works well over a wide
range of hepatic PDFF, and thus is useful in the assessment of NAFLD. For
patients with moderate to severe steatosis, increasing to an IP-TE increased
the area where accurate stiffness measurements can be obtained by roughly 16%. The
positive correlation between PDFF and difference in ROI size suggests that this
improvement in coverage of the liver is larger for higher PDFF. In summary, 2D MRE
with an in-phase TE provides slightly higher wave-image quality in patients with high PDFF, and potentially may
be advantageous for fibrosis assessment in NAFLD.
Acknowledgements
The research is supported by the following research grants: R01 DK106419, R56 DK090350
References
1. R. Muthupillai, D. Lomas, P. Rossman, J.
Greenleaf, A. Manduca, and R. Ehman, “Magnetic resonance elastography by direct
visualization of propagating acoustic strain waves,” Science, vol. 269,
no. 5232, pp. 1854–1857, Sep. 1995.
2. R. Loomba, T. Wolfson, B. Ang, J. Booker,
and C. Behling, “Magnetic resonance elastography predicts advanced fibrosis in
patients with nonalcoholic fatty liver disease: A prospective study - Loomba -
Hepatology - Wiley Online Library,” …, 2014.
3. M. Yin, J. A. Talwalkar, K. J. Glaser, A.
Manduca, R. C. Grimm, P. J. Rossman, J. L. Fidler, and R. L. Ehman, “Assessment
of Hepatic Fibrosis With Magnetic Resonance Elastography,” Clinical
Gastroenterology and Hepatology, vol. 5, no. 10, pp. 1207–1213.e2, Oct.
2007.
4. S. B. Reeder, I. Cruite, G. Hamilton, and
C. B. Sirlin, “Quantitative assessment of liver fat with magnetic resonance
imaging and spectroscopy.,” J Magn Reson Imaging, vol. 34, no. 4, pp.
729–749, Oct. 2011.
5. B. Dzyubak, K. Glaser, M. Yin, J.
Talwalkar, J. Chen, A. Manduca, and R. L. Ehman, “Automated liver stiffness
measurements with magnetic resonance elastography.,” J Magn Reson Imaging,
vol. 38, no. 2, pp. 371–379, Aug. 2013.