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Feasibility of Assessing the Nonlinear Mechanical behaviors of Liver with MR Elastography (MRE)
Ziying Yin1, Bogdan Dzyubak1, Jiahui Li1, Kevin J. Glaser1, Sudhakar Venkatesh1, Armando Manduca1, Richard L Ehman1, and Meng Yin1

1Radiology, Mayo clinic, Rochester, MN, United States

Synopsis

This is a feasibility study for assessing the nonlinear mechanical behaviors of the liver while experiencing different degrees of mechanical preloads. The different loading conditions were induced by 1) diaphragm movement in a view-sharing free-breathing 2D-EPI-MRE acquisition; 2) end-expiration versus end-inspiration states in a breath-held 3D-EPI-MRE acquisition. We observed intriguing stiffness variation synchronized with the breathing pattern in the free-breathing MRE, and a difference between end-expiration and end-inspiration liver stiffness in the breath-held MRE. The promising results demonstrated that the free-breathing and/or breath-hold liver MRE at different breathing states can be useful for the assessment of nonlinear mechanical tissue behaviors.

Purpose

Nonlinear models have been used for distinguishing fibrosis from inflammation in biological tissues, such as bowel in Crohn’s disease [1-3]. However, characterization of this phenomenon in the liver is limited. In this study, we evaluated the feasibility of free-breathing and breath-held liver MRE acquisitions for assessing the nonlinear mechanical response of the liver under varying pre-stressed conditions. Recently, a free-breathing liver MRE acquisition strategy (0.8-second per slice) was developed to acquire 2D multi-slice MRE data without performing breath holds and with greatly reduced overall scan time [4]. During free-breathing, the liver is expected to experience low-frequency (0.1-1 Hz) cyclic strain variations due to respiration with varying amplitude (i.e., depth of breathing) and phase (i.e., state of breathing, such as end-inspiration or end-expiration). We hypothesize that the variation of the conventional 2nd order parameters (e.g., complex shear modulus) measured at standard MRE frequencies (e.g., 30-60 Hz) in response to varying preloads at lower frequency from different breathing states can be used to explore the 3rd order nonlinear mechanical behaviors of the liver tissue.

Methods

With institutional review board approval, 4 healthy volunteers and 2 patients with nonalcoholic fatty liver disease (NAFLD) were imaged on a 1.5T scanner with an 8-channel torso array coil. The standard 19-cm round rigid liver driver was used to delivery vibrations at 30 Hz or 60 Hz. The 2D free-breathing EPI-MRE scans were performed with the subject free-breathing (averaged respiratory rate of ~16-20 breaths per minute). The 3D EPI-MRE scans were performed with a breath hold at the end of expiration and inspiration. The imaging acquisition parameters and post-processing methods were as previously described [4-5]. ROIs were manually drawn in each slice for each acquisition and the distribution of free-breathing, slice-based stiffness estimates were compared to the breath-held results with a two-sample t-test (set P<0.05 as significance level).

Results

In this study, the diaphragm movement during free-breathing varied from 6 mm (shallow fast breathing) to 120 mm (deep slow breathing) across 4 volunteers. Fig.1 illustrates the 2D EPI-MRE results with the different respiration patterns. In the free-breathing acquisition in a healthy volunteer, we observed intriguing stiffness variation (2.3-2.8 kPa, 20%) synchronized with the breathing pattern from an anatomically registered ROI. Fig.2 shows the 3D EPI-MRE results measured at different breath-held positions. In subjects with no or mild steatosis (proton density fat fraction (PDFF) < 15%), the liver stiffness measured at end-inspiration was elevated by 0.25 ± 0.25 kPa (ranging from 0.11 to 0.68 kPa) compared to end-expiration, while the patient with moderate steatosis (PDFF = 21%) had substantially increased liver stiffness of 0.85 kPa (35% increase) compared to the normal stiffness (2.44 kPa) at end-expiration. Volunteers with no or mild steatosis had a decreased damping ratio at 30 Hz of -13.0% ± 4.8% (ranging from -5.4% to -18.4%), while the patient with moderate steatosis had a substantially decreased damping ratio of -35.8%, compared with the end-expiration results. Two representative examples are shown in Fig.3.

Discussion and conclusion

Another collaborative study has confirmed this observation of a difference between end-expiration and end-inspiration liver stiffness using a breath-held 3D EPI MRE, with volumetric liver stiffness being 13% greater at end-inspiration in 9 healthy adults (P<0.05) [6]. Taken together, these findings suggest that inspiration transiently increases liver stiffness, which may augment systematically in diseased livers similar to the postprandial effect or other physiologic activities [7-13]. The promising results demonstrated in this preliminary study suggest that a free-breathing and/or breath-hold liver MRE at different breathing states can be useful for the assessment of nonlinear mechanical tissue behaviors.

Acknowledgements

This research was funded by NIBIB grants EB017197 and EB001981.

References

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[6] Wang K, Manning P, Szeverenyi N, Wolfson T, Hamilton G, Middleton MS, Vaida F, Yin M, Glaser K, Ehman RL, Sirlin CB. Repeatability and reproducibility of 2D and 3D hepatic MR elastography with rigid and flexible drivers at end-expiration and end-inspiration in healthy volunteers. Abdom Radiol (NY). 2017.

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[13] Hu X, Shao J, Bai J, Wang J, Qian L. New noninvasive assessment of liver fibrosis in chronic hepatitis B: maximal accumulative respiration strain. J Ultrasound Med. 2010;29(8):1213-21.

Figures

Fig.1. Changes of liver stiffness measured in 2D EPI-MRE synchronized with different patterns of free-breathing.

Fig.2. Changes of liver stiffness and damping ratio measured at different breath-held positions in breath-held 3D EPI-MRE for 4 healthy volunteers and 2 NAFLD patients. Note that the illustrated stiffness and damping ratio were measured at 60Hz and 30Hz, respectively (PDFF: Proton density fat fraction; BH: breath-held).

Fig.3. Representative wave images and elastograms measured at different breath positions in breath-held 3D EPI-MRE at 60Hz for a healthy volunteer (top) and a NAFLD patient (bottom).

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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