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Six-Dimensional, Free-Breathing Multitasking Multi-Echo (MT-ME) MRI for Whole-Liver T1, PDFF, and R2* Quantification
Nan Wang1, Tianle Cao1,2, Fei Han3, Yibin Xie1, Xiaodong Zhong3, Sen Ma1, Xinheng Zhang1,2, Xiaoming Bi3, Mazen Noureddin4, Vibhas Deshpande3, Anthony G Christodoulou1, and Debiao Li1
1Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States, 2Bioengineering, University of California, Los Angeles, Los Angeles, CA, United States, 3Siemens Medical Solutions USA, Inc., Los Angeles, CA, United States, 4Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States

Synopsis

Chronic liver disease has been a leading cause of mortality worldwide. Multiparametric MRI is a promising tool for non-invasive characterization of liver disease, but has yet to be widely used in clinical practice due to demanding technical challenges. In this work, we proposed a 6D Multitasking multi-echo (MT-ME) technique that allows free-breathing acquisition, whole-liver coverage, and simultaneous T1, PDFF, R2*, and water-specific T1 (T1w) quantification. Phantom study and in vivo studies with 14 volunteers and 1 patient with NAFLD were performed. The quantitative parameters measured from MT-ME were repeatable and showed good agreement with the reference methods.

Introduction

Chronic liver disease is a leading cause of mortality worldwide1. Liver biopsy is the gold standard for diagnosis and staging. However, it is invasive, costly, prone to sampling error, and has a relatively high risk of complications2,3. Recent studies have shown that quantitative markers from multiparametric MRI can serve as a non-invasive approach for liver tissue characterization4. Proton-density fat-fraction (PDFF) and R2* derived from multi-echo GRE can noninvasively quantify fat content and iron overload5-7. Native T1 has been correlated to fibrosis severity with histological validation8-10. Despite the encouraging findings, a standard protocol for clinical use has yet to be established due to practical challenges: 1) compromises among scan time, spatial coverage, and spatial resolution; 2) extra burden on patients due to breath-hold requirements; 3) mis-registration between breath-holds due to separate scans for R2*+FF and T1; 4) confounding factors from fat that may affect the water-specific T1 quantification8. To address the abovementioned limitations, we developed a 6D Multitasking multi-echo (MT-ME) technique that allows free-breathing acquisition, whole-liver coverage, and simultaneous T1, PDFF, R2*, and water-specific T1 (T1w) quantification and performed preliminary studies on volunteers and patients.

Methods

Image acquisition: A custom prototype sequence using a continuous scan with 3D 6-echo bipolar FLASH readouts following periodic non-selective IR preparation was developed to generated T1, water/fat, and R2* contrasts. A stack-of stars sampling pattern with golden-angle rotation in kx-ky plane and Gaussian-density randomized Cartesian reordering in kz dimension incoherently sampled the k-space. A center k-space line in kz dimension was acquired every 8 readouts as training data11.
Image reconstruction: The 6D MT-ME images were represented as a 4-way tensor $$$\mathcal{A}$$$ with voxel location index, IR, multi-echo, and respiratory dimensions. The high correlation along and across multiple image dimensions induces that $$$\mathcal{A}$$$ can be decomposed into the product of different basis matrices representing each dimension12:$$\mathcal{A}=\mathcal{G} \times_{1} \mathbf{U} \times_{2} \mathbf{V} \times_{3} \mathbf{W} \times_{4} \mathbf{Q}$$Where the columns of $$$\mathbf{U}$$$, $$$\mathbf{V}$$$, $$$\mathbf{W}$$$, and $$$\mathbf{Q}$$$ contain the basis functions for spatial, IR, multi-echo, and respiratory dimensions, respectively, and $$$\mathcal{G}$$$ is the core tensor. The reconstruction of the final 6D images can be framed as the recovery of each basis matrix, which are much smaller in size.
Joint T1, PDFF, and R2* quantification: “Joint T1” combining water and fat components was mapped based on the first-echo images at all TIs using the equation in our previous work13. Independently, R2* and PDFF were fitted together using the multi-echo images at the last TI. An in-house algorithm based on variable projection (VARPRO)14 was developed to jointly estimate the proton density for water and fat, field inhomogeneity-related frequency offset, and R2*.
Water-specific T1: To obtain a water-only T1 map, we performed water-fat separation on the low-rank tensor model parameters15. Specifically, we generated a partially-recomposed tensor $$$\mathcal{Y}$$$:$$\mathcal{Y}=\mathcal{G} \times_{1} \mathbf{U} \times_{3} \mathbf{W} \times_{4} \mathbf{Q}=\mathcal{A} \times_{2} \mathbf{V}^{+}$$which multiplies out all model factors except the IR basis $$$ \mathbf{V}$$$, thereby keeping T1 information embedded. The water-fat separation was then performed on $$$\mathcal{Y}$$$ using the abovementioned in-house algorithm, yielding respiratory-motion-resolved water and fat component $$$\mathcal{W}$$$ and $$$\mathcal{F}$$$, respectively. Then $$$\mathcal{A}_{\mathrm{w}}$$$, the water images with multiple TIs, were generated as:$$\mathcal{A}_{\mathrm{w}}=\mathcal{W}\times_{2} \mathbf{V}$$
Subsequently, the T1 mapping was performed on $$$\mathcal{A}_{\mathrm{w}}$$$, producing the water-specific T1, denoted as T1w.
Imaging experiments: All studies were performed on a 3T scanner (MAGNETOM Vida, Siemens Healthcare, Germany) in transversal orientation. In phantom and volunteer (n = 14) studies, MT-ME was performed twice in each imaging session to assess its repeatability; IR-SE sequences without and with water excitation were acquired as T1 reference in phantom; MOLLI16 and q-DIXON7 with breath-hold was used in all in vivo studies as references for T1 and PDFF + R2*, respectively. One patient with nonalcoholic fatty liver disease (NAFLD) was recruited, and MT-ME, MOLLI, and q-DIXON were successfully performed. Table 1 lists the detailed protocols.
Statistical analysis: The repeatability of the parameters estimated using MT-ME was evaluated with Bland-Altman plots and intraclass correlation coefficient (ICC). The Pearson correlation coefficient R was assessed between the parameters quantified from MT-ME and references.

Results

High-quality, co-registered multiparametric maps were generated using MT-ME for all cases. Figure 1 displays the T1, T1w, PDFF, and R2* estimation on the phantom. The ICCs of the four parameters between two repeat MT-ME scans were 0.967, 0.990, 0.997, and 0.983, respectively. The Pearson correlation coefficients (Rs) between MT-ME estimation and references were 0.971, 0.960, 0.998, and 0.986, respectively.
Figure 2 illustrates example T1, T1w, PDFF, and R2* maps of a volunteer. The maps from MT-ME and references were in good agreement. Figure 3(A) displays the Bland-Altman plots for each parameter between two repeat MT-ME measurements for 14 volunteers. The ICCs were 0.988, 0.974, 0.989, and 0.962, respectively. Figure 3(B) shows the correlation of T1, PDFF, and R2* between MT-ME measurement and references. The Rs were 0.990, 0.976, and 0.953, respectively.
Figure 4 shows the multiparametric maps of the patient. There was good consistency between MT-ME and references.

Discussion and Conclusion

This work demonstrated the feasibility of the proposed MT-ME technique for free-breathing simultaneous mapping of T1, PDFF, and R2* with whole liver coverage. The quantitative parameters measured from MT-ME were repeatable and in good agreement with the reference methods.

Acknowledgements

No acknowledgement found.

References

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8. Thompson RB, Chow K, Mager D, Pagano JJ, Grenier J. Simultaneous proton density fat-fraction and R-2* imaging with water-specific T-1 mapping (PROFIT1): application in liver. Magn Reson Med. Aug 4 2020

9. Luetkens JA, Klein S, Traber F, et al. Quantification of Liver Fibrosis at T1 and T2 Mapping with Extracellular Volume Fraction MRI: Preclinical Results. Radiology. Sep 2018;288(3):748-754.

10. Hoad CL, Palaniyappan N, Kaye P, et al. A study of T-1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors. Nmr in Biomedicine. Jun 2015;28(6):706-714.

11. Wang N, Christodoulou AG, Xie Y, Han Fei, Zhong X, Ma S, Bi X, Deshpande V, Li D. Three-Dimensional Free-breathing Whole-Liver Simultaneous T1, R2*, and Fat-Fraction Quantification Using MR Multitasking. In Proceedings of the Annual Meeting of ISMRM, Paris, France, 2020. Abstract 6996

12. Christodoulou AG, Shaw JL, Nguyen C, et al. Magnetic resonance multitasking for motion-resolved quantitative cardiovascular imaging. Nat Biomed Eng. 2018;2(4):215.

13. Wang N, Gaddam S, Wang L, et al. Six-dimensional quantitative DCE MR Multitasking of the entire abdomen: Method and application to pancreatic ductal adenocarcinoma. Magn Reson Med. Aug 2020;84(2):928-948.

14. Hernando D, Haldar JP, Sutton BP, Ma J, Kellman P, Liang ZP. Joint estimation of water/fat images and field inhomogeneity map. Magn Reson Med. Mar 2008;59(3):571-580.

15. Jaubert O, Arrieta C, Cruz G, et al. Multi-parametric liver tissue characterization using MR fingerprinting: Simultaneous T-1, T-2, T-2*, and fat fraction mapping. Mag Reson Med. May 13 2020

16. Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look‐Locker inversion recovery (MOLLI) for high‐resolution T1 mapping of the heart. Magn Reson Med. 2004;52(1):141-146.

Figures

Table 1: List of sequence parameters

Figure 1: Phantom Measurements. (A) T1, T1w, PDFF, and R2* maps from reference sequences and MT-ME. The Inversion-recovery spin-echo (IR-SE) sequence without and with water excitation were used as reference for joint T1 and T1w. q-DIXON provided the reference for PDFF and R2*. The quantitative maps from MT-ME showed great agreement with references. (B) Bland-Altman plots shows good repeatability of T1, T1w, PDFF, and R2* estimated with MT-ME. (C) Good correlation was demonstrated of T1, T1w, PDFF, and R2* from MT-ME and reference with high Pearson correlation coefficient R.

Figure 2: Representative T1, T1w, PDFF, and R2* maps from a 29-year-old volunteers. Good consistency was showed between MT-ME maps and reference. The in vivo T1 reference was 2D MOLLI with a 11-second breath-hold, while the PDFF and R2* reference was q-DIXON with 12-second breath hold. The T1w reference was not available.

Figure 3: (A) Bland-Altman plots demonstrated good in vivo repeatability of the multiparametric mapping from MT-ME. Theoverall inter-scan differences for T1 and T1w were less than 3%, while the differences for PDFF and R2* were less than10%. (B) The regression analysis of T1, PDFF, and R2* measured with MT-ME and references showed good agreement on the 14 volunteers. The Rs was 0.990, 0.976, and 0.953, respectively.

Figure 4: Representative T1, T1w, PDFF, and R2* maps from a 64-year-old patient with NAFLD. The mean T1, PDFF, and R2* of reference were 779 ms, 15.5%, 89 s-1, respectively, while the mean T1, T1w, PDFF, and R2* measured from MT-ME were 785 ms, 643 ms, 15.5%, and 85 s-1.

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)
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