Liver Fat Quantification by Dual-echo MR Imaging Outperforms Traditional Histopathological Analysis

Rationale and Objectives

The aim of this study was to evaluate the accuracy of dual-echo (DE) magnetic resonance imaging (MRI) with and without fat and water separation for the quantification of liver fat content (LFC) in vitro and in patients undergoing liver surgery, with comparison to histopathologic analysis.

Materials and Methods

MRI was performed on a 1.5-T scanner using a three-dimensional DE MRI sequence with automated reconstruction of in-phase (IP) and out-of-phase (OP) and fat-signal-only and water-signal-only images. LFC was estimated by fat fractions from IP and OP images (MRI IP/OP ) and from Dixon-based fat-only and water-only images (MRI DIxON ). Seven phantoms containing a titrated mixture of liver and fat from 0% to 50% were examined. Forty-three biopsies in 22 patients undergoing liver surgery were prospectively evaluated by a pathologist by traditional determination of the cell-count fraction and by a computer-based algorithm, the latter serving as the reference standard.

Results

In vitro, both MRI IP/OP and MRI DIxON were significantly correlated with titrated LFC ( r = 0.993, P < .001), with a smaller measurement bias for MRI IP/OP (+2.6%) than for MRI DIxON (+4.5%). In vivo, both MRI IP/OP and MRI DIxON from DE MRI were correlated significantly better with computer-based histologic results ( P < .001) and showed significantly smaller measurement bias (4.8% vs 21.1%) compared to histologic cell-count fraction ( P < .001). Measurement bias was significantly smaller for MRI IP/OP than for MRI DIxON ( P < .001).

Conclusions

DE MRI allows the accurate quantification of LFC in a surgical population, outperforming traditional histopathologic analysis. DE MRI without fat and water separation shows the highest accuracy and smallest measurement bias for the quantification of LFC.

Fatty liver disease is a risk factor for the development of end-stage liver disease as well as for postoperative complications after liver surgery and liver transplantation . To date, the visual assessment of liver tissue by an experienced pathologist is the reference standard for the quantification of liver fat content (LFC) . However, histopathologic analysis on the basis of counts of liver cells containing fat vacuoles is subject to considerable interreader variability and therefore does not allow reliable risk evaluation before surgical intervention . Recent developments using computer-based algorithms for quantitative histopathologic analysis of the fat-area fraction have shown less variability and higher accuracy for the quantification of LFC but are technically demanding and also require biopsy.

Dual-echo (DE) magnetic resonance imaging (MRI) at in-phase (IP) and out-of-phase (OP) echo times is commonly used to noninvasively assess steatosis in routine clinical practice. In contrast to recently introduced multiple-echo MRI, DE MRI is confounded by the so-called T2* bias induced by local field inhomogeneities caused by coexisting iron accompanying liver cirrhosis and other diffuse liver diseases .

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Materials and methods

MRI

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LFC Quantification Algorithm

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MRIDIXON=SIFAT/(SIFAT+SIWATER), MRI

DIXON

=

SI

FAT

/

(

SI

FAT

+

SI

WATER

)

,

where SI FAT is the signal intensity derived from fat-only images and SI WATER is the signal intensity derived from water-only images, and

MRIIP/OP=(SIIP±SIOP)/(2SIIP), MRI

IP

/

OP

=

(

SI

IP

±

SI

OP

)

/

(

2

SI

IP

)

,

where SI IP is the signal intensity derived from IP images and SI OP is the signal intensity derived from OP images.

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Phantom Study

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Data Analysis

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Patient Study

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Table 1

Patient Demographics (n = 51)

Variable Value Men 31 (61%) Women 20 (39%) Age (y), mean ± standard deviation 64 ± 21 Reason for surgery Primary liver lesion 32 (63%) Hemangioma 2 (4%) Focal nodular hyperplasia 2 (4%)Echinococcus multilocularis 3 (6%) Hepatocellular adenoma 4 (8%) Gallbladder/cholangiocellular carcinoma 8 (16%) Hepatocellular carcinoma 13 (26%) Liver metastases 19 (37%) Medical history Asymptomatic 10 (20%) Symptomatic 41 (80%) Hepatitis 9 (18%) Jaundice 10 (20%) Other 32 (63%) Neoadjuvant therapy 11 (22%) Chemotherapy 9 (18%) Radiotherapy 2 (4%)

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Magnetic Resonance Image Analysis

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Histopathology

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Visual assessment

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Fat fraction

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Statistical Analysis

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Results

Phantom Study

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Table 2

Interobserver Agreement for In Vitro and In Vivo Magnetic Resonance Imaging Fat Measurements

Interobserver Agreement Correlation Bland-Altman Analysis Pearson’s Correlation Coefficient ( r ) Linear Regression Coefficient ( R 2 ) Mean Bias Limits of Agreement In vitro MRI IP/OP 0.994 0.999 0.2% −1.8% to 2.2% MRI DIxON 0.994 0.998 0.2% −2.1% to 2.7% In vivo MRI IP/OP 0.983 0.982 0.4% −2.5% to 1.7% MRI DIxON 0.951 0.967 0.5% −2.9% to 1.8%

MRI DIxON , magnetic resonance imaging fat fractions derived from Dixon-based fat-only and water-only images; MRI IP/OP , magnetic resonance imaging fat fractions derived from in-phase and out-of-phase images.

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Patient Study

Histopathology

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MRI

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Discussion

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Conclusions

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