Cross‐sectional correlation between hepatic R2* and proton density fat fraction (PDFF) in children with hepatic steatosis

Mamidipalli, Adrija; Hamilton, Gavin; Manning, Paul; Hong, Cheng William; Park, Charlie C.; Wolfson, Tanya; Hooker, Jonathan; Heba, Elhamy; Schlein, Alexandra; Gamst, Anthony; Durelle, Janis; Paiz, Melissa; Middleton, Michael S.; Schwimmer, Jeffrey B.; Sirlin, Claude B.

doi:10.1002/jmri.25748

Cited by 20 publications

(30 citation statements)

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“…We investigated whether R2* was associated with fat accumulation, which has previously been reported . Figure shows the correlation between R2* and PDFF, measured by MRS.…”

Section: Resultsmentioning

confidence: 76%

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Liver R2* is affected by both iron and fat: A dual biopsy‐validated study of chronic liver disease

Karlsson

Ekstedt

Dahlström

et al. 2019

Magnetic Resonance Imaging

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Background Liver iron content (LIC) in chronic liver disease (CLD) is currently determined by performing an invasive liver biopsy. MRI using R2* relaxometry is a noninvasive alternative for estimating LIC. Fat accumulation in the liver, or proton density fat fraction (PDFF), may be a possible confounder of R2* measurements. Previous studies of the effect of PDFF on R2* have not used quantitative LIC measurement. Purpose To assess the associations between R2*, LIC, PDFF, and liver histology in patients with suspected CLD. Study Type Prospective. Population Eighty‐one patients with suspected CLD. Field Strength/Sequence 1.5 T. Multiecho turbo field echo to quantify R2*. PRESS MRS to quantify PDFF. Assessment Each patient underwent an MR examination, followed by two needle biopsies immediately following the MR examination. The first biopsy was used for conventional histological assessment of LIC, whereas the second biopsy was used to quantitatively measure LIC using mass spectrometry. R2* was correlated with both LIC and PDFF. A correction for the influence of fat on R2* was calculated. Statistical Tests Pearson correlation, linear regression, and area under the receiver operating curve. Results There was a positive linear correlation between R2* and PDFF (R = 0.69), after removing data from patients with elevated iron levels, as defined by LIC. R2*, corrected for PDFF, was the best method for identifying patients with elevated iron levels, with a correlation of R = 0.87 and a sensitivity and specificity of 87.5% and 98.6%, respectively. Data Conclusion PDFF increases R2*. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:325–333.

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“…We investigated whether R2* was associated with fat accumulation, which has previously been reported . Figure shows the correlation between R2* and PDFF, measured by MRS.…”

Section: Resultsmentioning

confidence: 76%

“…Recently, both Mamidipalli et al and Bashir et al reported that fat accumulation in the liver correlates with a slight increase in liver R2*. Although the exact mechanism is unknown, Mamidipalli et al hypothesized that, similar to iron, hepatic fat droplets induce local susceptibility effects, leading to an increased R2*.…”

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confidence: 99%

Liver R2* is affected by both iron and fat: A dual biopsy‐validated study of chronic liver disease

Karlsson

Ekstedt

Dahlström

et al. 2019

Magnetic Resonance Imaging

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“…The relationship between R2* and PDFF was examined using Pearson's correlation, since a linear relationship had been found in previous works . This analysis was repeated for the subset of subjects with and without hepatocellular or nonhepatocellular iron at each field strength, and Spearman's correlation was used if the relationship appeared nonlinear and/or numerous outliers were present .…”

Section: Methodsmentioning

confidence: 99%

“…To date, two retrospective single‐center studies by Bashir et al and Mamidipalli et al have independently shown that liver PDFF and R2* values are positively correlated in vivo at 3T magnetic resonance imaging (MRI) in populations without iron overload . Although limited by lack of histological correlation, these studies suggest that in patients without risk factors for severe iron overload (eg, patients with NAFLD), R2* may not be an unconfounded measure of liver iron.…”

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confidence: 99%

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease

Bashir

Wolfson

Gamst

et al. 2018

Magnetic Resonance Imaging

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Background The liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates. Purpose To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). Study Type Retrospective analysis of prospectively acquired data. Population Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials. Field Strength 1.5T and 3T; chemical‐shift encoded multiecho gradient echo. Assessment Correlation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI‐derived, and histological covariates of liver R2*. Statistical Tests Pearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine‐learning method. Results Hepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P < 0.0001) and at 3T (r = 0.586, P < 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength. Data Conclusion Hepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only. Level of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456–1466.

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“…The linear term c 1 is compatible with the effects of susceptibility‐induced dephasing caused by the difference in magnetic susceptibility between water and fat. Previous studies have reported a positive correlation between PDFF and R 2 * with slopes of between 25 and ≈100 s −1 . R 2 * in these studies is a monoexponential approximation of the decay and therefore not directly comparable with c 1 .…”

Section: Discussionmentioning

confidence: 85%

Sources of systematic error in proton density fat fraction (PDFF) quantification in the liver evaluated from magnitude images with different numbers of echoes

et al. 2017

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DK088925The purpose of this work was to investigate sources of bias in magnetic resonance imaging (MRI) liver fat quantification that lead to a dependence of the proton density fat fraction (PDFF) on the number of echoes. This was a retrospective analysis of liver MRI data from 463 subjects. The magnitude signal variation with TE from spoiled gradient echo images was curve fitted to estimate the PDFF using a model that included monoexponential R 2 * decay and a multi-peak fat spectrum.Additional corrections for non-exponential decay (Gaussian), bi-exponential decay, degree of fat saturation, water frequency shift and noise bias were introduced. The fitting error was minimized with respect to 463 × 3 = 1389 subject-specific parameters and seven additional parameters associated with these corrections. The effect on PDFF was analyzed, notably the dependence on the number of echoes. The effects on R 2 * were also analyzed. The results showed that the inclusion of bias corrections resulted in an increase in the quality of fit (r 2 ) in 427 of 463 subjects (i.e. 92.2%) and a reduction in the total fitting error (residual norm) of 43.6%. This was largely a result of the Gaussian decay (57.8% of the reduction), fat spectrum (31.0%) and biexponential decay (8.8%) terms. The inclusion of corrections was also accompanied by a decrease in the dependence of PDFF on the number of echoes. Similar analysis of R 2 * showed a decrease in the dependence on the number of echoes. Comparison of PDFF with spectroscopy indicated excellent agreement before and after correction, but the latter exhibited lower bias on a Bland-Altman plot (1.35% versus 0.41%). In conclusion, correction for known and expected biases in PDFF quantification in liver reduces the fitting error, decreases the dependence on the number of echoes and increases the accuracy. | INTRODUCTIONQuantitative measures of the fat content in liver are increasingly being used as biological markers of non-alcoholic fatty liver disease (NAFLD) and other metabolic disorders. [1][2][3][4] Qualitative evaluation of the fat content using magnetic resonance imaging (MRI) has been routinely used for a long time by assessing the difference between the in-phase (IP) and opposed-phase (OP) images. 5,6 Abbreviations used: FA, flip angle; FOV, field of view; HIPAA, Health Insurance Portability and Accountability Act; IP, in-phase; IRB, Institutional Review Board; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; NAFLD, non-alcoholic fatty liver disease; ndb, number of double bonds; OP, opposed-phase; PDFF, proton density fat fraction; ROI, region of interest; SNR, signal-to-noise ratio; SPGR, spoiled gradient recalled-echo; STEAM, stimulated echo acquisition mode However, qualitative and semi-quantitative methods are difficult to standardize and can be implementation dependent, which can complicate the use of MRI for the monitoring of patients over time, especially if they are scanned on different scanners or with different techniques. Thus, there are advantages to...

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Cross‐sectional correlation between hepatic R2* and proton density fat fraction (PDFF) in children with hepatic steatosis

Abstract: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:418-424.

Cited by 20 publications

References 38 publications

Liver R2* is affected by both iron and fat: A dual biopsy‐validated study of chronic liver disease

Liver R2* is affected by both iron and fat: A dual biopsy‐validated study of chronic liver disease

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease

Sources of systematic error in proton density fat fraction (PDFF) quantification in the liver evaluated from magnitude images with different numbers of echoes

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