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

Karlsson, Maria; Ekstedt, Mattias; Dahlström, Nils; Forsgren, Mikael; Ignatova, Simone; Norén, Bengt; Leinhard, Olof Dahlqvist; Kechagias, Stergios; Lundberg, Peter

doi:10.1002/jmri.26601

Cited by 29 publications

(37 citation statements)

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“…The most common method to quantify R2* is to acquire T2*-weighted gradient echo images with different TE [49][50][51] (Figure 4.1). Ideally, the signal from these images should decrease monoexponentially as a function of TE:…”

Section: R2*-mappingmentioning

confidence: 99%

“…This method is easy, but it does have the drawbacks of not addressing the signal from the full fat spectrum (Figure 3.2), as well as forcing the use of longer TEs. Many authors recommend using a minimum TE around 1 ms [53,60,61], while the shortest in-phase TE is 4.6 ms at 1.5 T. The second method is to acquire images with fat saturation [49]. Again, this is also a simple solution, but it can have a problem if the fat suppression is imperfect.…”

Section: Fatmentioning

confidence: 99%

“…On the other hand, a longer TE may not be a problem if the patient group being studied is not expected to have severe iron overload. This could be the case, for example, when assessing if NAFLD patients, or other patients with different chronic liver diseases, have concomitant iron overload [49,65,67]. In such cases the longer TEs could be enough.…”

Section: R2* Vs R2mentioning

confidence: 99%

“…The different markers indicate the Perls' score given by the histopathologist. The black line is a linear regressionReproduced and modified from:Karlsson et al (2019), Liver R2* is affected by both iron and fat: A dual biopsy-validated study of chronic liver disease. J. Magn.…”

mentioning

confidence: 99%

“…Reproduced from:Karlsson et al (2019), Is Liver Function Affected by Biliary Stenoses? -Hepatocyte Uptake in Primary Sclerosing Cholangitis Determined Using Gadoxetate Enhanced Magnetic Resonance.…”

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confidence: 99%

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Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance

Karlsson

2020

Linköping University Medical Dissertations

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There is a large and unmet need for diagnostic tool that can be used to characterize chronic liver diseases (CLD). In the earlier stages of CLD, much of the diagnostics involves performing biopsies, which are evaluated by a histopathologist for the presence of e.g. fat, iron, inflammation, and fibrosis. Performing biopsies, however, have two downsides: i) biopsies are invasive and carries a small but non-negligible risk for serious complications, ii) biopsies only represents a tiny portion of the liver and are thus prone to sampling error. Moreover, in the later stages of CLD, when the disease has progressed far enough, the ability of the liver to perform its basic function will be compromised. In this stage, there is a need for better methods for accurately measuring liver function. Additionally, measures of liver function can also be used when developing new drugs, as biomarkers for drug-induced liver injury (DILI), which is a serious drug-safety issue. Magnetic resonance imaging (MRI) is a non-invasive medical imaging modality, which have shown much promise with regards to characterizing liver disease in all of the above-mentioned aspects. The aim of this PhD project was to develop and validate MR-based methods that can be used to non-invasively characterize liver disease. Paper I investigated if R2* mapping, a MR-method for measuring liver iron content, can be confounded by liver fat. The results show fat does affect R2*. The conclusion was therefore that fat must be taken into account when measuring small amounts of liver iron, as a small increase in R2* could be due to either small amounts of iron or large amounts of fat. Paper II examined whether T1 mapping, which is another MR-method, can be used for staging liver fibrosis. The results of previous research have been mixed; some studies have been very promising, whereas other studies have been less promising. Unfortunately, the results in Paper II belongs to the less promising studies. Paper III focused on measuring liver function by dynamic contrast-enhanced MRI (DCE-MRI) using a liver specific contrast agent, which is taken up the hepatocytes and excreted to the bile. The purpose of the paper was to extend and validate a method for estimating uptake and efflux rates of the contrast agent. The method had previously only been applied in health volunteers. Paper II showed that the method can be applied to CLD patients and that the uptake of the contrast agent is lower in patients with advanced fibrosis.

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Section: R2*-mappingmentioning

confidence: 99%

Section: Fatmentioning

confidence: 99%

Section: R2* Vs R2mentioning

confidence: 99%

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Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance

Karlsson

2020

Linköping University Medical Dissertations

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Hepatic Iron Quantification Using a Free‐Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy‐Calibrated R₂^* Relaxometry Method

Rohani

Morin

Zhong

et al. 2021

Magnetic Resonance Imaging

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Background: Hepatic iron content (HIC) is an important parameter for the management of iron overload. Non-invasive HIC assessment is often performed using biopsy-calibrated two-dimensional breath-hold Cartesian gradient echo (2D BH GRE) R 2 * -MRI. However, breath-holding is not possible in most pediatric patients or those with respiratory problems, and three-dimensional free-breathing radial GRE (3D FB rGRE) has emerged as a viable alternative. Purpose: To evaluate the performance of a 3D FB rGRE and validate its R 2 * and fat fraction (FF) quantification with 3D breath-hold Cartesian GRE (3D BH cGRE) and biopsy-calibrated 2D BH GRE across a wide range of HICs. Study Type: Retrospective. Subjects: Twenty-nine patients with hepatic iron overload (22 females, median age: 15 [5-25] years). Field Strength/Sequence: Three-dimensional radial and 2D and 3D Cartesian multi-echo GRE at 1.5 T. Assessment: R 2 * and FF maps were computed for 3D GREs using a multi-spectral fat model and 2D GRE R 2 * maps were calculated using a mono-exponential model. Mean R 2 * and FF values were calculated via whole-liver contouring and T 2 *thresholding by three operators. Statistical Tests: Inter-and intra-observer reproducibility was assessed using Bland-Altman and intraclass correlation coefficient (ICC). Linear regression and Bland-Altman analysis were performed to compare R 2 * and FF values among the three acquisitions. One-way repeated-measures ANOVA and Wilcoxon signed-rank tests, respectively, were used to test for significant differences between R 2 * and FF values obtained with different acquisitions. Statistical significance was assumed at P < 0.05. Results: The mean biases and ICC for inter-and intra-observer reproducibility were close to 0% and >0.99, respectively for both R 2 * and FF. The 3D FB rGRE R 2 * and FF values were not significantly different (P > 0.44) and highly correlated (R 2 ≥ 0.98) with breath-hold Cartesian GREs, with mean biases ≤ AE2.5% and slopes 0.90-1.12. In non-breath-holding patients, Cartesian GREs showed motion artifacts, whereas 3D FB rGRE exhibited only minimal streaking artifacts. Data Conclusion: Free-breathing 3D radial GRE is a viable alternative in non-breath-hold patients for accurate HIC estimation.

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Design and evaluation of quantitative MRI phantoms to mimic the simultaneous presence of fat, iron, and fibrosis in the liver

Zhao

Hamilton

Brittain

et al. 2020

Magnetic Resonance in Med

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Purpose To design, construct, and evaluate quantitative MR phantoms that mimic MRI signals from the liver with simultaneous control of three parameters: proton‐density fat fraction (PDFF), R2∗, and T1. These parameters are established biomarkers of hepatic steatosis, iron overload, and fibrosis/inflammation, respectively, which can occur simultaneously in the liver. Methods Phantoms including multiple vials were constructed. Peanut oil was used to modulate PDFF, MnCl2 and iron microspheres were used to modulate R2∗, and NiCl2 was used to modulate the T1 of water (T1,water). Phantoms were evaluated at both 1.5 T and 3 T using stimulated‐echo acquisition‐mode MRS and chemical shift–encoded MRI. Stimulated‐echo acquisition‐mode MRS data were processed to estimate T1,water, T1,fat, R2,water∗, and R2,fat∗ for each vial. Chemical shift–encoded MRI data were processed to generate PDFF and R2∗ maps, and measurements were obtained in each vial. Measurements were evaluated using linear regression and Bland‐Altman analysis. Results High‐quality PDFF and R2∗ maps were obtained with homogeneous values throughout each vial. High correlation was observed between imaging PDFF with target PDFF (slope = 0.94‐0.97, R2 = 0.994‐0.997) and imaging R2∗ with target R2∗ (slope = 0.84‐0.88, R2 = 0.935‐0.943) at both 1.5 T and 3 T. The values of R2,fat∗ and R2,water∗ were highly correlated with slope close to 1.0 at both 1.5 T (slope = 0.90, R2 = 0.988) and 3 T (slope = 0.99, R2 = 0.959), similar to the behavior observed in vivo. The value of T1,water (500‐1200 ms) was controlled with varying NiCl2 concentration, while T1,fat (300 ms) was independent of NiCl2 concentration. Conclusion Novel quantitative MRI phantoms that mimic the simultaneous presence of fat, iron, and fibrosis in the liver were successfully developed and validated.

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

Cited by 29 publications

References 29 publications

Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance

Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance

Hepatic Iron Quantification Using a Free‐Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy‐Calibrated R₂^* Relaxometry Method

Design and evaluation of quantitative MRI phantoms to mimic the simultaneous presence of fat, iron, and fibrosis in the liver

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

Cited by 29 publications

References 29 publications

Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance

Non-Invasive Characterization of Liver Disease : By Multimodal Quantitative Magnetic Resonance

Hepatic Iron Quantification Using a Free‐Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy‐Calibrated R2* Relaxometry Method

Design and evaluation of quantitative MRI phantoms to mimic the simultaneous presence of fat, iron, and fibrosis in the liver

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Hepatic Iron Quantification Using a Free‐Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy‐Calibrated R₂^* Relaxometry Method