Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis

Qu, Yue; Middleton, Michael S.; Loomba, Rohit; Glaser, Kevin J.; Hooker, Jonathan; Wolfson, Tanya; Covarrubias, Yesenia; Valasek, Mark A.; Fowler, Kathryn J.; Zhang, Yingzhen; Sy, Ethan; Gamst, Anthony; Wang, Kang; Mamidipalli, Adrija; Schwimmer, Jeffrey B.; Song, Bin; Reeder, Scott B.; Yin, Meng; Ehman, Richard L.; Sirlin, Claude B.

doi:10.1007/s00330-021-07988-6

Cited by 9 publications

(16 citation statements)

References 39 publications

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“…Itoh et al 31 measured 2D in‐plane stiffness values of 2.47 ± 0.11 kPa in volunteers at 60 Hz, with only one encoding direction, which was slightly higher than our reported 3D stiffness value of 2.19 ± 0.28 kPa. Previous studies have reported similar differences in the liver and brain using 2D and 3D MRE 32,33 . We speculate that through‐plane propagating waves may appear in 2D data as waves with longer wavelengths, thereby resulting in a slight overestimation of tissue stiffness.…”

Section: Discussionmentioning

confidence: 52%

“…Previous studies have reported similar differences in the liver and brain using 2D and 3D MRE. 32,33 We speculate that throughplane propagating waves may appear in 2D data as waves with longer wavelengths, thereby resulting in a slight overestimation of tissue stiffness. The overall mean shear stiffness of PDAC in our study was 3.50 AE 0.34 kPa at 40 Hz, which was similar to the results obtained in 43 patients with PDAC reported by Shi et al (3.30 kPa).…”

Section: Discussionmentioning

confidence: 95%

“…Moreover, elastograms at 40 Hz had better spatial resolution compared to those at 30 Hz when imaging the normal pancreas. Diagnostic IQS in healthy volunteers was independently associated with lower BMI, shorter wave distance, and lower frequencies (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). In patients with PDAC, MRE at 30-60 Hz generated diagnostic wave images in no less than 80% of PDACs.…”

Section: Discussionmentioning

confidence: 99%

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Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases

Song

Shi

Gao

et al. 2022

Magnetic Resonance Imaging

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Background: The feasibility and reproducibility of multifrequency MR elastography (MRE) for diagnosing pancreatic ductal adenocarcinoma (PDAC) have not been reported. Purpose: To determine the feasibility and reproducibility of multifrequency MRE for assessing pancreatic stiffness in healthy and diseased pancreases. Study type: Prospective. Subjects: A total of 40 healthy volunteers and 10 patients with PDAC were prospectively recruited between March 2018 and October 2021. Field strength/sequence: A 3.0-T pancreatic MRE at frequencies in the order of 30, 40, 60, 80, and 100 Hz. Assessment: Body mass index (BMI) and wave distance of the healthy pancreas and PDAC were measured. Image quality was assessed using the image quality score (IQS: 1-4, ≥3 were considered diagnostic quality). Three readers independently performed the pancreatic stiffness and IQS assessments to evaluate reproducibility. Statistical tests: Logistic regression analyses were performed to determine variables that influenced IQS. Statistical significance was set at P <0.05. Levels of inter-and intrarater agreement were assessed using intraclass correlation coefficients (ICC) and Cohen's kappa coefficient (κ). Good reproducibility was set at ICC and κ ≥ 0.8. Results: In logistic regression analysis, a diagnostic IQS in healthy volunteers was independently associated with a lower BMI (odds ratio [OR] = 0.89 kg/m À2 ), shorter wave distance (OR = 0.70 cm À1 ), and lower frequency (30 and 40 Hz: OR = 170.01 and 96.02). In PDAC, frequency was the only independent factor for diagnostic IQS 46.18, and 17.20, respectively) with 100 Hz as a reference. In healthy volunteers, good reproducibility was observed at 30 and 40 Hz. In PDAC, good reproducibility was observed at 30-60 Hz. Data conclusion: MRE at 30 and 40 Hz provides diagnostic wave images and reliable measurements of pancreatic stiffness in healthy volunteers. MRE at 30-60 Hz is acceptable for PDACs (IQS ≥ 3, ICC and κ ≥ 0.80).

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases

Song

Shi

Gao

et al. 2022

Magnetic Resonance Imaging

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“…However, PET scans are expensive, they result in exposure of the patient to ionizing radiation and they address only specific metabolic pathways that are not necessarily fully suited for assessment of the liver’s metabolic capacity. Ultrasound-based elastography and magnetic resonance elastography (MRE) have become successful in addressing structural changes such as like degree of fibrosis and steatosis, and they therefore have the potential to replace biopsy-based histological evaluation of structural alteration ( Singh et al, 2015 ; Castera et al, 2019 ; Hudert et al, 2021 ; Qu et al, 2021 ; Selvaraj et al, 2021 ). Liver fibrosis increases liver stiffness through accumulation and cross-linking of matrix proteins ( Huwart et al, 2008 ; Singh et al, 2015 ; Reiter et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Liver fibrosis increases liver stiffness through accumulation and cross-linking of matrix proteins ( Huwart et al, 2008 ; Singh et al, 2015 ; Reiter et al, 2020 ). However, beyond fibrosis, the liver’s biomechanical properties are also affected by non-fibrotic alterations such as prandial states ( Yin et al, 2011 ; Jajamovich et al, 2014 ; Petzold et al, 2019 ; Obrzut et al, 2021 ), hydration ( Ipek-Ugay et al, 2016 ; Dittmann et al, 2017 ), blood perfusion ( Ipek-Ugay et al, 2016 ; Meyer et al, 2022a ), cell hypertrophy ( Garczyńska et al, 2020 ), fat accumulation ( Hudert et al, 2019 ) or inflammation ( Qu et al, 2021 ; Selvaraj et al, 2021 ), making elastography unspecifically sensitive to a variety of pathophysiological processes that occur in the course of NAFLD. Only little is known about the correlation between liver biomechanical parameters and liver metabolism.…”

Section: Introductionmentioning

confidence: 99%

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

Shahryari

Keller

Meierhofer

et al. 2023

Front. Bioeng. Biotechnol.

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The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver’s metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver’s metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography–mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into ‘stiff’ and ‘soft’ subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.

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Visco‐Elastic Parameters at Three‐Dimensional MR Elastography for Diagnosing Non‐Alcoholic Steatohepatitis and Substantial Fibrosis in Mice

Khalfallah

Doblas

Hammoutène

et al. 2023

Magnetic Resonance Imaging

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BackgroundNonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is a growing cause of liver cirrhosis and cancer. The performance of the magnetic resonance elastography (MRE) visco‐elastic parameters in diagnosing progressive forms of NAFLD, including nonalcoholic steatohepatitis (NASH) and substantial fibrosis (F ≥ 2), needs to be clarified.PurposeTo assess the value of three‐dimensional MRE visco‐elastic parameters as markers of NASH and substantial fibrosis in mice with NAFLD.Study TypeProspective.Animal ModelTwo mouse models of NAFLD were induced by feeding with high fat diet or high fat, choline‐deficient, amino acid‐defined diet.Field Strength/Sequence7T/multi‐slice multi‐echo spin‐echo MRE at 400 Hz with motion encoding in the three spatial directions.AssessmentHepatic storage and loss moduli were calculated. Histological analysis was based on the NASH Clinical Research Network criteria.Statistical TestsMann–Whitney, Kruskal–Wallis tests, Spearman rank correlations and multiple regressions were used. Diagnostic performance was assessed with areas under the receiver operating characteristic curves (AUCs). P value <0.05 was considered significant.ResultsAmong the 59 mice with NAFLD, 21 had NASH and 20 had substantial fibrosis (including 8 mice without and 12 mice with NASH). The storage and loss moduli had similar moderate accuracy for diagnosing NASH with AUCs of 0.67 and 0.66, respectively. For diagnosing substantial fibrosis, the AUC of the storage modulus was 0.73 and the AUC of the loss modulus was 0.81, indicating good diagnostic performance. Using Spearman correlations, histological fibrosis, inflammation and steatosis, but not ballooning, were significantly correlated with the visco‐elastic parameters. Using multiple regression, fibrosis was the only histological feature independently associated with the visco‐elastic parameters.ConclusionMRE in mice with NAFLD suggests that the storage and loss moduli have good diagnostic performance for detecting progressive NAFLD defined as substantial fibrosis rather than NASH.Evidence Level1Technical Efficacy Stage2

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Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis

Cited by 9 publications

References 39 publications

Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases

Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

Visco‐Elastic Parameters at Three‐Dimensional MR Elastography for Diagnosing Non‐Alcoholic Steatohepatitis and Substantial Fibrosis in Mice

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