Background: Three-dimensional (3D) MR elastography (MRE) derives viscoelastic parameters that may reflect inflammation, but their frequency dependence and the influence of steatosis on inflammation grading and fibrosis staging remain unclear.

Purpose: To investigate 3D multifrequency MRE for assessing hepatic inflammation, fibrosis stage across frequencies, and the influence of steatosis.

Study Type: Prospective.

Population: Sixty-four (40 men, median age: 58 years) participants with chronic liver disease (CLD); 21 (8 men, median age:28 years) healthy volunteers.

Field Strength/Sequence: 3-T; gradient-echo sequence with mechanical vibrations at low (16.7 and 18 Hz), medium (33.4 and 36 Hz), and high (50.1 and 54 Hz) frequencies.

Assessment: In CLD participants, MRE-derived viscoelastic parameters, shear stiffness, storage modulus, loss modulus, and damping ratio were compared with histologically assessed fibrosis, inflammation, and steatosis. MRE test–retest repeatability over 10 min was evaluated in healthy volunteers.

Statistical Tests: Wilcoxon rank sum test, Spearman's correlation, multivariable regression analysis, and area under the receiver operating curve (AUROC). A p value of < 0.05 was considered statistically significant.

Results: Inflammation was significantly independently associated with damping ratio at medium frequency, which showed moderate performance for grading inflammation (AUROC = 0.76–0.83, sensitivity = 0.83–0.84, specificity = 0.70–0.79). Fibrosis staging using shear stiffness and moduli showed high diagnostic performance (AUROC = 0.82–0.95), with comparable accuracy between medium and high frequencies (p = 0.327–0.896). Steatosis was not significantly correlated with MRE overall (p = 0.212–0.459), but was significantly associated with 19% higher stiffness and 20% higher loss modulus at medium frequency in CLD participants without fibrosis or inflammation.

Data Conclusion: Medium frequency 3D MRE demonstrated an independent association with inflammation while preserving accurate fibrosis assessment. Steatosis seemed not to confound MRE-based evaluation.

Level of Evidence: 1.

Technical Efficacy: Stage 2.

Plain Language Summary: Chronic liver disease can cause both inflammation and scarring (fibrosis). Accurate assessment usually requires a biopsy, which is invasive. This study evaluated a noninvasive imaging method called three-dimensional magnetic resonance elastography (3D MRE) in patients who underwent same-day liver biopsy. The researchers tested whether different vibration frequencies could detect inflammation and fibrosis. They found that medium frequency measurements were associated with liver inflammation while still accurately identifying fibrosis. Fat accumulation in the liver did not significantly affect the results. These findings suggest that 3D MRE may help medical doctors assess liver inflammation and fibrosis noninvasively in a single examination.

Objective: Primary sclerosing cholangitis (PSC) is a rare broin ammatory hepatobiliary disease with a highly variable clinical course. Identifying patients at risk for poor outcomes remains challenging. Magnetic resonance imaging (MRI)-based approaches such as DiStrict, Anali score, and relative enhancement (RE) show promise but are limited by operator dependency or static measurements. This study explored pharmacokinetic modelling of liver function as a quantitative imaging biomarker for risk assessment in PSC.

Materials and methods: A prospective cohort of 26 PSC patients underwent up to ve annual MRI examinations with follow-up up to 7.5 years. Clinical endpoints included liver transplantation, decompensated cirrhosis, and cholangiocarcinoma. Correlation and receiver operating characteristics (ROC) analyses compared the pharmacokinetic model with Anali scores, RE, model for end-stage liver disease (MELD), and the Amsterdam–Oxford Model (AOM).

Results: The pharmacokinetic model (ksingle) correlated signi cantly with MELD (r = -0.429, p= 0.029), AOM (r = -0.557, p= 0.003), and endpoint events (r = -0.605, p= 0.001). ROC analysis showed excellent discrimination for ki,single (area under the curve [AUC]= 0.943) outperformed Anali scores (AUC= 0.800–0.829) and comparable to MELD (AUC= 0.857) and AOM (AUC= 0.900).

Conclusion: Pharmacokinetic liver function modelling correlated strongly with MELD and AOM, effectively identifying high-risk PSC patients.

Relevance statement: Pharmacokinetic liver function modelling detects functional impairment in PSC, correlating well with established tools such as the AOM. As an objective, quantitative imaging biomarker, this method may complement established risk scores and aid in the identi cation of patients at risk of adverse outcomes.

Key Points:

● Pharmacokinetic modelling estimates changes in liver function based on MRI.

● These estimates can be used as a prognostic tool in PSC.

● The model’s prognostic performance was comparable to established clinical tests.

BACKGROUND: Drug induced liver injury (DILI) is a major concern when developing new drugs. A promising biomarker for DILI is the hepatic uptake rate of the contrast agent gadoxetate. This rate can be estimated using a novel approach combining magnetic resonance imaging and mathematical modeling. However, previous work has used different mathematical models to describe liver function in humans or rats, and no comparative study has assessed which model is most optimal to use, or focused on possible translatability between the two species.

AIMS: Our aim was therefore to do a comparison and assessment of models for DILI biomarker assessment, and to develop a conceptual basis for a translational framework between the species.

METHODS AND RESULTS: We first established which of the available pharmacokinetic models to use by identifying the most simple and identifiable model that can describe data from both human and rats. We then developed an extension of this model for how to estimate the effects of a hepatotoxic drug in rats. Finally, we illustrated how such a framework could be useful for drug dosage selection, and how it potentially can be applied in personalized treatments designed to avoid DILI.

CONCLUSION: Our analysis provides clear guidelines of which mathematical model to use for model-based assessment of biomarkers for liver function, and it also suggests a hypothetical path to a translational framework for DILI.

BackgroundNon-alcoholic fatty liver disease (NAFLD) affects 20-30% of the general adult population. NAFLD patients with type 2 diabetes mellitus (T2DM) are at an increased risk of advanced fibrosis, which puts them at risk of cardiovascular complications, hepatocellular carcinoma, or liver failure. Liver biopsy is the gold standard for assessing hepatic fibrosis. However, its utility is inherently limited. Consequently, the prevalence and characteristics of T2DM patients with advanced fibrosis are unknown. Therefore, the purpose of the current study is to evaluate the prevalence and severity of NAFLD in patients with T2DM by recruiting participants from primary care, using the latest imaging modalities, to collect a cohort of well phenotyped patients.MethodsWe will prospectively recruit 400 patients with T2DM using biomarkers to assess their status. Specifically, we will evaluate liver fat content using magnetic resonance imaging (MRI); hepatic fibrosis using MR elastography and vibration-controlled transient elastography; muscle composition and body fat distribution using water-fat separated whole body MRI; and cardiac function, structure, and tissue characteristics, using cardiovascular MRI.DiscussionWe expect that the study will uncover potential mechanisms of advanced hepatic fibrosis in NAFLD and T2DM and equip the clinician with better diagnostic tools for the care of T2DM patients with NAFLD.Trial registration: Clinicaltrials.gov, identifier NCT03864510. Registered 6 March 2019, https://clinicaltrials.gov/ct2/show/NCT03864510.

Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents.

This study explores the organization of medical physicists’, radiologists’, and radiographers’ professional work and the challenges they encounter ensuring quality and safe medical service within medical imaging. A practice theory perspective was used for data collection, which consisted of 14 open interviews, and data analysis. The concept of tension was used for the interpretation of findings. Three tensions are presented in the findings: 1) between diverse general and practical understandings about the activities in practice; 2) between material-economic conditions and activity in practice, and 3) between discursive-culture conditions and activity in practice. This study found that new technology, economical rationality, and the organisation of work processes lead to fewer face-to-face meetings between different professions. Therefore, medical imaging as dispersed practices misses opportunities for learning across practices, which can lead to patient safety risks. To ensure patient safety, new forms for learning across practices are needed.

BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.

METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score).

RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively.

CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.

In scoliosis, kypholordos and wedge properties of the vertebrae should be involved in determining how stress is distributed in the vertebral column. The impact is logically expected to be maximal at the apex.

Study Design

Retrospective study.

Objectives

To investigate parameters of axial vertebral deformation in patients with scoliosis compared to a control group, and to determine whether these parameters correlated with the severity of spine curvature, measured as the Cobb angle.

Summary of Background Data

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity. Many studies have investigated vertebral deformation, in terms of wedging and pedicle deformations, but few studies have investigated actual structural changes within vertebrae.

Methods

This study included 20 patients with AIS (Lenke 1–3, mean age: 15.6 years, range: 11–20). We compared preoperative low-dose computed tomography(CT) examinations of patients with AIS to those of a control group matched for age and sex. The control individuals had no spinal deformity, but they were admitted to the emergency department for trauma CTs. We measured the Cobb angles and the axial vertebral rotation (AVR), axial vertebral bodyasymmetry (AVBA), and frontal vertebral body rotation (FVBR) for the superior end, inferior end, and apical vertebrae, with in-house–developed software. Correlations between entities were investigated with the Pearson correlation test.

Results

The average Cobb angles were 49.3° and 1.3° for the scoliotic and control groups, respectively. The patient and control groups showed significant differences in the AVRs of all three vertebra levels (p < .01), the AVBAs of the superior end and apical vertebrae (p < .008), and the FVBR of the apical vertebra (p = .011). Correlations were only found between the AVBA and FVBR in the superior end vertebra (r = 0.728, p < .001) and in the apical vertebra (r = 0.713, p < .001).

Conclusions

Compared with controls, patients with scoliosis showed clear morphologic differences in the midaxial plane vertebrae. Differences in AVR, AVBA, and FVBR were most pronounced at the apical vertebra. The FVBR provided valuable additional information about the internal rotation and deformation of vertebrae.

Level of Evidence

Level III.