Dataset Information

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

ABSTRACT: BACKGROUND:The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies. OBJECTIVE:The primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories. METHODS:RADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit. RESULTS:This trial is currently open for recruitment. The anticipated completion date for the study is December 2020. CONCLUSIONS:This randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies. TRIAL REGISTRATION:ClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/19189.

SUBMITTER: Tonev D

PROVIDER: S-EPMC7652684 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

Tonev Dimitar D Shumbayawonda Elizabeth E Tetlow Louise Ann LA Herdman Laura L French Marika M Rymell Soubera S Thomaides-Brears Helena H Caseiro-Alves Filipe F Castelo-Branco Miguel M Ferreira Carlos C Coenraad Minneke M Lamb Hildo H Beer Meinrad M Kelly Matt M Banerjee Rajarshi R Dollinger Matthias M

JMIR research protocols 20201026 10

<h4>Background</h4>The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive ...[more]

PMID: 33104014

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Project description:Background & aimsPatients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) often require histologic assessment via liver biopsy. Magnetic resonance imaging (MRI)-based methods for measuring liver triglycerides based on proton density fat fraction (PDFF) are increasingly used as a noninvasive tool to identify patients with hepatic steatosis and to assess for change in liver fat over time. We aimed to determine whether MRI-PDFF accurately reflects a variety of liver histology features in patients with NAFLD or NASH.MethodsWe performed a retrospective analysis of pooled data from 3 phase 2a trials of pharmacotherapies for NAFLD or NASH. We collected baseline clinical, laboratory, and histopathology data on all subjects who had undergone MRI analysis in 1 of the trials. We assessed the relationship between liver PDFF values and liver histologic findings using correlation and area under the receiver operating characteristic (AUROC) analyses. As an ancillary analysis, we also simulated a clinical trial selection process and calculated subject exclusion rates and differences in population characteristics caused by PDFF inclusion thresholds of 6% to 15%.ResultsIn 370 subjects, the mean baseline PDFF was 17.4% ± 8.6%. Baseline PDFF values correlated with several histopathology parameters, including steatosis grade (r = 0.78; P < .001), NAFLD activity score (NAS, r = 0.54; P < .001), and fibrosis stage (r = -0.59; P < .001). However, PDFF did not accurately identify patients with NAS ≥ 4 (AUROC = 0.72) or fibrosis stage ≥3 (AUROC = 0.66). In a theoretical trial of these subjects, exclusion rates increased as PDFF minimum threshold level increased. There were no significant differences in cohort demographics when PDFF thresholds ranging from 6% to 15% were used, and differences in laboratory and histopathology data were small.ConclusionsIn an analysis of patients with NAFLD or NASH, we determined that although The MRI-PDFF correlated with steatosis grade and NAS, and inversely with fibrosis stage, it was suboptimal in identification of patients with NAS >4 or advanced fibrosis. Although MRI-PDFF is an important imaging biomarker for continued evaluation of this patient population, liver biopsy analysis is still necessary.

Project description:ObjectiveThe aim of this study was to characterize response to photodynamic therapy (PDT) in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome.MethodsCT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of BALB/c mice. Therapy consisted of intravenous injection of the photosensitizer Bremachlorin, followed by 10 min laser illumination (200 mW/cm2) of the tumor 6 h post injection. MRI at 7 T was performed at baseline, directly after PDT, as well as at 24 h, and 72 h. Tumor relaxation time constants (T1 and T2) and apparent diffusion coefficient (ADC) were quantified at each time point. Additionally, Gd-DOTA dynamic contrast-enhanced (DCE) MRI was performed to estimate transfer constants (Ktrans) and volume fractions of the extravascular extracellular space (ve) using standard Tofts-Kermode tracer kinetic modeling. At the end of the experiment, tumor viability was characterized by histology using NADH-diaphorase staining.ResultsThe therapy induced extensive cell death in the tumor and resulted in significant reduction in tumor growth, as compared to untreated controls. Tumor T1 and T2 relaxation times remained unchanged up to 24 h, but decreased at 72 h after treatment. Tumor ADC values significantly increased at 24 h and 72 h. DCE-MRI derived tracer kinetic parameters displayed an early response to the treatment. Directly after PDT complete vascular shutdown was observed in large parts of the tumors and reduced uptake (decreased Ktrans) in remaining tumor tissue. At 24 h, contrast uptake in most tumors was essentially absent. Out of 5 animals that were monitored for 2 weeks after treatment, 3 had tumor recurrence, in locations that showed strong contrast uptake at 72 h.ConclusionDCE-MRI is an effective tool for visualization of vascular effects directly after PDT. Endogenous contrast parameters T1, T2, and ADC, measured at 24 to 72 h after PDT, are also potential biomarkers for evaluation of therapy outcome.

Project description:OBJECTIVES:To investigate the use of MR elastography (MRE)-derived mechanical properties (shear stiffness (|G*|) and loss modulus (G?)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. METHODS:Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G?) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. RESULTS:The combination of FF, |G*|, and G? predicted NAS?>?1 with excellent accuracy in both training and testing sets (AUROC?>?0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between "not-NASH" and "definite-NASH." "Borderline-NASH" prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. CONCLUSION:This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. KEY POINTS:• MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC?>?0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80-92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

Project description:BackgroundRadiologists currently subjectively examine multi-parametric magnetic resonance imaging (MP-MRI) to determine prostate tumor aggressiveness using the Prostate Imaging Reporting and Data System scoring system (PI-RADS). Recent studies showed that modified signal to clutter ratio (SCR), tumor volume, and eccentricity (elongation or roundness) of prostate tumors correlated with Gleason score (GS). No previous studies have combined the prostate tumor's shape, SCR, tumor volume, in order to predict potential tumor aggressiveness and GS.MethodsMP-MRI (T1, T2, diffusion, dynamic contrast-enhanced images) were obtained, resized, translated, and stitched to form spatially registered multi-parametric cubes. Multi-parametric signatures that characterize prostate tumors were inserted into a target detection algorithm [adaptive cosine estimator (ACE)]. Pixel-based blobbing, and labeling were applied to the threshold ACE images. Eccentricity calculation used moments of inertia from the blobs. Tumor volume was computed by counting pixels within multi parametric MRI blobs and tumor outlines based on pathologist assessment of whole mount histology. Pathology assessment of GS was performed on whole mount prostatectomy. The covariance matrix and mean of normal tissue background was computed from normal prostate. Using signatures and normal tissue statistics, the z-score, noise corrected SCR [principal component (PC), modified regularization] from each patient was computed. Eccentricity, tumor volume, and SCR were fitted to GS. Analysis of variance assesses the relationship among the variables.ResultsA multivariate analysis generated correlation coefficient (0.60 to 0.784) and P value (0.00741 to <0.0001) from fitting two sets of independent variates, namely, tumor eccentricity (the eccentricity for the largest blob, weighted average for the eccentricity) and SCR (removing 3 PCs, removing 4 PCs, modified regularization, and z-score) to GS. The eccentricity t-statistic exceeded the SCR t-statistic. The three-variable fit to GS using tumor volume (histology, MRI) yielded correlation coefficients ranging from 0.724 to 0.819 (P value <<0.05). Tumor volumes generated from histology yielded higher correlation coefficients than MRI volumes. Adding volume to eccentricity and SCR adds little improvement for fitting GS due to higher correlation coefficients among independent variables and little additional, independent information.ConclusionsCombining prostate tumors eccentricity with SCR relatively highly correlates with GS.

Project description:ObjectiveTo investigate the diagnostic performance of quantitative ultrasound (US) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard.Materials and methodsIn this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. The participants underwent US examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, the attenuation coefficient (AC) based on tissue attenuation imaging (TAI) (AC-TAI) and scatter-distribution coefficient (SC) based on tissue scatter-distribution imaging (TSI) (SC-TSI) were measured. The correlations between the quantitative US parameters (AC and SC) and MRI-PDFF were evaluated using Pearson correlation coefficients. The diagnostic performance of AC-TAI and SC-TSI for detecting hepatic fat contents of ≥ 5% (MRI-PDFF ≥ 5%) and ≥ 10% (MRI-PDFF ≥ 10%) were assessed using receiver operating characteristic (ROC) analysis. The significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis.ResultsThe participants were classified based on MRI-PDFF: < 5% (n = 38), 5-10% (n = 23), and ≥ 10% (n = 59). AC-TAI and SC-TSI were significantly correlated with MRI-PDFF (r = 0.659 and 0.727, p < 0.001 for both). For detecting hepatic fat contents of ≥ 5% and ≥ 10%, the areas under the ROC curves of AC-TAI were 0.861 (95% confidence interval [CI]: 0.786-0.918) and 0.835 (95% CI: 0.757-0.897), and those of SC-TSI were 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972), respectively. Multivariable linear regression analysis showed that MRI-PDFF was an independent determinant of AC-TAI and SC-TSI.ConclusionAC-TAI and SC-TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.

Dataset Information

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

Publications

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial.

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