Repeatability and Reproducibility of Multiparametric MRI

Repeatability and Reproducibility of Multiparametric MRI (LiverMultiScan)

This study aims to prospectively assess the repeatability and reproducibility of iron-corrected T1 (cT1), T2*, and hepatic proton density fat fraction (PDFF) quantification with multiparametric MRI using the LiverMultiScan™ (LMS, Perspectum Diagnostics, Oxford, UK) protocol across different field strengths, scanner manufacturers and models.

Study Overview

• Status: Recruiting
• Conditions: Liver Diseases; Cirrhosis; Primary Sclerosing Cholangitis; Autoimmune Hepatitis; Hemochromatosis; Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Steatohepatitis; Primary Biliary Cirrhosis; Viral Hepatitis
• Intervention / Treatment: Device: LiverMultiScan

Detailed Description

As the burden of liver disease reaches epidemic levels, there is a high unmet medical need to develop robust, accurate and reproducible non-invasive methods to quantify liver tissue characteristics for use in clinical development and ultimately in clinical practice. Repeatability and reproducibility validation studies are important in evaluating metrics, such that any changes can be confidently attributed to disease progression or regression, rather than inter-examination variability in the instrument.

Magnetic resonance (MR) techniques offer an attractive non-invasive option for liver assessment. Multiparametric MRI is a safe and non-invasive method for quantification of liver tissue characteristics. Images for quantification of hepatic fat from proton density fat fraction (PDFF) maps, T2*, and iron-corrected T1 (cT1) can be rapidly obtained during abdominal breath-hold acquisitions without the need for contrast agents or additional external hardware. Iron correction of T1 is necessary to address the confounding effects of excess iron, which is common in chronic liver disease. LiverMultiScan™ (LMS, Perspectum Diagnostics, Oxford, UK) is a software application that can be used with supported MR-systems to correct T1 for the effects of excess iron, and thus, to calculate cT1 from T1 and T2* maps, and standardise to a 3T field strength.

This method has been shown to have high diagnostic accuracy for the assessment of liver fibrosis compared to histology, predict clinical outcomes in patients with mixed liver disease aetiology, stratify patients with non-alcoholic steatohepatitis (NASH) and cirrhosis, reliably exclude clinically significant liver disease and is cost-effective in diagnosing NAFLD.

In addition to demonstrating accuracy, imaging biomarker validation requires precision and repeatability (US Department of Health and Human Services, 2015). From a clinical perspective, it is essential to ensure that there is good inter-examination repeatability, so that any changes seen can be correctly attributed to disease progression or regression, rather than inter-examination variability. This is tested by examining the closeness of repeated measurements made in different MR examinations (with both subject and coil repositioning) over a time frame in which physiologic conditions are assumed constant.

This study aims to systematically test the repeatability and reproducibility of each multiparametric MRI measurement, cT1, T2* and PDFF, corresponding to hepatic fibro-inflammation, iron and fat respectively, across scanner field strength, manufacturer and model in human participants and phantoms.

• Study Type: Observational
• Enrollment (Anticipated): 61

Contacts and Locations

• Study Contact: Name: Soubera Rymell, BSc; Phone Number: +441865655343; Email: soubera.rymell@perspectum.com
• Study Contact Backup: Name: Velicia Bachtiar, DPhil; Phone Number: +441865655343; Email: velicia.bachtiar@perspectum-diagnostics.com

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Active, not recruiting
    • Leiden University Medical Centre
• United Kingdom
  • Southampton, United Kingdom
    • Active, not recruiting
    • Southampton General Hospital
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Completed
      • Addenbrookes Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR)
      • Contact: Kathryn Lacey; Phone Number: +441865220245; Email: kathryn.lacey@cardiov.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants are those with mixed liver disease aetiology and those without any history of liver disease in order to represent a wide range of values of hepatic fat, iron, and fibro-inflammatory status.

Description

Inclusion Criteria:

• Any person over 18 years of age.
• Participant is willing and able to give informed consent.

Exclusion Criteria:

• The participant may not enter the study if they have any contraindication to magnetic resonance imaging (inc pregnancy, extensive tattoos, pacemaker, shrapnel injury, severe claustrophobia).
• Any other cause, including a significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study or affect the participant's ability to participate in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Liver condition; Participants who have a history of of liver disease	Device: LiverMultiScan; Up to 6 separate 5-10 minute abdominal MRI scans. Each scan requires a short breath hold.; Other Names: Multiparametric Magnetic Resonance Imaging (mpMRI)
Healthy volunteers; Participants who have do not have a diagnosed liver condition and are in general good health	Device: LiverMultiScan; Up to 6 separate 5-10 minute abdominal MRI scans. Each scan requires a short breath hold.; Other Names: Multiparametric Magnetic Resonance Imaging (mpMRI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repeatability	Comparison of multi-parametric MRI measures (MRI-PDFF, T2* and iron-corrected T1 (cT1)) from repeated acquisitions of the same participant on the same scanner.	2 years
Reproducibility	Comparison of multi-parametric MRI measures (MRI-PDFF, T2* and iron-corrected T1 (cT1)) from repeated acquisitions of the same participant on different scanners (1.5T and 3.0T).	2 years

Collaborators and Investigators

• Sponsor: Perspectum
• Investigators: Principal Investigator: Rajarshi Banerjee, BM BCh MS DPhil, Perspectum Diagnostics

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2017
• Primary Completion (Anticipated): June 17, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 1, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Multiparametric MRI; Reproducibility; Repeatability; LiverMultiScan; Liver MRI
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; RNA Virus Infections; Virus Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Genetic Diseases, Inborn; Hepatitis, Viral, Human; Iron Metabolism Disorders; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Metabolism, Inborn Errors; Biliary Tract Diseases; Bile Duct Diseases; Metal Metabolism, Inborn Errors; Iron Overload; Cholestasis, Intrahepatic; Cholestasis; Liver Diseases; Fibrosis; Hepatitis; Hepatitis A; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Cholangitis; Cholangitis, Sclerosing; Hepatitis, Autoimmune; Hemochromatosis; Hemosiderosis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: LMSRR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No