Repeatability and Reproducibility of Multiparametric MRI

• ClinicalTrials.gov Identifier: NCT03743272
• Recruitment Status: Unknown
• First Posted: November 16, 2018
• Last Update Posted: August 3, 2021
• Sponsor: Perspectum
• Information provided by (Responsible Party): Perspectum

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Liver Diseases; Primary Biliary Cirrhosis; Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Steatohepatitis; Cirrhosis; Hemochromatosis; Viral Hepatitis; Autoimmune Hepatitis; Primary Sclerosing Cholangitis	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 Design

• Study Type: Observational
• Estimated Enrollment: 61 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Repeatability and Reproducibility of Multiparametric MRI (LiverMultiScan)
• Actual Study Start Date: June 3, 2017
• Estimated Primary Completion Date: June 17, 2022
• Estimated Study Completion Date: November 1, 2022

Groups and Cohorts

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 Name: 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 Name: Multiparametric Magnetic Resonance Imaging (mpMRI)

Outcome Measures

Primary Outcome Measures :

1. Repeatability [ Time Frame: 2 years ]
   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. Reproducibility [ Time Frame: 2 years ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• 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.

Criteria

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.

Contacts and Locations

Contacts

Contact: Soubera Rymell, BSc; +441865655343; soubera.rymell@perspectum.com

Contact: Velicia Bachtiar, DPhil; +441865655343; velicia.bachtiar@perspectum-diagnostics.com

Locations

Netherlands

Leiden University Medical Centre; Active, not recruiting

Leiden, Netherlands

United Kingdom

Addenbrookes Hospital; Completed

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR); Recruiting

Oxford, Oxfordshire, United Kingdom, OX3 9DU

Contact: Kathryn Lacey +441865220245 kathryn.lacey@cardiov.ox.ac.uk

Southampton General Hospital; Active, not recruiting

Southampton, United Kingdom

Sponsors and Collaborators

Perspectum

Investigators

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

More Information

• Responsible Party: Perspectum
• ClinicalTrials.gov Identifier: NCT03743272
• Other Study ID Numbers: LMSRR
• First Posted: November 16, 2018
• Last Update Posted: August 3, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Perspectum:

Multiparametric MRI; LiverMultiScan; Repeatability; Reproducibility; Liver MRI

Additional relevant MeSH terms:

Hepatitis A; Hepatitis; Liver Cirrhosis; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Cholangitis; Cholangitis, Sclerosing; Liver Cirrhosis, Biliary; Hepatitis, Autoimmune; Hemochromatosis; Hemosiderosis; Fibrosis; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Pathologic Processes; Bile Duct Diseases; Biliary Tract Diseases; Cholestasis, Intrahepatic; Cholestasis; Hepatitis, Chronic; Autoimmune Diseases; Immune System Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors