Clinical Application of Annual Liver Multiscan and MRCP+ in Primary Sclerosing Cholangitis (CATCH-IT)

Clinical Application of Annual Liver Multiscan and MRCP+ in Primary Sclerosing Cholangitis: the CATCH-IT Study

Primary sclerosing cholangitis (PSC) is a chronic progressive biliary disease that affects approximately 1200 patients in the Netherlands and around 80,000 in the Western world. It is often accompanied by ulcerative colitis (UC) or Crohn's disease affecting the large bowel. The cause of PSC is unknown, there is no medical therapy available that has proven to halt disease progression and the median time until death or liver transplantation is 13-21 years. Diagnosis is made by magnetic resonance cholangiography (MRC), or in the case of so called small duct disease by liver biopsy. Due to the heterogeneous disease course and the relatively low clinical event rate of 5% per year it is difficult to predict prognosis of individual patients or to recommend any surveillance strategy for malignancies. Also, the lack of surrogate endpoints impedes performing clinical research. Recently, two new post-processing tools have been developed to characterize and quantify abnormalities in the biliary tree as well as excretory function captured by MRC. These tools called MRCP+ (quantitative magnetic resonance cholangiopancreatography +) and LiverMultiscan (LMS) hold the prospect of adequately depicting and quantifying lesions of the biliary tree as well as capturing functional derailment. However, several features must be tested before the utility of this tools in clinical patient care can be concluded. Therefore, the aim of this study is to investigate the utility of these novel techniques in monitoring disease activity by performing consecutive annual MRI's.

PSC patients that undergo annual, standard care, MRI of the liver and MRCP will undergo additional Liver Multiscan sequences, taking approximately 15 minutes. After the MRI is performed, post-processing analysis named MRCP+ and LiverMultiscan will be performed without patient involvement.

Additional Liver Multiscan sequences will be performed after the MRI liver with MRCP is performed, taking approximately 15 minutes.

Post processing tool (Software) for determining the corrected T1 time after the additional LMS sequences at baseline are performed. This cT1 reflects the activity of inflammation/fibrosis of the liver. Patient involvement is not necessary during this procedure.

Post processing tool (Software) for quantifying MRCP images after the MRCP from follow up is performed. Patient involvement is not necessary during this procedure.

The delta of cT1 (in ms), measured by LiverMultiscan, which will be assessed by performing paired t-tests.

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

Mean, median and range of cT1 and MRCP+ metrics in clinically and biochemically stable patients with PSC during the period of 1 year to establish general statistics as these are unknown at current writing

Variance of the delta in cT1 and MRCP+ metrics from baseline to year 1 in clinically and biochemically stable patients

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

Difference in mean of cT1 values in patients who needed ERCP with treatment of dominant stricture(s) in the year following LMS measurement versus those who did not need an intervention

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

Variance of the delta of cT1 and MRCP+ metrics in sequential scans in biochemically and/or clinically deteriorating patients.

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

1st MRI = baseline = week 0; 2nd MRI = year 1 = week 52; 3rd MRI = year 2 = week 104; 4th MRI = year 3 = week 156; 5th MRI = year 4 = week 208; 6th MRI = year 5 = week 260.

Inclusion Criteria: Established PSC diagnosis according to the IPSCSG definitions Age ≥ 18 Able to give informed consent Exclusion Criteria: Post LTx Known allergy for MRI contrast agents, implants non-compatible with MRI or extreme claustrophobia causing discontinuation of MRI studies.

After publication, the following documentation can be requested by qualified research groups: - Study protocol, statistical analysis plan and the clinical study report can be provided if a proper request is submitted. IPD will contain decoded and only essential data for the objective of this study. Data that will be available for sharing purposes will only include decoded demographic data. Furthermore, MRCP+ data that underlies the results in the publication will be available for sharing, e.g. MRCP+ metrics

Data sharing can be requested by qualified research groups. Requests will be evaluated by the following method: The request is supposed to contain a clear objective and methodology. E.g., it must contain the objective to explore or validate the value of MRCP+ and LMS techniques. Furthermore, the study proposal could, for example, be a systematic review or meta-analysis. The request will be reviewed by a dedicated research team of the CATCH-IT-study. This research team contains the PI, PhD student, involved gastro-enterologist and radiologist and representative of Perspectum Ltd. If the request seems valid and the credibility of the requesting party is validated, data sharing agreement will be developed with the local research support team. To submit a request, contact t.e.middelburg@amsterdamumc.nl

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