Liver Micro Flow - MRI

Magnetic Resonance Imaging (MRI)-Based Quantification of Perfusion and Microstructure

This study integrates and evaluates a series of novel MRI methods for quantifying blood perfusion and tissue microstructure. The proposed perfusion and microstructure measures may provide biomarkers for fibrosis, cirrhosis, portal hypertension, and response to treatment. The precision of these methods will be evaluated in 110 participants, including healthy volunteers, people with chronic liver disease (CLD), and people with liver fibrosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Diseases
• Intervention / Treatment: Device: Novel MRI Software; Other: Ensure Plus Nutrition Shake

Detailed Description

The overall goal of this project is to develop a next-generation, confounder-corrected Intravoxel incoherent motion (IVIM)-MRI method for quantification of tissue perfusion and microstructure, and to validate this method in patients with CLD. This protocol will address these unmet needs through the following specific aims:

Aim 1: Develop and optimize confounder-corrected IVIM to enable precise quantification over the entire liver.

Aim 2: Validate the technical and clinical performance of confounder-corrected IVIM in patients with CLD.

Aim 3: Demonstrate confounder-corrected IVIM as a marker of intrahepatic vascular resistance in patients with CLD, including those with and without portal hypertension.

Primary Objectives:

1. Repeatability of confounder-corrected IVIM [repeatability coefficient]
2. Reproducibility of IVIM across acquisition parameters [coefficient of reproducibility]
3. Ability to predict histological features (fibrosis stage) of CLD [area under the curve (AUC), optimal cutoffs, sensitivity, specificity]
4. Determine the response to a meal challenge in patients without and with portal hypertension [pre vs post meal change of IVIM parameters evaluated using mixed effects modeling]

• Study Type: Observational
• Enrollment (Estimated): 110

Contacts and Locations

• Study Contact: Name: Radiology Study; Phone Number: 608-282-8349; Email: Radstudy@uwhealth.org

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Healthy volunteers, patients with chronic liver disease across the Metabolic dysfunction-associated steatoic liver disease (MASLD) spectrum, including steatosis, steatohepatitis (MASH), fibrosis, cirrhosis, and portal hypertension.

Description

Inclusion Criteria (Healthy Volunteers):

• Age 7 years or older
• Willing and able to complete study procedures

Exclusion Criteria (Healthy Volunteers):

• Patients with contraindication to MRI (e.g. pacemaker, contraindicated metallic implants, claustrophobia, etc)
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety screening)
• Received ferumoxytol injection within previous one year (clinical or research)

• Patients requiring intravenous (IV) conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for the MRI will be allowed to participate as long as the following criteria are met:

  • The person has their own prescription for the medication.
  • The informed consent process is conducted prior to the self-administration of this medication
  • They come to the research visit with a driver

Inclusion Criteria (Participants with CLD):

• Age 7 years or older
• Willing and able to complete study procedures
• Clinical evidence of MASLD, MASH, cirrhosis or liver fibrosis

Exclusion Criteria (Participants with CLD):

• Patients with contraindication to MRI (e.g. pacemaker, contraindicated metallic implants, claustrophobia, etc)
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety screening)
• Received ferumoxytol injection within previous one year (clinical or research)

• Patients requiring intravenous (IV) conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for the MRI will be allowed to participate as long as the following criteria are met:

  • The person has their own prescription for the medication.
  • The informed consent process is conducted prior to the self-administration of this medication
  • They come to the research visit with a driver

Inclusion Criteria (Liver Fibrosis Spectrum):

• Age 7 years or older
• Willing and able to complete study procedures

• Known or suspected liver steatosis, steatohepatitis, fibrosis, cirrhosis, or portal hypertension, based on clinical imaging from the previous 6 months or histology over the previous 12 months.

  • At least N=50 will be selected based on having a clinically indicated liver biopsy
• If taking beta blocker medication, willing to temporarily discontinue the medication for three days prior to the research visit after providing informed consent and in consultation with their treating physician.

Exclusion Criteria (Liver Fibrosis Spectrum):

• Patients with contraindication to MRI (e.g. pacemaker, contraindicated metallic implants, claustrophobia, etc)
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety screening)
• Received ferumoxytol injection within previous one year (clinical or research)

• Patients requiring intravenous (IV) conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for the MRI will be allowed to participate as long as the following criteria are met:

  • The person has their own prescription for the medication.
  • The informed consent process is conducted prior to the self-administration of this medication
  • They come to the research visit with a driver

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers; Healthy participants without known liver disease undergoing a single research visit with non contrast MRI to support development, optimization, and evaluation of MRI based perfusion and microstructure measurements.	Device: Novel MRI Software; Each study visit will last approximately 2 hours; The visit will include approximately 1 hour of MR imaging; Participants will be asked to fast for 5 hours prior to the research visit; Other Names: non-contrast MRI
Participants with CLD; Participants with chronic liver disease undergoing a single research visit with non contrast MRI to evaluate repeatability and reproducibility of MRI based perfusion and microstructure measurements.	Device: Novel MRI Software; Each study visit will last approximately 2 hours; The visit will include approximately 1 hour of MR imaging; Participants will be asked to fast for 5 hours prior to the research visit; Other Names: non-contrast MRI
Participants with Liver Fibrosis; Participants with known or suspected liver fibrosis or portal hypertension undergoing a single research visit with non contrast MRI to evaluate imaging performance across the fibrosis spectrum. A subset of participants will also undergo a standardized meal challenge with pre and post meal imaging.	Device: Novel MRI Software; Each study visit will last approximately 2 hours; The visit will include approximately 1 hour of MR imaging; Participants will be asked to fast for 5 hours prior to the research visit; Other Names: non-contrast MRI; Other: Ensure Plus Nutrition Shake; A subset of participants (N=15 with portal hypertension and N=15 without portal hypertension) from the Liver Fibrosis Cohort will be imaged in the fasted state, then exit the scanner where they will be asked to drink two Ensure Plus Nutrition shake. After a 20-minute delay, each subject will re-enter the scanner for additional imaging.; Other Names: Meal challenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test-retest repeatability of IVIM parameters: Perfusion Fraction	Test-retest repeatability of IVIM parameters will be acquired during a single study visit, summarized using repeatability coefficients and Bland-Altman analysis.	data collected over one hour during one study visit
Test-retest repeatability of IVIM parameters: Blood Velocity Standard Deviation	Test-retest repeatability of IVIM parameters will be acquired during a single study visit, summarized using repeatability coefficients and Bland-Altman analysis.	data collected over one hour during one study visit
Test-retest repeatability of IVIM parameters: Diffusion Coefficient	Test-retest repeatability of IVIM parameters will be acquired during a single study visit, summarized using repeatability coefficients and Bland-Altman analysis.	data collected over one hour during one study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reproducibility of IVIM across acquisition parameters	Consistency of IVIM measurements across MRI acquisition parameters (relevant parameters include: respiratory motion mitigation approach (respiratory triggered vs free-breathing), and/or spatial resolution, and/or diffusion weighting values), summarized using coefficients of reproducibility and variation.	data collected over one hour during one study visit
Diagnostic performance for liver fibrosis: AUC	Diagnostic performance for liver fibrosis: Ability of IVIM parameters to differentiate histologic stages of liver fibrosis using ROC analysis.	data collected over one hour during one study visit
Diagnostic performance for liver fibrosis: Sensitivity (True Positive Rate)	Diagnostic performance for liver fibrosis: Ability of IVIM parameters to differentiate histologic stages (for example: distinguish stages 0-1 from stages 2-4) of liver fibrosis using ROC analysis.	data collected over one hour during one study visit
Diagnostic performance for liver fibrosis: Specificity (True Negative Rate)	Diagnostic performance for liver fibrosis: Ability of IVIM parameters to differentiate histologic stages (for example: distinguish stages 0-1 from stages 2-4) of liver fibrosis using ROC analysis.	data collected over one hour during one study visit
Response to Meal Challenge in Participants with and without Portal Hypertension	Change in IVIM derived perfusion parameters before and after a standardized meal challenge in participants with and without portal hypertension, evaluated using mixed effects modeling.	data collected over one hour during one study visit (pre and post meal imaging)
Image Quality	Radiologist rated image quality using a 5 point Likert scale assessing motion, distortion, apparent SNR, and overall quality. Scored from 1-5 with higher scores meaning better quality.	data collected over one hour during one study visit

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
• Investigators: Principal Investigator: Diego Hernando, PhD, UW School of Medicine and Public Health

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: MRI; microstructure; tissue perfusion; IVIM
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 2026-0346; R01EB037002 (U.S. NIH Grant/Contract); Protocol Version 4/14/26 (Other Identifier: UW Madison); SMPH | Radiology (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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.: Yes