Liver Diseases
Conditions
Keywords
MRI, IVIM, tissue perfusion, microstructure
Brief summary
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.
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 \[pre vs post meal change of IVIM parameters evaluated using mixed effects modeling\]
Interventions
DEVICENovel 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
OTHEREnsure 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.
Sponsors
University of Wisconsin, Madison
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test-retest repeatability of IVIM parameters: Diffusion Coefficient | data collected over one hour during one study visit | Test-retest repeatability of IVIM parameters will be acquired during a single study visit, summarized using repeatability coefficients and Bland-Altman analysis. |
| Test-retest repeatability of IVIM parameters: Perfusion Fraction | data collected over one hour during one study visit | Test-retest repeatability of IVIM parameters will be acquired during a single study visit, summarized using repeatability coefficients and Bland-Altman analysis. |
| Test-retest repeatability of IVIM parameters: Blood Velocity Standard Deviation | data collected over one hour during one study visit | Test-retest repeatability of IVIM parameters will be acquired during a single study visit, summarized using repeatability coefficients and Bland-Altman analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image Quality | data collected over one hour during one study visit | 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. |
| Reproducibility of IVIM across acquisition parameters | data collected over one hour during one study visit | 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. |
| Diagnostic performance for liver fibrosis: Sensitivity (True Positive Rate) | data collected over one hour during one study visit | 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. |
| Diagnostic performance for liver fibrosis: AUC | data collected over one hour during one study visit | Diagnostic performance for liver fibrosis: Ability of IVIM parameters to differentiate histologic stages of liver fibrosis using ROC analysis. |
| Diagnostic performance for liver fibrosis: Specificity (True Negative Rate) | data collected over one hour during one study visit | 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. |
| Response to Meal Challenge in Participants with and without Portal Hypertension | data collected over one hour during one study visit (pre and post meal imaging) | 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. |
Countries
United States
Contacts
CONTACTRadiology Study
PRINCIPAL_INVESTIGATORDiego Hernando, PhD
UW School of Medicine and Public Health
Outcome results
None listed