Detection of Liver Fibrosis With Magnetic Resonance Imaging (MRI)

Sponsor
Bachir Taouli (Other)
Overall Status
Completed
CT.gov ID
NCT01600105
Collaborator
(none)
276
1
1
82
3.4

Study Details

Study Description

Brief Summary

Patients with chronic liver disease are at high risk of developing liver scarring (fibrosis), with ultimate risks of cirrhosis and liver cancer that may require liver transplant. The investigators would like to develop non invasive advanced Magnetic Resonance Imaging (MRI) techniques (MR diffusion, perfusion and elastography) to assess the degree of liver damage in patients with chronic liver disease. These techniques combined could reach high diagnostic performance for detection of liver fibrosis; and could decrease the number of liver biopsies, which have risks and sample only a small portion of the liver.

Condition or Disease Intervention/Treatment Phase
  • Drug: Perfusion MRI
Phase 4

Detailed Description

Patients with chronic hepatitis have increased risks of liver damage, including fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma and end-stage liver disease requiring liver transplantation. These diseases are/will be the source of enormous health care costs and morbidity/mortality in the US.

Most hepatologists still rely on liver biopsy findings in patients newly diagnosed with chronic hepatitis, which enables the assessment of liver damage (fibrosis and inflammation). Liver biopsy has limitations, including cost, invasiveness, poor patient acceptance, limited sampling, inter-observer variability and is difficult to repeat.

Non invasive tests to capture the extent of liver damage at a larger scale are urgently needed. These will gain more acceptance among patients and hepatologists.

In this proposal, the investigators would like to test and validate non invasive MRI methods based on advanced MR diffusion, perfusion and elastography techniques for the detection of fibrosis and cirrhosis in patients with chronic hepatitis. In order to improve the diagnostic performance of MRI, the investigators would like to build and validate a predictive model based on advanced functional MRI metrics (diffusion, perfusion and elastography). If validated, this novel non invasive algorithm will not only decreases the number of liver biopsies, but also enable earlier diagnosis of liver fibrosis when antiviral treatment is more effective, and enable a comprehensive evaluation of the liver (to assess for cirrhosis, portal hypertension and hepatocellular cancer).

This could significantly reduce the cost of care, could become a useful tool for testing new antifibrogenic and antiviral drugs in chronic viral hepatitis, and could be used to follow patients for detection of progression to cirrhosis.

Study Design

Study Type:
Interventional
Actual Enrollment :
276 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Prospective Detection of Liver Fibrosis With MRI Compared to Fibroscan and Blood Tests
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Jul 31, 2017
Actual Study Completion Date :
Jul 31, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Perfusion MRI

chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months.

Drug: Perfusion MRI
1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
Other Names:
  • Dynamic contrast-enhanced MRI
  • Perfusion MRI (adofosveset trisodium, Ablavar, Lantheus)
  • Outcome Measures

    Primary Outcome Measures

    1. PV Flow [Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)]

      Sub-Study I Portal Venous Flow - forward flow during systole and early diastole, and flow reversal after atrial contraction.The average PV area was extracted, and PV flow was computed as the multiplication of area and velocity.

    2. PV Velocity [Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)]

      Sub-Study I Portal Venous Flow Velocity - The mean velocity of the region of interest (ROI) was extracted for each one of the 25 phase images, and the time average was computed.

    3. LS-MRE for Sub-Study I [Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)]

      Sub-Study I Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images.

    4. True Diffusion Parameter (D) [Fasting State Multiparametric MRI Scan (an average of 60 min) Scan]

      Sub-Study II True Diffusion Parameter - D- describes water diffusion in tissue independently from the effects of capillary perfusion; it is obtained from bi-exponential fitting of MRI diffusion signal acquired over a range of high and low diffusion-weighting factors (b-values) Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis

    5. LS-MRE Fibrosis State for Sub Study II [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study II Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images. Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis

    6. LS-TE [Fasting transient elastography, average duration 10 min]

      Sub-Study II Liver Stiffness with transient elastography (TE) (LS-TE) - a non-invasive modality of liver fibrosis detection: a shear wave is sent into the liver through a small transducer attached to an ultrasound probe, and the velocity of the wave is measured as it passes through the liver; shear wave velocity is then converted to stiffness, measured in kilopascals (kPa) Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis

    7. MTT [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study II Mean Transit Time (MTT) - Liver Mean Transit Time of Contrast Agent through the tissue of interest from Dynamic Contrast Enhanced MRI Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis

    Secondary Outcome Measures

    1. Liver Upslope From DCE-MRI [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Liver Upslope of MRI signal is defined as peak concentration to the time to reach peak concentration of gadolinium contrast agent in the liver tissue of interest, derived from dynamic contrast-enhanced MRI (DCE-MRI. Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg

    2. Liver Time to Peak (TTP) for PH [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Liver Time to Peak (TTP) is defined as the time in seconds to reach peak concentration of gadolinium contrast agent in the liver tissue of interest, derived from dynamic contrast-enhanced MRI (DCE-MRI) Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) ≥5 mmHg Clinically Significant Portal Hypertension is defined as an HVPG ≥10 mmHg

    3. LS-MRE Portal Hypertension for Sub Study III [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images. Portal Hypertension is defined as an HVPG ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg

    4. Spleen Volume [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg

    5. Spleen Caudocranial Diameter [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg

    6. PH Imaging Score [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Portal Hypertension imaging composite score (based on the presence of varices, spleen size, presence of ascites). The imaging score is based on the number of variceal sites (0: absence of varices, 1: one variceal site, 2: two variceal sites, and 3: 3 or more variceal sites), volume of ascites (0: no ascites, 1: minimal perihepatic and perisplenic fluid, 2: intraperitoneal fluid without marked abdominal wall distension, and 3: fluid causing marked abdominal wall distension), and maximum craniocaudal diameter of the spleen (0: size less than 13 cm, 1: size between 13 and 15 cm, 2: size between 15 and 20 cm, and 3: size greater than 20 cm). Score from 0 to 9, with higher score indicating worse disease. Portal Hypertension is defined as an HVPG ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg

    7. LSLU [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub-Study III Liver Stiffness to Liver Upslope ratio (LSLU) Portal Hypertension is defined as an HVPG ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg

    8. Liver DV [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub Study III Liver Distribution Volume (DV) is the distribution volume of contrast agent in the tissue of interest defined as a percentage ratio of gadolinium material volume to the volume of the liver tissue of interest, as derived from DCE-MRI; in the case of a contrast agent with extracellular distribution, DV measures the intravascular and extravascular-extracellular volume. Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg

    9. Spleen TTP [Fasting State Multiparametric MRI Scan (an average of 60 min)]

      Sub Study III Spleen Time To Peak (TTP) - time to reach peak gadolinium concentration in spleen tissue of interest, derived from DCE-MRI. Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Chronic liver disease (including viral hepatitis, alcoholic hepatitis, non alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, etc..)

    • 18 years of age and older

    • Liver biopsy (percutaneous or transjugular or surgical) performed within 6 months, as part of routine clinical care.

    • Liver transplant or liver resection performed within 6 months, as part of routine clinical care.

    • Patient is able to give informed consent for this study and agrees to provide a blood sample

    Control group

    • Patients without history of liver disease and healthy volunteers

    • 18 years of age and older

    • Subject is able to give informed consent for this study and agrees to provide a blood sample

    Exclusion Criteria:
    • Age less than 18 years

    • Unable or unwilling to give informed consent

    • Contra-indications to MRI

    • Electrical implants such as cardiac pacemakers or perfusion pumps

    • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants

    • Ferromagnetic objects such as jewelry or metal clips in clothing

    • Pregnant subjects

    • Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Icahn School of Medicine at Mount Sinai New York New York United States 10029

    Sponsors and Collaborators

    • Bachir Taouli

    Investigators

    • Principal Investigator: Bachir Taouli, MD, Icahn School of Medicine at Mount Sinai

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Bachir Taouli, Associate Professor, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT01600105
    Other Study ID Numbers:
    • GCO 09-1187
    First Posted:
    May 16, 2012
    Last Update Posted:
    Feb 7, 2020
    Last Verified:
    Jan 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bachir Taouli, Associate Professor, Icahn School of Medicine at Mount Sinai
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Recruitment began in May 2010, with enrollment from October 2010 through February 2017. Patients were recruited from the Division of Liver Diseases or from the Surgical Oncology Clinic at Mount Sinai.
    Pre-assignment Detail
    Arm/Group Title Chronic Liver Disease Patients Healthy Volunteers
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Sub Study I: Patients were enrolled in the study if they had a liver biopsy performed within 3 months of the MRI study or were diagnosed with liver cirrhosis based on imaging findings. Sub Study II: Patients with mixed etiology of liver fibrosis proven by biopsy, and/or liver cirrhosis. Sub study III: Patients with chronic liver disease who underwent invasive hepatic vein pressure gradient (HVPG) measurement Healthy Volunteer for Sub study I
    Period Title: Total Participants
    STARTED 255 21
    COMPLETED 214 11
    NOT COMPLETED 41 10
    Period Title: Total Participants
    STARTED 19 21
    COMPLETED 19 11
    NOT COMPLETED 0 10
    Period Title: Total Participants
    STARTED 65 0
    COMPLETED 60 0
    NOT COMPLETED 5 0
    Period Title: Total Participants
    STARTED 39 0
    COMPLETED 34 0
    NOT COMPLETED 5 0
    Period Title: Total Participants
    STARTED 41 8
    COMPLETED 41 8
    NOT COMPLETED 0 0
    Period Title: Total Participants
    STARTED 52 0
    COMPLETED 50 0
    NOT COMPLETED 2 0

    Baseline Characteristics

    Arm/Group Title Perfusion MRI Healthy Volunteers Total
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents. Healthy Volunteers in Sub study I only Total of all reporting groups
    Overall Participants 214 11 225
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    53.8
    30.6
    51.8
    Age, Customized (years) [Mean (Full Range) ]
    Sub Study I Chronic Hepatitis C patients
    55.8
    30.6
    46.5
    Age, Customized (years) [Mean (Full Range) ]
    Sub Study II
    55
    55
    Age, Customized (years) [Mean (Full Range) ]
    Sub Study III
    53
    53
    Age, Customized (years) [Mean (Full Range) ]
    Sub Study IV
    53
    29
    48
    Age, Customized (years) [Mean (Full Range) ]
    Sub Study V
    57
    57
    Sex: Female, Male (Count of Participants)
    Female
    83
    38.8%
    5
    45.5%
    88
    39.1%
    Male
    131
    61.2%
    6
    54.5%
    137
    60.9%
    Sex: Female, Male (Count of Participants)
    Female
    2
    0.9%
    5
    45.5%
    7
    3.1%
    Male
    17
    7.9%
    6
    54.5%
    23
    10.2%
    Sex: Female, Male (Count of Participants)
    Female
    20
    9.3%
    20
    181.8%
    Male
    40
    18.7%
    40
    363.6%
    Sex: Female, Male (Count of Participants)
    Female
    18
    8.4%
    18
    163.6%
    Male
    16
    7.5%
    16
    145.5%
    Sex: Female, Male (Count of Participants)
    Female
    18
    8.4%
    5
    45.5%
    23
    10.2%
    Male
    23
    10.7%
    3
    27.3%
    26
    11.6%
    Sex: Female, Male (Count of Participants)
    Female
    20
    9.3%
    20
    181.8%
    Male
    32
    15%
    32
    290.9%
    Race/Ethnicity, Customized (Count of Participants)
    White
    105
    49.1%
    3
    27.3%
    108
    48%
    Asian
    31
    14.5%
    1
    9.1%
    32
    14.2%
    Black or African American
    20
    9.3%
    5
    45.5%
    25
    11.1%
    Hispanic
    38
    17.8%
    2
    18.2%
    40
    17.8%
    Unknown
    20
    9.3%
    0
    0%
    20
    8.9%

    Outcome Measures

    1. Primary Outcome
    Title PV Flow
    Description Sub-Study I Portal Venous Flow - forward flow during systole and early diastole, and flow reversal after atrial contraction.The average PV area was extracted, and PV flow was computed as the multiplication of area and velocity.
    Time Frame Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Chronic Hep C Patients Healthy Volunteers
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents. No Hep C
    Measure Participants 19 11
    Fasting
    16.0
    (6.1)
    15.5
    (4.2)
    Postprandial
    23.2
    (8.5)
    27.1
    (10.2)
    2. Primary Outcome
    Title PV Velocity
    Description Sub-Study I Portal Venous Flow Velocity - The mean velocity of the region of interest (ROI) was extracted for each one of the 25 phase images, and the time average was computed.
    Time Frame Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Chronic Hep C Patients Healthy Volunteers
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents. No Hep C
    Measure Participants 19 11
    Fasting
    10.5
    (3.2)
    11.5
    (2.8)
    Postprandial
    12.8
    (4.6)
    14.4
    (3.2)
    3. Primary Outcome
    Title LS-MRE for Sub-Study I
    Description Sub-Study I Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images.
    Time Frame Fasting State Scan (an average of 15 min) and Postprandial State Scan (an average of 15 min)

    Outcome Measure Data

    Analysis Population Description
    Sub Study I with 30 participants. The method failed in 3 of the patients, so no usable LS-MRE data was generated. 27 patients had usable data for PV flow and velocity, so they were included in the study.
    Arm/Group Title Chronic Hep C Patients Healthy Volunteers
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents. No Hep C
    Measure Participants 19 11
    Fasting
    4.9
    (1.4)
    1.8
    (0.2)
    Postprandial
    5.0
    (1.2)
    2.0
    (0.2)
    4. Primary Outcome
    Title True Diffusion Parameter (D)
    Description Sub-Study II True Diffusion Parameter - D- describes water diffusion in tissue independently from the effects of capillary perfusion; it is obtained from bi-exponential fitting of MRI diffusion signal acquired over a range of high and low diffusion-weighting factors (b-values) Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min) Scan

    Outcome Measure Data

    Analysis Population Description
    3 participants with scans not evaluable
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 57
    F0-F2
    1.06
    (0.21)
    F3-F4
    0.94
    (0.16)
    5. Primary Outcome
    Title LS-MRE Fibrosis State for Sub Study II
    Description Sub-Study II Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images. Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Only 38 participants had suitable MRE quality for analysis.
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 38
    F0-F2
    2.88
    (0.91)
    F3-F4
    5.16
    (0.95)
    6. Primary Outcome
    Title LS-TE
    Description Sub-Study II Liver Stiffness with transient elastography (TE) (LS-TE) - a non-invasive modality of liver fibrosis detection: a shear wave is sent into the liver through a small transducer attached to an ultrasound probe, and the velocity of the wave is measured as it passes through the liver; shear wave velocity is then converted to stiffness, measured in kilopascals (kPa) Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis
    Time Frame Fasting transient elastography, average duration 10 min

    Outcome Measure Data

    Analysis Population Description
    Only 46 participants had suitable TE quality for analysis.
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 46
    F0-F2
    9.55
    (6.85)
    F3-F4
    21.44
    (17.86)
    7. Primary Outcome
    Title MTT
    Description Sub-Study II Mean Transit Time (MTT) - Liver Mean Transit Time of Contrast Agent through the tissue of interest from Dynamic Contrast Enhanced MRI Fibrosis State/Score: F0-F2 - no signs of fibrosis to minimal fibrosis F3-F4 - fibrosis has spread and has connected to other areas on the liver that contain fibrosis or presence of cirrhosis
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Only 50 participants had suitable quality MRI for analysis
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 50
    F0-F2
    11.6
    (8.1)
    F3-F4
    18.8
    (9.1)
    8. Secondary Outcome
    Title Liver Upslope From DCE-MRI
    Description Sub-Study III Liver Upslope of MRI signal is defined as peak concentration to the time to reach peak concentration of gadolinium contrast agent in the liver tissue of interest, derived from dynamic contrast-enhanced MRI (DCE-MRI. Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts.
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 28
    HVPG <5mmHg
    0.011
    (0.011)
    HVPG>=5mmHg
    0.0007
    (0.0007)
    HPVG<10mmHg
    0.011
    (0.007)
    HPVG>=10mmHg
    0.0006
    (0.004)
    9. Secondary Outcome
    Title Liver Time to Peak (TTP) for PH
    Description Sub-Study III Liver Time to Peak (TTP) is defined as the time in seconds to reach peak concentration of gadolinium contrast agent in the liver tissue of interest, derived from dynamic contrast-enhanced MRI (DCE-MRI) Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) ≥5 mmHg Clinically Significant Portal Hypertension is defined as an HVPG ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts..
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 28
    HVPG<5mmHg
    40.99
    (22.20)
    HVPG>=5mmHg
    53.02
    (31.8)
    HVPG<10mmHg
    41.47
    (25.76)
    HVPG>=10mmHg
    69.45
    (41.98)
    10. Secondary Outcome
    Title LS-MRE Portal Hypertension for Sub Study III
    Description Sub-Study III Liver stiffness (LS) measured by magnetic resonance elastography (MRE) in kilopascal (kPa). Liver stiffness is assessed by mathematical modeling of compression waves propagation in the liver, as measured from MRE images. Portal Hypertension is defined as an HVPG ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    MRE was successful for liver stiffness measurements in 31 participants of the 34
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 31
    HVPG<5mmHg
    2.31
    (2.8)
    HVPG>=5mmHg
    5.14
    (2.57)
    HVPG<10mmHg
    3.88
    (3.16)
    HVPG>=10mmHg
    5.86
    (6.71)
    11. Secondary Outcome
    Title Spleen Volume
    Description Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Sub Study III with 34 participants
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 34
    HVPG<5mmHg
    246
    (252)
    HVPG>=5mmHg
    441
    (629)
    12. Secondary Outcome
    Title Spleen Caudocranial Diameter
    Description Sub-Study III Portal Hypertension is defined as an HVPG ≥5 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Sub Study III with 34 participants
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 34
    HVPG<5mmHg
    11.6
    (2.8)
    HVPG>=5mmHg
    14.0
    (4.8)
    13. Secondary Outcome
    Title PH Imaging Score
    Description Sub-Study III Portal Hypertension imaging composite score (based on the presence of varices, spleen size, presence of ascites). The imaging score is based on the number of variceal sites (0: absence of varices, 1: one variceal site, 2: two variceal sites, and 3: 3 or more variceal sites), volume of ascites (0: no ascites, 1: minimal perihepatic and perisplenic fluid, 2: intraperitoneal fluid without marked abdominal wall distension, and 3: fluid causing marked abdominal wall distension), and maximum craniocaudal diameter of the spleen (0: size less than 13 cm, 1: size between 13 and 15 cm, 2: size between 15 and 20 cm, and 3: size greater than 20 cm). Score from 0 to 9, with higher score indicating worse disease. Portal Hypertension is defined as an HVPG ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Sub Study III with 34 participants
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 34
    HVPG<5mmHg
    0
    (1)
    HVPG>=5mmHg
    2
    (5.25)
    HVPG<10
    1
    (1.5)
    HVPG>=10
    4
    (4.5)
    14. Secondary Outcome
    Title LSLU
    Description Sub-Study III Liver Stiffness to Liver Upslope ratio (LSLU) Portal Hypertension is defined as an HVPG ≥5 mmHg Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    31 of the 34 participants had LS-MRE and 28 of the 34 participants had Liver Upslope measurement from DCE-MRI
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 28
    HVPG<5mmHg
    192.72
    (195.65)
    HVPG>=5mmHg
    830.28
    (971.68)
    HVPG<10mmHg
    363.68
    (855.01)
    HVPG>10mmHg
    871.82
    (1354.31)
    15. Secondary Outcome
    Title Liver DV
    Description Sub Study III Liver Distribution Volume (DV) is the distribution volume of contrast agent in the tissue of interest defined as a percentage ratio of gadolinium material volume to the volume of the liver tissue of interest, as derived from DCE-MRI; in the case of a contrast agent with extracellular distribution, DV measures the intravascular and extravascular-extracellular volume. Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts.
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 28
    HVPG<10mmHg
    47.28
    (24.29)
    HVPG>=10mmHg
    77.25
    (111.01)
    16. Secondary Outcome
    Title Spleen TTP
    Description Sub Study III Spleen Time To Peak (TTP) - time to reach peak gadolinium concentration in spleen tissue of interest, derived from DCE-MRI. Clinically Significant Portal hypertension (CSPH), defined by hepatic venous pressure gradient (HVPG) ≥10 mmHg
    Time Frame Fasting State Multiparametric MRI Scan (an average of 60 min)

    Outcome Measure Data

    Analysis Population Description
    Among the 34 patients, 2 patients did not have DCE-MRI acquisition due to chronic renal insufficiency, 4 patients had non-usable DCE-MRI data because of major artifacts.
    Arm/Group Title Perfusion MRI
    Arm/Group Description chronic liver disease who underwent/will undergo liver biopsy or will undergo liver transplant or liver resection as part of standard care during the previous 6 months. Perfusion MRI: 1) Assess the role of a new FDA approved blood pool gadolinium contrast agent (gadofosveset trisodium, Ablavar, Lantheus) for the measurement of liver MR Perfusion, compared to extra-cellular contrast agents.
    Measure Participants 28
    HVPG<10mmHg
    15.46
    (16.65)
    HVPG>=10mmHg
    44.90
    (40.69)

    Adverse Events

    Time Frame 6 years
    Adverse Event Reporting Description
    Arm/Group Title Sub Study 1 Chronic Hep C Patients Sub Study 1 Health Volunteers Sub Study II Sub Study III Total Participants of the Substudies
    Arm/Group Description Quantitative Liver MRI Combining Phase Contrast Imaging, Elastography, and DWI: Assessment of Reproducibility and Postprandial Effect Description: Patients with liver disease who had portal vein (PV) flow parameters measured with phase contrast (PC) imaging, liver diffusion parameters measured with multiple b value diffusion-weighted imaging (DWI) and liver stiffness (LS) measured with MR elastography (MRE) in fasting conditions and after a meal challenge. Quantitative Liver MRI Combining Phase Contrast Imaging, Elastography, and DWI: Assessment of Reproducibility and Postprandial Effect Description: Healthy volunteers who had portal vein (PV) flow parameters measured with phase contrast (PC) imaging, liver diffusion parameters measured with multiple b value diffusion-weighted imaging (DWI) and liver stiffness (LS) measured with MR elastography (MRE) in fasting conditions and after a meal challenge. Arm/Group Title: Prospective Comparison of Magnetic Resonance Imaging to Transient Elastography and Serum Markers for Liver Fibrosis Detection Description: Chronic liver disease patients who underwent a multiparametric magnetic resonance imaging (MRI) protocol including diffusion�\weighted imaging (DWI), dynamic contrast�\enhanced (DCE)�\MRI and magnetic resonance elastography (MRE) in comparison with transient elastography (TE) for liver fibrosis detection. Noninvasive Prediction of Portal Pressure with MR Elastography and DCE�\MRI of the Liver and Spleen Description: Chronic liver disease patients who underwent HVPG measurement, MR elastography (MRE) and dynamic contrast�\enhanced MRI (DCE�\MRI) of the liver and spleen Total participants of Sub Study 1, Sub Study II, and Sub Study III
    All Cause Mortality
    Sub Study 1 Chronic Hep C Patients Sub Study 1 Health Volunteers Sub Study II Sub Study III Total Participants of the Substudies
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/11 (0%) 0/60 (0%) 0/34 (0%) 0/124 (0%)
    Serious Adverse Events
    Sub Study 1 Chronic Hep C Patients Sub Study 1 Health Volunteers Sub Study II Sub Study III Total Participants of the Substudies
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/11 (0%) 0/60 (0%) 0/34 (0%) 0/124 (0%)
    Other (Not Including Serious) Adverse Events
    Sub Study 1 Chronic Hep C Patients Sub Study 1 Health Volunteers Sub Study II Sub Study III Total Participants of the Substudies
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/11 (0%) 2/60 (3.3%) 0/34 (0%) 2/124 (1.6%)
    Nervous system disorders
    Fainting 0/19 (0%) 0/11 (0%) 1/60 (1.7%) 0/34 (0%) 1/124 (0.8%)
    Skin and subcutaneous tissue disorders
    Rash 0/19 (0%) 0/11 (0%) 1/60 (1.7%) 0/34 (0%) 1/124 (0.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Bachir Taouli
    Organization Icahn School of Medicine at Mount Sinai
    Phone 212-824-8475
    Email bachir.taouli@mountsinai.org
    Responsible Party:
    Bachir Taouli, Associate Professor, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT01600105
    Other Study ID Numbers:
    • GCO 09-1187
    First Posted:
    May 16, 2012
    Last Update Posted:
    Feb 7, 2020
    Last Verified:
    Jan 1, 2020