Safety and Efficacy of Gadobutrol 1.0 Molar (Gadavist) in Patients for Central Nervous System (CNS) Imaging

A Multicenter, Randomized, Double-blind, Crossover, Phase 3 Study to Determine the Safety and Efficacy of Gadobutrol 1.0 Molar (Gadavist) in Patients Referred for Contrast-enhanced MRI of the Central Nervous System (CNS)

This study involves the use of Magnetic Resonance Imaging (MRI) contrast agents called gadobutrol (Gadavist) Injection and ProHance Injection. The purpose of this study is to look at the safety (what are the side effects) and efficacy (how well does it work) of gadobutrol when used for taking MR images of the brain and spine. The results of the MRI with gadobutrol Injection will be compared to the results of MR images taken without contrast and with the results of the MR images taken with ProHance.

Study Overview

• Status: Completed
• Conditions: Central Nervous System Diseases; Diagnostic Imaging
• Intervention / Treatment: Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Drug: Gadoteridol (ProHance)

Detailed Description

Issues on safety will be addressed in Adverse Events section.

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
• Austria
  • Wien, Austria, 1090
    • Allgemeines Krankenhaus der Stadt Wien Universitätskliniken
  • Niederösterreich
    • Tulln, Niederösterreich, Austria, 3430
      • Landeskrankenhaus Donauregion Tulln
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4020
      • LNK Wagner Jauregg
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universitat Graz
• Colombia
  • Medellín, Colombia
    • Centro de Diagnostico Medico
  • Antioquia
    • Medellín, Antioquia, Colombia
      • Fundación Instituto de Alta tecnología médica de Antioquia
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia
      • Fundación Santa Fe de Bogotá - Hospital Universitario
  • Valle del Cauca
    • Cali, Valle del Cauca, Colombia
      • DIME Clinica Neurocardiovascular S.A.
• Germany
  • Berlin, Germany, 10117
    • Universitätsklinikum Charite zu Berlin
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf (UKE)
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Deutsches Krebsforschungszentrum
    • Karlsruhe, Baden-Württemberg, Germany, 76133
      • Städtisches Klinikum Karlsruhe gGmbH
    • Mannheim, Baden-Württemberg, Germany, 68167
      • Klinikum Mannheim gGmbH
  • Bayern
    • Augsburg, Bayern, Germany, 865156
      • Zentralklinikum Augsburg
    • Erlangen, Bayern, Germany, 91054
      • Universitätsklinikum Erlangen
    • München, Bayern, Germany, 81675
      • Klinikum rechts der Isar
    • München, Bayern, Germany, 81377
      • LMU Klinikum der Universität München - Großhadern
  • Brandenburg
    • Potsdam, Brandenburg, Germany, 14467
      • Klinikum Ernst von Bergmann
  • Hessen
    • Frankfurt, Hessen, Germany, 60488
      • Krankenhaus Nordwest
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Kliniken der Medizinischen Hochschule Hannover
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
      • Medizinische Einrichtungen der Universität Bonn
    • Dortmund, Nordrhein-Westfalen, Germany, 44263
      • Medizinisches Versorgungszentrum Prof. Dr. D. Uhlenbrock
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Universitätsklinikum Köln
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • Universitätskliniken des Saarlandes
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Medizinische Fakultät Carl Gustav Carus
    • Leipzig, Sachsen, Germany, 04103
      • Universitatsklinikum Leipzig AoR
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Klinikum der Christian-Albrechts-Universität
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
      • HELIOS Klinikum Erfurt GmbH
• India
  • Lucknow, India, 226 014
    • Sanjay Gandhi Post Graduate Institute of Medical Sciences
  • Mumbai, India, 400020
    • Bombay Hospital, Institute of Medical sciences
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 252002
      • CT /MRI centre
  • Maharashtra
    • Mumbai, Maharashtra, India, 400004
      • Piramal Diagnostic- Jankharia Imaging
• Japan
  • Kyoto, Japan, 616-8255
    • Utano National Hospital
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Osaka, Japan, 537-8511
    • Osaka Medical Center for Cancer and Cardiovascular Diseases
  • Osaka, Japan, 540-0006
    • Osaka National Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 454-0933
      • Nagoya Kyoritsu Clinic
    • Nagoya, Aichi, Japan, 454-0933
      • Nagoya Kyoritsu Hospital
    • Nagoya, Aichi, Japan, 457-8510
      • Social Insurance Chukyo Hospital
  • Hyogo
    • Himeji, Hyogo, Japan, 670-8520
      • Himeji Medical Center
    • Himeji, Hyogo, Japan, 672-8501
      • Himeji Central Hospital
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
    • Kobe, Hyogo, Japan, 650-0047
      • Institute of Biomedical Research and Innovation
    • Kobe, Hyogo, Japan, 654-0047
      • Shinsuma Hospital
  • Osaka
    • Kishiwada, Osaka, Japan, 596-8522
      • Kishiwada Tokushukai Hospital
  • Yamaguchi
    • Shimonoseki, Yamaguchi, Japan, 750-0061
      • Shimonoseki Kosei Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Genève, Switzerland, 1211
    • Hôpital Cantonal Universitaire de Genève
  • Luzern, Switzerland, 6000
    • Luzerner Kantonsspital
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • Universitatsspital Basel
  • Sankt Gallen
    • St. Gallen, Sankt Gallen, Switzerland, 9007
      • Kantonsspital St. Gallen
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • West Alabama Research, Inc.
    • Tuscaloosa, Alabama, United States, 35406
      • Achieve Clinical Research, LLC
  • California
    • Los Gatos, California, United States, 95032
      • Los Gatos MRI
    • Newport Beach, California, United States, 92658-6100
      • Hoag Memorial Hospital Presbyterian
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Medical Group, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Jacksonville
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
  • Kansas
    • Atchison, Kansas, United States, 66002
      • Atchison Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital/Health System
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Hospital System
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Shields MRI - Brockton
    • West Roxbury, Massachusetts, United States, 02132
      • VA Boston Healthcare System-West Roxbury Division
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Mexico
    • Alburquerque, New Mexico, United States, 87131
      • University of New Mexico School of Medicine
  • New York
    • Kingston, New York, United States, 12401
      • Kingston Neurological Associates, PC
    • New York, New York, United States, 10003
      • NYU Hospital for Joint Diseases
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is at least 18 years of age
• Is referred for a contrast-enhanced MRI of the CNS based on current clinical symptoms or results of a previous imaging procedure
• Has been fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA) as applicable, and has consented to participate

Exclusion Criteria:

• Has any contraindication to the MRI examinations or the use of Gd-containing contrast agents
• Has a history of severe allergic or anaphylactoid reaction to any allergen including drugs and contrast agents
• Has severe cardiovascular disease (eg, known long QT syndrome, acute myocardial infarction [< 14 days], unstable angina, congestive heart failure New York Heart Association class IV) or acute stroke (< 48 hours)- Patients with acute renal insufficiency of any severity due to hepato-renal syndrome or in the perioperative liver transplantation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gadobutrol then Gadoteridol; Participants received a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous) in Period 1 and a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v. in Period 2.	Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Participants received a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous); Drug: Gadoteridol (ProHance); Participants received a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v.
Experimental: Gadoteridol then Gadobutrol; Participants received a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v. in Period 1 and a single dose of gadobutrol 0.1 mmol/kg bw via i.v. in Period 2.	Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Participants received a single dose of gadobutrol 0.1 mmol/kg body weight (bw) via i.v. (intravenous); Drug: Gadoteridol (ProHance); Participants received a single dose of gadoteridol at the approved dose, 0.1 mmol/kg bw, via i.v.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 1 (BR1)	BR1 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 2 (BR2)	BR2 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Blinded Reader 3 (BR3)	BR3 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced Magnetic Resonance Imaging (MRI) Compared to Unenhanced MRI by Average Reader (AR)	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers	The blinded readers evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another to determine the total number of lesions.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1)	BR1 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2)	BR2 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3)	BR3 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR)	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1)	BR1 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 2 (BR2)	BR2 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 3 (BR3)	BR3 evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader (AR)	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadoteridol
Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader	The AR analysis used the mean of the values for the 3 blinded readers	Up to 2 hours after injection of gadoteridol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader	The AR analysis used the mean of the values for the 3 blinded readers.	Up to 2 hours after injection of gadobutrol or gadoteridol
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader	The AR analysis used the mean of the values for the 3 blinded readers	Up to 2 hours after injection of gadobutrol or gadoteridol
Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Unenhanced MRI by Blinded Readers	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another and determined the number of lesion from each.	Up to 2 hours after injection of gadobutrol
Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadoteridol-enhanced MRI or for Unenhanced MRI by Average Reader	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadoteridol-enhanced MRIs in another and determined the number of lesion from each.	Up to 2 hours after injection of gadoteridol
Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader	The AR analysis used the mean of the values for the 3 blinded readers. The 3 BRs evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs in one session and the images from the combined unenhanced and gadoteridol-enhanced MRIs in another and determined the number of lesion from each.	Up to 2 hours after injection of gadobutrol or gadoteridol
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadobutrol-enhanced MRIs. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another to determine the total number of lesions.	Up to 2 hours after injection of gadobutrol
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadobutrol-enhanced MRIs. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadobutrol-enhanced MRIs. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadoteridol-enhanced MRIs. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadoteridol
Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadoteridol-enhanced MRIs in another to determine the total number of lesions.	Up to 2 hours after injection of gadoteridol
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Normal Structures for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadoteridol-enhanced MRIs. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadoteridol
Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the unenhanced MRI and the images from the combined unenhanced and gadoteridol-enhanced MRIs. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadoteridol
Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs and the images from the combined unenhanced and gadoteridol-enhanced MRIs. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol or gadoteridol
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs and the combined unenhanced and gadoteridol-enhanced MRIs in another to determine the total number of lesions.	Up to 2 hours after injection of gadobutrol or gadoteridol
Scores for Contrast Enhancement, Border Delineation and Internal Morphology for Normal Structures for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs and the images from the combined unenhanced and gadoteridol-enhanced MRIs. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol or gadoteridol
Scores for Contrast Enhancement, Border Delineation and Internal Morphology for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The clinical investigators evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs and the images from the combined unenhanced and gadoteridol-enhanced MRIs. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. Border delineation was scored on a 4-point scale where 1 = no or unclear delineation and 4 = excellent delineation. Internal morphology was scored on a 3-point scale where 1 = poorly visible and 3 = sufficiently visible.	Up to 2 hours after injection of gadobutrol or gadoteridol
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The majority reader diagnosis was the diagnosis provided by at least 2 of the BRs. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the majority reader diagnoses for the combined unenhanced/gadobutrol-enhanced and the unenhanced MR images were evaluated for consistency with the final clinical diagnosis.	Up to 2 hours after injection of gadobutrol
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the investigator diagnoses for the combined unenhanced/gadobutrol-enhanced and the unenhanced MR images were evaluated for consistency with the final clinical diagnosis.	Up to 2 hours after injection of gadobutrol
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The majority reader diagnosis was the diagnosis provided by at least 2 of the BRs. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the majority reader diagnoses for the combined unenhanced/gadoteridol-enhanced and the unenhanced MR images were evaluated for consistency with the final clinical diagnosis.	Up to 2 hours after injection of gadoteridol
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the investigator diagnoses for the combined unenhanced/gadoteridol-enhanced and the unenhanced MR images were evaluated for consistency with the final clinical diagnosis.	Up to 2 hours after injection of gadoteridol
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader	The majority reader diagnosis was the diagnosis provided by at least 2 of the BRs. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the majority reader diagnoses for the combined unenhanced/gadobutrol-enhanced and the combined unenhanced/gadoteridol-enhanced MR images were evaluated for consistency with the final clinical diagnosis.	Up to 2 hours after injection of gadobutrol or gadoteridol
Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. The accuracy of the clinical investigator diagnoses for the combined unenhanced/gadobutrol-enhanced and the combined unenhanced/gadoteridol-enhanced MR images were evaluated for consistency with the final clinical diagnosis.	Up to 2 hours after injection of gadobutrol or gadoteridol
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) matches the standard of truth for the presence or absence of abnormal brain tissue.	Up to 2 hours after injection of gadobutrol
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly detects abnormal brain tissue as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly excludes abnormal brain tissue as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) matches the standard of truth for the presence or absence of abnormal brain tissue.	Up to 2 hours after injection of gadoteridol
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) correctly detects abnormal brain tissue as defined by the independent truth committee.	Up to 2 hours after injection of gadoteridol
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) correctly excludes abnormal brain tissue as defined by the independent truth committee.	Up to 2 hours after injection of gadoteridol
Accuracy of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) matches the standard of truth for the presence or absence of abnormal brain tissue.	Up to 2 hours after injection of gadobutrol or gadoteridol
Sensitivity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) correctly detects abnormal brain tissue as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol or gadoteridol
Specificity of Detection of Normal/Abnormal Brain Tissue for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader Using T1-weighted (T1w) Images	The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs for the T1w assessment (normal or abnormal). The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) correctly excludes abnormal brain tissue as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol or gadoteridol
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.	Up to 2 hours after injection of gadobutrol
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.	Up to 2 hours after injection of gadobutrol
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadobutrol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.	Up to 2 hours after injection of gadoteridol
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) correctly detects malignant lesions as defined by the independent truth committee	Up to 2 hours after injection of gadoteridol
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadoteridol
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.	Up to 2 hours after injection of gadoteridol
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadoteridol
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (unenhanced or Gadoteridol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadoteridol
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.	Up to 2 hours after injection of gadobutrol or gadoteridol
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol or gadoteridol
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority Reader	The presence of malignant lesions was derived from the diagnoses given on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The majority reader diagnosis was the diagnosis provided by at least 2 of the 3 BRs. The final clinical diagnosis was provided by an independent truth committee not using the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol or gadoteridol
Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Accuracy = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) matches the standard of truth for the presence or absence of malignant lesions.	Up to 2 hours after injection of gadobutrol or gadoteridol
Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Sensitivity = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) correctly detects malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol or gadoteridol
Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The presence of malignant lesions was derived from the diagnoses given by the investigator on the evaluation of the unenhanced image set and the combined unenhanced/enhanced image sets. The final clinical diagnosis was provided by an independent truth committee following evaluation of findings from referral through a 3-month follow-up period, not including the study-specific MR image sets. Specificity = percentage of participants for which the imaging modality (Gadobutrol-enhanced or Gadoteridol-enhanced) correctly excludes malignant lesions as defined by the independent truth committee.	Up to 2 hours after injection of gadobutrol or gadoteridol
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader	The BRs recorded his/her confidence in diagnosis for the unenhanced MR image set and the combined unenhanced/enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident. The AR score was the mean of the means of the 3 BRs.	Up to 2 hours after injection of gadobutrol
Diagnostic Confidence for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average Reader	The BRs recorded his/her confidence in diagnosis for the unenhanced MR image set and the combined unenhanced/enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident. The AR score was the mean of the means of the 3 BRs.	Up to 2 hours after injection of gadoteridol
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average Reader	The BRs recorded his/her confidence in diagnosis for the combined unenhanced/enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident. The AR score was the mean of the means of the 3 BRs.	Up to 2 hours after injection of gadobutrol or gadoteridol
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The investigator recorded his/her confidence in diagnosis for the unenhanced MR image set and the combined unenhanced/gadobutrol-enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident.	Up to 2 hours after injection of gadobutrol
Diagnostic Confidence for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator	The investigator recorded his/her confidence in diagnosis for the unenhanced MR image set and the combined unenhanced/gadoteridol-enhanced MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident.	Up to 2 hours after injection of gadoteridol
Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical Investigator	The investigator recorded his/her confidence in diagnosis for the combined unenhanced/gadobutrol-enhanced MR image sets and the combined unenhanced/gadoteridol MR image sets. The degree of confidence was rated on a 4-point scale where 1 = not confident and 4 = very confident.	Up to 2 hours after injection of gadobutrol or gadoteridol
Comparison of Image Quality Between Gadobutrol and Gadoteridol by Blinded Readers	The BRs evaluated the relative image quality of the gadobutrol-enhanced T1w MR images and the gadoteridol-enhanced T1w MR images in a paired fashion on a 5-point scale where 1 = image on right was worse, 2 = image on right was slightly worse, 3 = both images were the same, 4 = image on right was slightly better, and 5 = image on right was better.	Up to 2 hours after injection of gadobutrol or gadoteridol
Percentage of Participants for Which Blinded Readers Said Image Quality Was Higher	Percentage of participants for which blinded readers said image quality was higher	Up to 2 hours after injection of gadobutrol or gadoteridol
Assessment of the Number of Contrast-enhanced Lesions for Gadobutrol and Gadoteridol by Blinded Readers	Two BRs independently provided the number of contrast-enhanced lesions for gadobutrol and gadoteridol. In cases of disagreement between the readers, an independent adjudicator provided the number of contrast-enhanced lesions. The adjudicator results were used in the analysis in the cases of disagreement between the original readers	Up to 2 hours after injection of gadobutrol or gadoteridol
Percentage of Lesion Enhancement From Unenhanced to Combined Unenhanced/Enhanced for Gadobutrol and Gadoteridol by Blinded Readers	From the quantitative signal intensity values assessed by the BR, the percentage of lesion enhancement from unenhanced to combined unenhanced/enhanced was calculated.	Up to 2 hours after injection of gadobutrol or gadoteridol

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: July 1, 2008
• First Posted (Estimate): July 3, 2008

Study Record Updates

• Last Update Posted (Estimate): December 30, 2014
• Last Update Submitted That Met QC Criteria: December 8, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Patients referred for a contrast-enhanced MRI of the CNS; CNS Imaging
• Additional Relevant MeSH Terms: Nervous System Diseases; Central Nervous System Diseases
• Other Study ID Numbers: 91681; 2007-004746-33 (EudraCT Number); 310123 (Other Identifier: Company Internal)