MedPath

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

Phase 3
Completed
Conditions
Diagnostic Imaging
Central Nervous System Diseases
Interventions
Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
Drug: Gadoteridol (ProHance)
Registration Number
NCT00709852
Lead Sponsor
Bayer
Brief Summary

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.

Detailed Description

Issues on safety will be addressed in Adverse Events section.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
402
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Gadobutrol then GadoteridolGadobutrol (Gadavist, Gadovist, BAY86-4875)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.
Gadobutrol then GadoteridolGadoteridol (ProHance)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.
Gadoteridol then GadobutrolGadobutrol (Gadavist, Gadovist, BAY86-4875)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.
Gadoteridol then GadobutrolGadoteridol (ProHance)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.
Primary Outcome Measures
NameTimeMethod
Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded ReadersUp to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

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)Up to 2 hours after injection of gadobutrol

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants for Which Blinded Readers Said Image Quality Was HigherUp to 2 hours after injection of gadobutrol or gadoteridol

Percentage of participants for which blinded readers said image quality was higher

Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average ReaderUp to 2 hours after injection of gadoteridol

The AR analysis used the mean of the values for the 3 blinded readers

Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Unenhanced MRI by Blinded ReadersUp to 2 hours after injection of gadobutrol

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.

Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadoteridol

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.

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) ImagesUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Scores for Three Visualization Parameters (Contrast Enhancement, Border Delineation and Internal Morphology) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average ReaderUp to 2 hours after injection of gadoteridol

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.

Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadobutrol-enhanced MRI or for Combined Unenhanced/Gadoteridol-enhanced MRI by Average ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol

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.

Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

The AR analysis used the mean of the values for the 3 blinded readers

Percentage of Participants With More Lesions Detected for Combined Unenhanced/Gadoteridol-enhanced MRI or for Unenhanced MRI by Average ReaderUp to 2 hours after injection of gadoteridol

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.

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 InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

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 ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

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.

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) ImagesUp to 2 hours after injection of gadobutrol

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.

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 ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

The AR analysis used the mean of the values for the 3 blinded readers.

Scores for Two Visualization Parameters (Border Delineation and Internal Morphology) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Number of Lesions for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

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 InvestigatorUp to 2 hours after injection of gadoteridol

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.

Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

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 InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

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 InvestigatorUp to 2 hours after injection of gadobutrol

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.

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 InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

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 InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

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) ImagesUp to 2 hours after injection of gadobutrol

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.

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) ImagesUp to 2 hours after injection of gadobutrol

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.

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) ImagesUp to 2 hours after injection of gadoteridol

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.

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) ImagesUp to 2 hours after injection of gadoteridol

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.

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) ImagesUp to 2 hours after injection of gadoteridol

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.

Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadoteridol

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

Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadoteridol

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.

Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol

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.

Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol

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.

Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

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) ImagesUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol

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.

Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

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) ImagesUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Majority ReaderUp to 2 hours after injection of gadoteridol

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.

Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Assessment of the Number of Contrast-enhanced Lesions for Gadobutrol and Gadoteridol by Blinded ReadersUp to 2 hours after injection of gadobutrol or gadoteridol

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

Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Majority ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average ReaderUp to 2 hours after injection of gadobutrol

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.

Diagnostic Confidence for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadoteridol

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.

Comparison of Image Quality Between Gadobutrol and Gadoteridol by Blinded ReadersUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Percentage of Lesion Enhancement From Unenhanced to Combined Unenhanced/Enhanced for Gadobutrol and Gadoteridol by Blinded ReadersUp to 2 hours after injection of gadobutrol or gadoteridol

From the quantitative signal intensity values assessed by the BR, the percentage of lesion enhancement from unenhanced to combined unenhanced/enhanced was calculated.

Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Diagnostic Confidence for Combined Unenhanced/Gadoteridol-enhanced MRI Compared to Unenhanced MRI by Average ReaderUp to 2 hours after injection of gadoteridol

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.

Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Combined Unenhanced/Gadoteridol-enhanced MRI by Average ReaderUp to 2 hours after injection of gadobutrol or gadoteridol

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.

Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical InvestigatorUp to 2 hours after injection of gadobutrol

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.

Trial Locations

Locations (79)

Piramal Diagnostic- Jankharia Imaging

🇮🇳

Mumbai, Maharashtra, India

Universitätsklinikum Erlangen

🇩🇪

Erlangen, Bayern, Germany

LMU Klinikum der Universität München - Großhadern

🇩🇪

München, Bayern, Germany

Klinikum rechts der Isar

🇩🇪

München, Bayern, Germany

Institute of Biomedical Research and Innovation

🇯🇵

Kobe, Hyogo, Japan

University of Florida - Jacksonville

🇺🇸

Jacksonville, Florida, United States

Universitätskliniken des Saarlandes

🇩🇪

Homburg, Saarland, Germany

Klinikum Ernst von Bergmann

🇩🇪

Potsdam, Brandenburg, Germany

Medizinische Einrichtungen der Universität Bonn

🇩🇪

Bonn, Nordrhein-Westfalen, Germany

Krankenhaus Nordwest

🇩🇪

Frankfurt, Hessen, Germany

Kliniken der Medizinischen Hochschule Hannover

🇩🇪

Hannover, Niedersachsen, Germany

Universitätsklinikum Köln

🇩🇪

Köln, Nordrhein-Westfalen, Germany

Universitätsklinikum Charite zu Berlin

🇩🇪

Berlin, Germany

Utano National Hospital

🇯🇵

Kyoto, Japan

Osaka National Hospital

🇯🇵

Osaka, Japan

Osaka General Medical Center

🇯🇵

Osaka, Japan

University of Maryland Hospital System

🇺🇸

Baltimore, Maryland, United States

Johns Hopkins Hospital/Health System

🇺🇸

Baltimore, Maryland, United States

Shields MRI - Brockton

🇺🇸

Brockton, Massachusetts, United States

VA Boston Healthcare System-West Roxbury Division

🇺🇸

West Roxbury, Massachusetts, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Wales, Australia

St George Hospital

🇦🇺

Kogarah, New South Wales, Australia

Westmead Hospital

🇦🇺

Westmead, New South Wales, Australia

Monash Medical Centre

🇦🇺

Clayton, Victoria, Australia

Landeskrankenhaus Donauregion Tulln

🇦🇹

Tulln, Niederösterreich, Austria

LNK Wagner Jauregg

🇦🇹

Linz, Oberösterreich, Austria

Medizinische Universität Graz

🇦🇹

Graz, Steiermark, Austria

Allgemeines Krankenhaus der Stadt Wien Universitätskliniken

🇦🇹

Wien, Austria

Fundación Instituto de Alta tecnología médica de Antioquia

🇨🇴

Medellín, Antioquia, Colombia

Fundación Santa Fe de Bogotá - Hospital Universitario

🇨🇴

Bogotá, Cundinamarca, Colombia

Städtisches Klinikum Karlsruhe gGmbH

🇩🇪

Karlsruhe, Baden-Württemberg, Germany

Achieve Clinical Research, LLC

🇺🇸

Tuscaloosa, Alabama, United States

Los Gatos MRI

🇺🇸

Los Gatos, California, United States

Hoag Memorial Hospital Presbyterian

🇺🇸

Newport Beach, California, United States

Redwood Regional Medical Group, Inc.

🇺🇸

Santa Rosa, California, United States

NorthShore University HealthSystem-Evanston Hospital

🇺🇸

Evanston, Illinois, United States

University of New Mexico School of Medicine

🇺🇸

Alburquerque, New Mexico, United States

Kingston Neurological Associates, PC

🇺🇸

Kingston, New York, United States

The Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

NYU Hospital for Joint Diseases

🇺🇸

New York, New York, United States

Hospital of the University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Atchison Hospital

🇺🇸

Atchison, Kansas, United States

Klinikum der Christian-Albrechts-Universität

🇩🇪

Kiel, Schleswig-Holstein, Germany

Universitätsspital Basel

🇨🇭

Basel, Basel-Stadt, Switzerland

Washington University School of Medicine

🇺🇸

St. Louis, Missouri, United States

West Alabama Research, Inc.

🇺🇸

Birmingham, Alabama, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

University of Washington Medical Center

🇺🇸

Seattle, Washington, United States

Shinsuma Hospital

🇯🇵

Kobe, Hyogo, Japan

Centro de Diagnostico Medico

🇨🇴

Medellín, Colombia

Medizinisches Versorgungszentrum Prof. Dr. D. Uhlenbrock

🇩🇪

Dortmund, Nordrhein-Westfalen, Germany

HELIOS Klinikum Erfurt GmbH

🇩🇪

Erfurt, Thüringen, Germany

Nagoya Kyoritsu Hospital

🇯🇵

Nagoya, Aichi, Japan

Universitätsklinikum Leipzig AöR

🇩🇪

Leipzig, Sachsen, Germany

Nagoya Kyoritsu Clinic

🇯🇵

Nagoya, Aichi, Japan

Himeji Central Hospital

🇯🇵

Himeji, Hyogo, Japan

Sanjay Gandhi Post Graduate Institute of Medical Sciences

🇮🇳

Lucknow, India

Shimonoseki Kosei Hospital

🇯🇵

Shimonoseki, Yamaguchi, Japan

Luzerner Kantonsspital

🇨🇭

Luzern, Switzerland

Universitätsklinikum Hamburg Eppendorf (UKE)

🇩🇪

Hamburg, Germany

Zentralklinikum Augsburg

🇩🇪

Augsburg, Bayern, Germany

Social Insurance Chukyo Hospital

🇯🇵

Nagoya, Aichi, Japan

Kishiwada Tokushukai Hospital

🇯🇵

Kishiwada, Osaka, Japan

Osaka Medical Center for Cancer and Cardiovascular Diseases

🇯🇵

Osaka, Japan

Klinikum Mannheim gGmbH

🇩🇪

Mannheim, Baden-Württemberg, Germany

CT /MRI centre

🇮🇳

Indore, Madhya Pradesh, India

Medizinische Fakultät Carl Gustav Carus

🇩🇪

Dresden, Sachsen, Germany

Bombay Hospital, Institute of Medical sciences

🇮🇳

Mumbai, India

Himeji Medical Center

🇯🇵

Himeji, Hyogo, Japan

Kobe City Medical Center General Hospital

🇯🇵

Kobe, Hyogo, Japan

DIME Clinica Neurocardiovascular S.A.

🇨🇴

Cali, Valle del Cauca, Colombia

Kantonsspital St. Gallen

🇨🇭

St. Gallen, Sankt Gallen, Switzerland

Inselspital Bern

🇨🇭

Bern, Switzerland

Hôpital Cantonal Universitaire de Genève

🇨🇭

Genève, Switzerland

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Aurora Saint Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Deutsches Krebsforschungszentrum

🇩🇪

Heidelberg, Baden-Württemberg, Germany

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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