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

• 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR1 (reader 1 of 3) evaluated the images from the unenhanced magnetic resonance imaging (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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR2 (reader 2 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR3 (reader 3 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Readers [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The 3 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 Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The clinical investigators 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. The data for "contrast enhancement - unenhanced" were not collected for the clinical investigators.
  
  
• Number of Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The clinical investigators 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 Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Blinded Reader 1 (BR1) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR1 (reader 1 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR2 (reader 2 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR3 (reader 3 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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 1 (BR1) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR1 (reader 1 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR2 (reader 2 of 3) 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 3 (BR3) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  BR3 (reader 3 of 3) 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) [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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 Contrast Enhancement for Lesions for Combined Unenhanced/Gadobutrol-enhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The clinical investigators evaluated the images from the combined unenhanced and gadobutrol-enhanced MRIs. Contrast enhancement was scored on a 4-point scale where 1 = no enhancement and 4 = excellent enhancement. The data for contrast enhancement - gadobutrol combined was shown below.
  
  
• 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 [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The clinical investigators evaluated the images from the unenhanced MRI in one session and the images from the combined unenhanced and gadobutrol-enhanced MRIs in another. 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 Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The clinical investigators 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 (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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 was the percentage of the exact matches with the final clinical diagnosis.
  
  
• Percentage (Per.) of the Exact Diagnostic Matches (Accuracy of Diagnosis) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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 was the percentage of the exact matches 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) Images [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• 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 [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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) Images [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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
  
  
• Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Majority Reader [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• Accuracy of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• Sensitivity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• Specificity of Detection of Malignant Lesions (ML) for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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.
  
  
• Diagnostic Confidence for Combined Unenhanced/Gadobutrol-enhanced MRI Compared to Unenhanced MRI by Average Reader [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  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 Unenhanced MRI by Clinical Investigator [ Time Frame: Up to 2 hours after injection of gadobutrol ] [ Designated as safety issue: No ]
  The investigator 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.
  
  

Issues on safety will be addressed in Adverse Events section.