The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study

BACKGROUND: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. • The value of ARIA-E detection, classification and monitoring using subtraction was assessed. • Validation of an established ARIA-E rating scale, recommendations for improvement are reported. • Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement

USING SUBTRACTION MRI TO IMPROVE THE DETECTION OF AMYLOID-RELATED IMAGING ABNORMALITIES WITH EDEMA OR EFFUSION (ARIA-E) IN PATIENTS AFFECTED BY ALZHEIMER’S DISEASE RECEIVING IMMUNOTHERAPY: AN INTER-OBSERVER STUDY

Background: Amyloid-s plaques are considered the hallmark of Alzheimer's disease (AD). Immunotherapeutic strategies targeting Abeta have shown promising results, although they are associated with adverse events, including amyloid-related imaging abnormalities with edema and effusion (ARIA-E). A magnetic resonance imaging (MRI) scale to improve the detection and classification of these lesions has recently been approved. The purpose of this study was to investigate the use of the subtraction technique as an adjunct to standard FLAIR to improve the detection of ARIA-E using an established rating score. Methods:We included 75 AD patients who were submitted to Bapineuzumab treatment in a phase II study, 29 of whom developed ARIA-E. Five experienced neuroradiologists rated the brain MRI scans with and without using subtraction images after image registration. The accuracy of detection, intraclass correlation coefficient (ICC) and positive and negative specific agreement were calculated. Results: The sensitivity and specificity of ARIA-E cases detection per individual rater were excellent using both native images (1.00, 0.957, respectively) and subtraction images (0.966, 0.891, respectively). Overall, the detection rate with subtraction images resulted in higher sensitivity (0.966) and lower specificity rate (0.970) compared to native images (0.959, 0.991, respectively). ICC scores in both groups ranged from good to excellent, except for gyral swelling (moderate). Excellent negative specific agreement among all ARIA-E imaging features and good positive agreement were demonstrated in both groups. Positive agreement for subtraction images increased significantly when combining sulcal hyperintensity and gyral swelling. Conclusions: The use of subtraction imaging for the evaluation of ARIA-E may improve the detection of these abnormalities and the classification of their features. Nevertheless, this method would benefit from isotropic acquisition, enhanced training, and modification of the ARIA-E rating scale to lump parenchymal and sulcal hyperintensity or swelling. (Table Presented)

The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer’s patients: An interobserver study

Background: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer’s disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. Purpose: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. Methods: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. Results: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. Conclusion: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. Key Points: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer’s patients.• The value of ARIA-E detection, classification and monitoring using subtraction was assessed.• Validation of an established ARIA-E rating scale, recommendations for improvement are reported.• Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement