Related Experiment Video
Updated: May 9, 2026

Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Relationship of Inferior Frontal Sulcal Hyperintensities with Amyloid-Related Imaging Abnormalities
Saurabh Rohatgi1, Nima Omid-Fard2, Shenghua Zhu2
1From the Division of Neuroradiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School. Boston, MA, 02114. srohatgi@mgh.harvard.edu.
Objective:
Anti-amyloid immunotherapies used to treat Alzheimer's disease (AD) are often associated with amyloid-related imaging abnormalities (ARIA). We aim to indirectly assess glymphatic function by using inferior frontal sulcal hyperintensity (IFSH) as a biomarker in patients receiving anti-amyloid therapy, both with and without ARIA, as well as in healthy controls. We hypothesize that patients who develop ARIA will have higher IFSH scores than non-ARIA patients and healthy controls.
Methods:
Eligible AD patients who received anti-amyloid treatment were included in our retrospectively collected dataset. Only scans performed at 3T were used. Inter-rater reliability was evaluated and statistical analyses of IFSH scores and demographic data were performed to compare between groups. Additionally, within-subject analysis was used to compare the baseline and ARIA scans. Significance set at P < 0.05.
Results:
A total of 104 patients were selected based on the study criteria, of whom 60 had a clinical diagnosis of dementia. 36 patients developed ARIA, while 24 did not develop ARIA. 23 were age-matched healthy controls, and 21 were young healthy controls. Inter-rater reliability between the two readers was concordant when using quadratic weights appropriate for ordinal data (κ (w) = 0. 91, 95% CI 0.86-0.95). IFSH was significantly higher in the older age cohorts compared to young healthy controls (median 3.5 [IQR 2.5-5] versus 0 [0-1], P<0.001), with no significant difference between the dementia and healthy elderly groups (3.25 [3-4.875] versus 3.5 [2.5-5]). Among dementia patients on anti-amyloid therapy, significantly higher IFSH was observed in ARIA patients (at time of ARIA scan) compared to their non-ARIA counterparts (3.75 [3-5] versus 3 [2-4], P= 0.04). There was no significant difference in IFSH score between baseline and ARIA scans (P = 0.16).
Conclusion:
IFSH was higher among dementia patients on anti-amyloid therapy with ARIA than among their non-ARIA counterparts. This supports its role as a potential biomarker of glymphatic dysfunction, although its utility on an individual basis is limited. Future prospective studies could benefit from incorporating IFSH as a variable, particularly if glymphatic therapies become a reality.
