Arterial Spin-Labeling MRI at the Cortical-CSF Interface: A Novel Biomarker in Alzheimer Disease.

BACKGROUND/

OBJECTIVE

Arterial spin-labeling (ASL) MRI can measure perfusion signal adjacent to CSF spaces and may provide information regarding CSF-adjacent water transport physiology. We developed an automated pipeline to extract cortical-CSF interface (IF) perfusion for comparison between Alzheimer disease (AD) and cognitively normal controls.

METHODS

In this retrospective study, participants with AD and cognitively normal controls with ASL and 3D T1-weighted MRI were included. Parenchymal cerebral blood flow (CBF) was evaluated globally (whole brain, gray matter, white matter) and across 12 brain regions. IF-perfusion values were quantified using an automated pipeline with tissue segmentation, registration, partial-volume-aware masking, and arterial-signal exclusion. Multivariable sensitivity analysis was performed, adjusting for age, sex, scanner vendor, and acquisition site. Predictive modeling was performed using LASSO-regularized logistic regression with nested repeated stratified cross-validation, and feature contributions were summarized using SHAP.

RESULTS

A total of 51 patients with AD, age (median: 73 years) and 53 cognitively normal subjects (median age: 69) were included. Global CBF did not differ between groups. However, IF-perfusion values were significantly lower in AD (median 4.4, IQR 3.2-4.8) than in controls (median 5.2, IQR 4.5-6.3; p < 0.001). In multivariable analysis, AD remained independently associated with lower IF-perfusion after adjustment for age, sex, scanner vendor, and acquisition site (β = -1.88, 95% CI: -3.52 to -0.25; p = 0.025). In LASSO-regularized logistic regression model, only IF-perfusion and cuneus-CBF remained as significant contributing features for the prediction of AD probability with the highest contribution from IF. The final model showed mean ROC-AUC 0.81 in the training and AUC of 0.78 in the testing dataset.

CONCLUSION

ASL-derived IF-perfusion is reduced in AD and may represent a promising imaging marker of altered CSF-adjacent water transport physiology. Further validation against established biomarkers of CSF dynamics and clearance pathways is warranted.