Segmentation and Morphometry of Intracranial Internal Carotid Artery Calcification in Relation to Brain Atrophy

Authors

• Xiao Xu, University of Southern California
• Nikhil N. Chaudhari, University of Southern California
• Phoebe E. Imms, University of Southern California
• Nahian F. Chowdhury, University of Southern California
• Fangyun C. Liu, University of Southern California
• Jorge A. Solis Galvan, University of Southern California
• Bavrina Bigjahan, The University of Illinois at Chicago
• Grant Schleifer, Harvard Medical School
• Maria Ashna, University of Southern California
• Blake Hannagan, University of Southern California
• Giuseppe Barisano, Stanford University
• Daniel K. Cummings, Chapman University
• Daniel Eid Rodriguez, Universidad Mayor de San Simon
• Paul L. Hooper, Chapman University
• Edmond Seabright, Université Mohammed VI Polytechnic
• Randall C. Thompson, Saint Luke’s Mid America Heart Institute
• Benjamin C. Trumble, Arizona State University
• Michael D. Gurven, University of California, Santa BarbaraFollow
• Jonathan Stieglitz, Toulouse School of Economics
• Caleb E. Finch, University of Southern California
• M. Linda Sutherland, MemorialCare Health Systems
• James D. Sutherland, MemorialCare Health Systems
• Helena C. Chui, University of Southern California
• Margaret Gatz, University of Southern California
• Wendy J. Mack, University of Southern California
• Hillard Kaplan, Chapman UniversityFollow
• Andrei Irimia, University of Southern California

Document Type

Article

Publication Date

3-14-2026

Abstract

Purpose

Intracranial internal carotid artery calcification (iICAC) is a form of intracranial arteriosclerosis and is associated with an elevated risk of stroke and dementia. However, iICAC’s relationship with brain atrophy remains poorly understood. We aimed to automatically quantify iICAC morphometric characteristics and evaluate their associations with regional brain volumes (BVs).

Methods

We developed an automated approach to compute iICAC surface area and thickness from CT brain scans in a sample of physically active South American subsistence farmers (n = 1,232, age range: 40 years to 92 years, 48.1% female, 794 Tsimane and 438 Moseten). Linear regression models were used to assess associations between two iICAC features and regional BVs, adjusted for age, sex, population, and total intracranial volume.

Results

Significant negative relationships were found between regional BVs and iICAC surface area, but not iICAC thickness. Frontal, parietal, temporal, and subcortical BVs exhibited significant negative associations with iICAC surface area (standardized range: -0.146 to -0.066, p ≤ 0.013), while the occipital BV did not (standardized = -0.035, p = 0.249; = 0.007, p = 0.810). Subcortical BVs demonstrated the strongest negative associations with iICAC surface area (standardized = -0.146, p < 0.001; = -0.139, p <  0.001).

Conclusion

iICAC surface area—assumed to reflect arterial stiffness—shows a stronger relationship with regional BV loss than iICAC thickness—assumed to indicate arterial stenosis. The findings suggest that brain regions primarily supplied by the anterior circulation are more vulnerable to iICAC-related atrophy. Subcortical BVs showed the strongest negative associations with iICAC surface area, with region-specific analyses identifying significant effects in the putamen, thalamus, hippocampus, amygdala, pallidum, and ventral diencephalon, suggesting heightened vulnerability of deep gray-matter structures to iICAC-related atrophy.

Comments

This article was originally published in Neuroradiology, volume 68, in 2026. https://doi.org/10.1007/s00234-026-03918-9

Recommended Citation

Xu, X., Chaudhari, N.N., Imms, P. et al. Segmentation and morphometry of intracranial internal carotid artery calcification in relation to brain atrophy. Neuroradiology 68, 911–926 (2026). https://doi.org/10.1007/s00234-026-03918-9

Peer Reviewed

1

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.