In Vivo Surface Reconstruction of Three Signal-defined Intracortical Layers Using 5T 3D FLAIR MR Imaging

Background : In vivo whole-cortex quantification of intracortical signal-defined layering on the routinely acquired structural MRI remains limited. Purpose : To develop and validate an automated framework to reconstruct three intracortical signal-defined layers from 5T three-dimensional (3D) T2-weighted fluid-attenuated inversion recovery (FLAIR) and to characterize whole-cortex morphometrics and regional organization across a prespecified cortical organizational framework. Materials and Methods : In this retrospective study, 5T 3D FLAIR images were acquired between February and July 2024. Brain Multi-Layer Surface Reconstruction (BrainMLSR) reconstructed three intracortical signal-defined layers, and derived intracortical layer thickness and surface area measures and ratios. Performance was evaluated against manual annotations and assessed for test-retest repeatability (n=13) and cross-site feasibility (n=2). Paired two-tailed t-tests and linear mixed-effects models were used. A proof-of-concept analysis compared Heschl's gyrus ratios between 19 patients with temporal lobe epilepsy (TLE) and 19 age-matched healthy controls (HC Results : A total of 270 healthy participants (mean age, 54.4±14.5 years; 146 men) were included. Agreement with manual hypointense-layer annotations was high (Dice, 0.960±0.003), and was similar in the cross-site dataset (Dice, 0.954±0.009). In the test-retest dataset, average symmetric surface distance was less than 0.1 mm. Across prespecified systems, thickness and surface area ratios varied by region; within an auditory-perisylvian hierarchy, banksSTS showed a localized turning point with an increased hyperintense layer thickness ratio and decreased hypointense layer thickness ratio, accompanied by inflections in surface area ratios (P < .001). In bilateral Heschl's gyrus, hypointense (left: 0.619±0.262 vs 0.881 ± 0.102; right: 0.607±0.310 vs 0.907±0.141 mm) and isointense (left: 0.406±0.225 vs 0.678± 0.128; right: 0.478±0.232 vs 0.808 ± 0.176 mm) layer thicknesses were lower in TLE than in HC (all P<.001). Conclusion : BrainMLSR enabled accurate and repeatable in vivo reconstruction of three intracortical signal-defined layers from a single 5T 3D T2-weighted FLAIR acquisition and provided whole-cortex boundary-based morphometry with interpretable regional organization. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 82441023, U23A20295, 62131015, 82394432 China Ministry of Science and Technolog, S20240085, STI2030-Major Projects-2022ZD0209000, STI2030-Major Projects-2022ZD0213100 Shanghai Municipal Central Guided Local Science and Technology Development Fund, YDZX20233100001001 The Key R&D Program of Guangdong Province, China, 2023B0303040001