Longitudinal Diffusion MRI Characterizes Persistent Perivascular Diffusivity Asymmetry and White Matter Abnormalities...

Background/Objectives: Delayed neurological deficits after decompressive craniectomy may improve after cranioplasty, but quantitative imaging markers for postoperative monitoring remain limited. This study evaluated diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as an exploratory diffusion-based marker of defect-referenced perivascular diffusivity asymmetry and examined its relationship with white matter microstructure. Methods: Forty-three adults undergoing first-time cranioplasty after decompressive craniectomy and thirty-four matched healthy controls underwent diffusion magnetic resonance imaging and neuropsychological assessment before cranioplasty; twenty-five patients were reassessed at 3 months. DTI-ALPS was quantified globally and according to defect laterality. The white matter microstructure was assessed using tract-based spatial statistics and automated fiber quantification. The associations between imaging measures and cognitive performance were also examined. Results: Global DTI-ALPS was significantly lower in patients than in controls both before cranioplasty and at 3-month follow-up, with no significant longitudinal increase. Defect-referenced hemispheric asymmetry persisted, with lower ALPS values on the affected side, and white matter abnormalities were widespread before cranioplasty and remained evident at follow-up. Associations between imaging measures and cognitive performance were not significant after multiple-comparison correction. Conclusions: DTI-ALPS may capture persistent defect-related hemispheric diffusion asymmetry after cranioplasty and provide complementary information to conventional white matter metrics. However, in patients with substantial postoperative anatomical and fiber-orientation changes, ALPS should be interpreted cautiously as an exploratory proxy of perivascular diffusivity rather than as a direct measure of glymphatic function or physiological recovery.