Association of Baseline Glymphatic‐Related MRI Metrics With Neoadjuvant Chemotherapy‐Related Cognitive Impairment in Patients With Breast Cancer

BACKGROUND: Chemotherapy-related cognitive impairment (CRCI) is a common complication for cancer survivors. The glymphatic system is increasingly recognized as playing a role in cognitive health. However, whether the glymphatic system is associated with CRCI and its dynamic change during chemotherapy remains unclear. PURPOSE: To investigate longitudinal changes of glymphatic-related MRI metrics during chemotherapy and their association with CRCI. STUDY TYPE: Prospective longitudinal. POPULATION: Sixty two female patients with breast cancer underwent brain MRI and neuropsychological assessments at baseline and after chemotherapy. FIELD STRENGTH/SEQUENCE: Resting-state functional MRI, diffusion tensor imaging (DTI), 3D T1-weighted magnetization-prepared rapid gradient echo sequence at 3 T. ASSESSMENT: Patients were divided into cognitive decline (n = 22) and cognitive remain (n = 40) groups according to the Montreal Cognitive Assessment (MoCA) and the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale. MR metrics, including blood-oxygen-level-dependent cerebrospinal coupling (BOLD-CSF coupling), DTI along the perivascular space (DTI-ALPS) index, fraction of perivascular space (PVS/ICV), and choroid plexus volume to intracranial volume (ChP/ICV), were used to reflect glymphatic function. STATISTICAL TESTS: Linear mixed-effects models were utilized to assess longitudinal trajectories. Analysis of covariance was used to identify differences in glymphatic-related MRI metrics between groups. Multivariable linear regression was used to determine the association between post-chemotherapy cognitive decline and baseline metrics. Significance was defined as p < 0.05 or FDR corrected p < 0.05. RESULT: After chemotherapy, significant cognitive decline, an increase in PVS/ICV, ChP/ICV, and BOLD-CSF coupling strength were observed. Longitudinal changes in MRI metrics did not differ between the cognitive remain and cognitive decline groups (FDR-corrected p = 0.234-0.833). The cognitive decline group had significantly weaker baseline BOLD-CSF coupling strength and larger baseline PVS/ICV compared to the cognitive remain group. Multivariable linear regression revealed that baseline BOLD-CSF coupling strength and PVS/ICV were independent predictors for post-chemotherapy MoCA and FACT-cog scores. DATA CONCLUSION: Weaker baseline BOLD-CSF coupling strength and larger PVS volume fraction are associated with CRCI. Longitudinal changes of glymphatic-related MRI metrics may not be associated with CRCI. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.