Brain microstructural alterations on quantitative synthetic MRI and correlation with cognitive dysfunction in...

To investigate microstructural brain alterations and their relationship with cognitive dysfunction in patients with β-thalassemia major (β-TM) using quantitative synthetic MRI (SyMRI).

Ninety-six β-TM patients and 47 healthy controls (HCs) underwent brain SyMRI, Montreal Cognitive Assessment (MoCA), and Modified Mini-Mental State Examination (MMMSE). Quantitative SyMRI parameters (T1, T2, and T1/T2 ratio) were measured in gray matter (GM) and white matter (WM). Group differences were analyzed using general linear models. Pearson correlation assessed associations between SyMRI metrics, cognitive scores, and blood test results in the β-TM group. Mediation analyses were conducted using the PROCESS macro to explore indirect effects of hematological variables on cognition via regional T1 values.

Compared to HCs, β-TM patients showed significantly increased T1 values in GM regions of the default mode and frontoparietal networks, as well as WM regions (e.g., anterior corona radiata, cingulum, corpus callosum) (P < 0.001). Compared with HCs, patients with β-TM exhibited both decreased and increased T1 values across multiple GM and WM regions. Specifically, decreased T1 values were observed in frontal, cingulate, striatal, and temporal regions, as well as major WM tracts (e.g., anterior corona radiata, cingulum, superior longitudinal fasciculus), whereas increased T1 values were identified in parietal and temporal cortices and the corpus callosum (tapetum) (P < 0.001). T1 values in GM and WM were negatively correlated with cognitive scores (P < 0.05). There were negative correlations of the SyMRI quantitative parameters with cognitive scores and with blood laboratory values for white blood cell, platelet count and direct bilirubin (r = -0.270, P = 0.031; r = -0.287, P = 0.021; r = -0.263, P = 0.036, respectively). Blood test results such as the mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) were associated with cognitive function ((r = -0.257, P = 0.040; r = - 0.247, P = 0.049). No significant mediation effects were detected.

SyMRI revealed T1 alterations in GM and WM in β-TM patients, associated with cognitive impairment and hematological markers. These findings implicated the neural correlates using SyMRI and potential neuroimaging biomarker of cognitive functioning in patients with β-TM.