Segmental Abnormalities of White Matter Microstructure in Primary Hypothyroidism Identified by Automated Fiber Quantification

Introduction: Hypothyroidism leads to impaired white matter (WM) integrity, associated with cognitive/neuropsychiatric dysfunction. However, the specific segmental abnormalities of the fibers remain unexplored. Therefore, this study aimed to investigate whether the damage of the WM is limited to a specific segment or the entire bundle via diffusion metrics using automated fiber quantification. Methods: A cross-sectional study was conducted on 31 hypothyroid patients and 28 healthy controls. Thyroid-related hormone levels, cognitive/neuropsychiatric function, and diffusion tensor image data were collected and analyzed. Correlation and random forest analyses were also performed. Results: The mean fractional anisotropy (FA) values were reduced at the fiber tract level. The mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased in several fiber tracts, i.e., cingulum cingulate (CC), anterior forceps of corpus callosum (CCF_A). Significant correlations were found between cognitive function and diffusion indicators such as the FA value of the left corticospinal tract and arcuate fasciculus (AF), the MD value of left CC, the RD value of left AF, the AD value of left CC, and CCF_A. The widespread microstructure disruption was spread on multiple specific segments of different tracts at the point-wise level. The random forest revealed that the accuracy of recognizing hypothyroid patients was 82.5%, with the anterior component of CCF_A having the most significant contribution. Conclusion: WM microstructural integrity impairments were found in multi-segments of the multiple fiber bundles in hypothyroidism, which might be a potential mechanism of the underlying neurocognitive decline and cerebral impairment. The CCF_A might serve as a neuro biomarker for early warning of cerebral impairment in hypothyroidism.