The neuroimaging evaluation, while not consistently decisive, may offer valuable support along the diagnostic pathway for patients with CTX, revealing suggestive disease features. Brain MRI abnormalities include cortical and cerebellar atrophy, and T2W/FLAIR hyperintensity involving subcortical, periventricular, and cerebellar white matter, the brainstem and especially the dentate nuclei. Some patients show dentate nuclei vacuolation and calcification-like changes. Long-term follow-up typically reveals worsened condition in vacuolated baseline patients; non-vacuolated subjects remained stable clinically and neuroradiologically. The spinal cord can also be impacted in CTX, either alone or alongside brain issues. Some patients display slowly progressing myelopathy with pyramidal and dorsal column signs, milder than classic CTX. Their MRI reveals long lesions in dorsal columns. Regarding ophthalmologic signs and symptoms, aside from cataracts, CTX often includes optic neuropathy with pale optic discs. A CTX case with optic neuropathy and optic neuritis signs—like swollen disc, enhanced peripapillary retina, optic nerve with contrast agent—has been described. While conventional MRI is highly sensitive in lesion detection, it lacks insight into underlying pathology and functional impact. Non-conventional advanced imaging methods may address these shortcomings. For instance, brain atrophy in CTX has been measured, showing lower cerebral/cerebellar volumes linked to worse clinical state. Proton MR spectroscopy unveiled biochemical shifts in CTX lesioned regions, aligning with broad neuro-axonopathy and secondary mitochondrial issues. Additionally, magnetization transfer imaging and diffusion tensor imaging expose widespread brain microstructure changes beyond lesions, both collectively and individually. In summary, MRI is a crucial CTX diagnostic and monitoring tool, with typical imaging abnormalities potentially portending prognosis. Furthermore, non-conventional advanced imaging methods could deepen our grasp of intricate CTX pathological shifts, offering potent disease outcome indicators.