The response of patients with CTX to CDCA is variable, and biomarkers to evaluate treatment effects on the brain are lacking. Furthermore, it is unclear whether all children diagnosed with CTX, especially through upcoming newborn screening programs, should be treated. Indeed, some adult patients do not develop neurological dysfunction. Diffusion tensor imaging (DTI) can provide biomarkers that can reflect neurological disease onset and progression, but implementation outside of research studies has been limited due to measurements variability and data quality issues. Thanks to a recently CE-marked platform that provides standardized and calibrated DTI markers, we can track disease progression and treatment response in adult patients with metabolic leukodystrophies in clinical practice. Examples are provided for X-linked adrenoleukodystrophy (ALD) and metachromatic leukodystrophy (MLD). Our proof-of-concept study in CTX indicates that these novel neuroimaging tools may allow a better evaluation of the therapeutic benefit of existing treatments like CDCA on the nervous system. Furthermore, the detection of brain disease onset in CTX will be critical to determine when to start treatment in asymptomatic individuals with CTX, as illustrated here in presymptomatic ALD and MLD individuals.