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Male ALD patients may present with either the severe neurological phenotype of cerebral ALD, characterized by inflammatory demyelination in the white matter and rapid neurological deterioration, or milder forms, such as adrenomyeloneuropathy. We aimed to identify early brain changes in asymptomatic ALD patients prior to the clinical onset of cerebral ALD or adrenomyeloneuropathy by exploratory analysis of multimodal MRI data. Multimodal MRI data\u2014including structural images, diffusion tensor imaging, magnetization transfer imaging and MR spectroscopy\u2014were obtained from asymptomatic ALD patients during regular follow-up MRIs. Longitudinal MRI data were analysed from 12 asymptomatic ALD patients aged 10\u201318 years who did not develop a cerebral ALD phenotype during our surveillance and from 12 healthy age-matched male controls. Volumetric analyses of brain structures were performed using structural MRI data, as well as region-of-interest measurements on diffusion tensor imaging, magnetization transfer imaging and MR spectroscopy data. Statistical analysis was performed using linear mixed-effects models. Volumetry indicated increased white matter volume in asymptomatic ALD patients. Diffusion tensor imaging analysis revealed increased values of radial and mean diffusivity in the supratentorial white matter. Magnetization transfer saturation values derived from magnetization transfer imaging metrics were increased in the cortical and subcortical grey matter, but not in the white matter. MR spectroscopy showed increased inositol levels in the frontal white matter. Our diffusion tensor imaging and MR spectroscopy data indicate early white matter pathology in adolescent asymptomatic ALD patients. Among these findings, increased white matter volume and, in addition, elevated magnetization transfer saturation values in the grey matter are novel MRI phenotypes associated with asymptomatic ALD. These results suggest that not only white matter but also grey matter can be pathologically altered even before the onset of neurological phenotypes. Multimodal MRI parameters therefore constitute promising biomarkers for the assessment of pre-symptomatic brain tissue alterations in ALD and may be useful in future clinical studies targeting early therapeutic intervention.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag311","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T20:29:16Z","timestamp":1788035356000},"source":"Crossref","is-referenced-by-count":0,"title":["Multimodal quantitative MRI finds early brain changes in asymptomatic X-linked adrenoleukodystrophy"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7931-9335","authenticated-orcid":false,"given":"Kolja","family":"Meier","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Goettingen , Goettingen 37075 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prativa","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara Maleen","family":"Marten","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irini","family":"Gkalimani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunther","family":"Helms","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Lund University , Lund 221 85 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dechent","sequence":"additional","affiliation":[{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Goettingen , Goettingen 37075 ,","place":["Germany"]},{"name":"Department of Cognitive Neurology, MR Research in Neurosciences, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Rosewich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Goettingen , Goettingen 37075 ,","place":["Germany"]},{"name":"Department of Neuropaediatrics, University Hospital Tuebingen , Tuebingen 72076 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffi","family":"Dreha-Kulaczewski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Goettingen , Goettingen 37075 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center Goettingen , Goettingen 37075 ,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Goettingen , Goettingen 37075 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