{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:53:56Z","timestamp":1789750436655,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":267,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Netherlands Organization for Scientific Research","doi-asserted-by":"publisher","award":["016.196.310"],"award-info":[{"award-number":["016.196.310"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pathophysiology of X-linked adrenoleukodystrophy (ALD) is not well-understood. New quantitative MRI (qMRI) sequences, such as myelin-water imaging (MWI) and multi-shell diffusion-weighted imaging (DWI), are non-invasive techniques that can investigate microstructural abnormalities in the brain. Using these techniques, this study investigated abnormal white matter of cerebral ALD (cALD) lesions and normal-appearing white matter (NAWM) in ALD and in controls. Adult participants were scanned on 3T MRI scanners. Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were measured with diffusion tensor imaging (DTI). The neurite density index (NDI) was established using neurite orientation dispersion and density imaging (NODDI). Myelin water fractions (MWF) were evaluated with multi-compartment relaxometry diffusion-informed MWI (MCR-DIMWI) and multi-echo T2-relaxation imaging with compressed sensing (METRICS). Measures were evaluated in 10 regions of interest (ROIs) in participants with and without cALD, and in controls. A total of 81 ALD participants (69% males, of whom 17 had cALD), and 21 controls were included. FA, NDI, MWFMETRICS and MWFMCR-DIMWI were significantly lower in lesions in the corpus callosum of cALD participants than in controls. FA, NDI and MWFMETRICS also significantly differentiated the NAWM of male, but not female, ALD participants from controls. FA and NDI had the largest effect sizes for males. In the NAWM, RD was increased, whereas AD was mostly unaffected. In a few NAWM regions, qMRI measures also differed between males with and without cALD. The NAWM of males with ALD contains microstructural abnormalities. Myelin and myelinated axons are impacted by ALD pathophysiology. These techniques have potential for clinical applications.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf371","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T18:11:53Z","timestamp":1758823913000},"source":"Crossref","is-referenced-by-count":5,"title":["Myelin-water imaging and multi-shell diffusion-weighted imaging in adults with adrenoleukodystrophy"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7973-2724","authenticated-orcid":false,"given":"Hemmo A F","family":"Yska","sequence":"first","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]},{"name":"Amsterdam Neuroscience, University of Amsterdam , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno D","family":"Stellingwerff","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]},{"name":"Amsterdam Neuroscience, VU University , Amsterdam ,","place":["Netherlands"]},{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D","family":"Roosendaal","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije M C","family":"Voermans","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]},{"name":"Amsterdam Neuroscience, University of Amsterdam , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-0954","authenticated-orcid":false,"given":"Marjo S","family":"van der Knaap","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]},{"name":"Amsterdam Neuroscience, VU University , Amsterdam ,","place":["Netherlands"]},{"name":"Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra J W","family":"Pouwels","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5346-8497","authenticated-orcid":false,"given":"Marc","family":"Engelen","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Center , Amsterdam ,","place":["Netherlands"]},{"name":"Amsterdam Neuroscience, University of Amsterdam , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"2025101108020086400_fcaf371-B1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1750-1172-7-51","article-title":"X-linked adrenoleukodystrophy (X-ALD): Clinical presentation and guidelines for diagnosis, follow-up and management","volume":"7","author":"Engelen","year":"2012","journal-title":"Orphanet J Rare Dis"},{"issue":"9","key":"2025101108020086400_fcaf371-B2","first-page":"1761","article-title":"Adrenoleukodystrophy: A scoring method for brain MR observations","volume":"15","author":"Loes","year":"1994","journal-title":"AJNR Am J Neuroradiol"},{"issue":"12","key":"2025101108020086400_fcaf371-B3","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1212\/WNL.27.12.1114","article-title":"Adrenomyeloneuropathy: A probable variant of adrenoleukodystrophy. 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