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In addition to muscle, dystrophin is expressed in the brain in both neurons and glial cells. Previous studies have shown altered white matter microstructure in patients with DMD using diffusion tensor imaging (DTI). However, DTI measures the diffusion properties of water, a ubiquitous molecule, making it difficult to unravel the underlying pathology. Diffusion\u2010weighted spectroscopy (DWS) is a complementary technique which measures diffusion properties of cell\u2010specific intracellular metabolites. Here we performed both DWS and DTI measurements to disentangle intra\u2010 and extracellular contributions to white matter changes in patients with DMD. Scans were conducted in patients with DMD (15.5\u2009\u00b1\u20094.6\u2009y\/o) and age\u2010 and sex\u2010matched healthy controls (16.3\u2009\u00b1\u20093.3\u2009y\/o). DWS measurements were obtained in a volume of interest (VOI) positioned in the left parietal white matter. Apparent diffusion coefficients (ADCs) were calculated for total <jats:italic>N<\/jats:italic>\u2010acetylaspartate (tNAA), choline compounds (tCho), and total creatine (tCr). The tNAA\/tCr and tCho\/tCr ratios were calculated from the non\u2010diffusion\u2010weighted spectrum. Mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and fractional anisotropy of water within the VOI were extracted from DTI measurements. DWS and DTI data from patients with DMD (respectively <jats:italic>n<\/jats:italic>\u00a0=\u200920 and <jats:italic>n<\/jats:italic>\u00a0=\u200918) and <jats:italic>n<\/jats:italic>\u00a0=\u200910 healthy controls were included. No differences in metabolite ADC or in concentration ratios were found between patients with DMD and controls. In contrast, water diffusion (MD, <jats:italic>t<\/jats:italic>\u00a0=\u2009\u22122.727, <jats:italic>p<\/jats:italic>\u00a0=\u20090.011; RD, <jats:italic>t<\/jats:italic>\u00a0=\u2009\u22122.720, <jats:italic>p<\/jats:italic>\u00a0=\u20090.011; AD, <jats:italic>t<\/jats:italic>\u00a0=\u2009\u22122.715, <jats:italic>p<\/jats:italic>\u00a0=\u20090.012) within the VOI was significantly higher in patients compared with healthy controls. Taken together, our study illustrates the potential of combining DTI and DWS to gain a better understanding of microstructural changes and their association with disease mechanisms in a clinical setting.<\/jats:p>","DOI":"10.1002\/nbm.5212","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T04:15:22Z","timestamp":1721016922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Probing diffusion of water and metabolites to assess white matter microstructure in Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-3977","authenticated-orcid":false,"given":"Rosanne","family":"Govaarts","sequence":"first","affiliation":[{"name":"C.J. 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Gorter MRI Center, Department of Radiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3135-8131","authenticated-orcid":false,"given":"Kieren G.","family":"Hollingsworth","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-5143","authenticated-orcid":false,"given":"Erik H.","family":"Niks","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Duchenne Centre Netherlands  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-4895","authenticated-orcid":false,"given":"Itamar","family":"Ronen","sequence":"additional","affiliation":[{"name":"C.J. 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