{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:20:36Z","timestamp":1765484436122,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pelizaeus\u2010Merzbacher disease (PMD) is a rare childhood hypomyelinating leukodystrophy. Quantification of the pronounced myelin deficit and delineation of subtle myelination processes are of high clinical interest. Quantitative magnetic resonance imaging (qMRI) techniques can provide in vivo insights into myelination status, its spatial distribution, and dynamics during brain maturation. They may serve as potential biomarkers to assess the efficacy of myelin\u2010modulating therapies. However, registration techniques for image quantification and statistical comparison of affected pediatric brains, especially those of low or deviant image tissue contrast, with healthy controls are not yet established. This study aimed first to develop and compare postprocessing pipelines for atlas\u2010based quantification of qMRI data in pediatric patients with PMD and evaluate their registration accuracy. Second, to apply an optimized pipeline to investigate spatial myelin deficiency using myelin water imaging (MWI) data from patients with PMD and healthy controls. This retrospective single\u2010center study included five patients with PMD (mean age, 6\u2009years\u2009\u00b1\u20093.8) who underwent conventional brain MRI and diffusion tensor imaging (DTI), with MWI data available for a subset of patients. Three methods of registering PMD images to a pediatric template were investigated. These were based on (a) T1\u2010weighted (T1w) images, (b) fractional anisotropy (FA) maps, and (c) a combination of T1w, T2\u2010weighted, and FA images in a multimodal approach. Registration accuracy was determined by visual inspection and calculated using the structural similarity index method (SSIM). SSIM values for the registration approaches were compared using a <jats:italic>t<\/jats:italic> test. Myelin water fraction (MWF) was quantified from MWI data as an assessment of relative myelination. Mean MWF was obtained from two PMDs (mean age, 3.1\u2009years\u2009\u00b1\u20090.3) within four major white matter (WM) pathways of a pediatric atlas and compared to seven healthy controls (mean age, 3\u2009years\u2009\u00b1\u20090.2) using a Mann\u2013Whitney <jats:italic>U<\/jats:italic> test. Our results show that visual registration accuracy estimation and computed SSIM were highest for FA\u2010based registration, followed by multimodal, and T1w\u2010based registration (SSIM<jats:sub>FA<\/jats:sub>\u2009=\u20090.67\u2009\u00b1\u20090.04 vs. SSIM<jats:sub>multimodal<\/jats:sub>\u2009=\u20090.60\u2009\u00b1\u20090.03 vs. SSIM<jats:sub>T1<\/jats:sub>\u2009=\u20090.40\u2009\u00b1\u20090.14). Mean MWF of patients with PMD within the WM pathways was significantly lower than in healthy controls MWF<jats:sub>PMD<\/jats:sub>\u2009=\u20090.0267\u2009\u00b1\u20090.021 vs. MWF<jats:sub>controls<\/jats:sub>\u2009=\u20090.1299\u2009\u00b1\u20090.039. Specifically, MWF was measurable in brain structures known to be myelinated at birth (brainstem) or postnatally (projection fibers) but was scarcely detectable in other brain regions (commissural and association fibers). Taken together, our results indicate that registration accuracy was highest with an FA\u2010based registration pipeline, providing an alternative to conventional T1w\u2010based registration approaches in the case of hypomyelinating leukodystrophies missing normative intrinsic tissue contrasts. The applied atlas\u2010based analysis of MWF data revealed that the extent of spatial myelin deficiency in patients with PMD was most pronounced in commissural and association and to a lesser degree in brainstem and projection pathways.<\/jats:p>","DOI":"10.1002\/hbm.70014","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T11:50:53Z","timestamp":1725450653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Atlas\u2010based assessment of hypomyelination: Quantitative <scp>MRI<\/scp> in Pelizaeus\u2010Merzbacher disease"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-0998","authenticated-orcid":false,"given":"Caroline","family":"K\u00f6hler","sequence":"first","affiliation":[{"name":"Institute of Diagnostic and Interventional Neuroradiology, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1838-2230","authenticated-orcid":false,"given":"Paul","family":"Kuntke","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Neuroradiology, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prativa","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4897-1119","authenticated-orcid":false,"given":"Hannes","family":"Wahl","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Neuroradiology, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-6328","authenticated-orcid":false,"given":"Sean C. L.","family":"Deoni","sequence":"additional","affiliation":[{"name":"Advanced Baby Imaging Lab, School of Engineering Brown University  Providence Rhode Island USA"},{"name":"Maternal, Newborn, and Child Health Discovery and Tools Bill and Melinda Gates Foundation  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutta","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffi","family":"Dreha\u2010Kulaczewski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagen H.","family":"Kitzler","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Neuroradiology, Faculty of Medicine and University Hospital Carl Gustav Carus Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynirp.2022.100120"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.09.025"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/JMRI.21130"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25108"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.07.037"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/MRM.24429"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21704"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6182-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380401900504"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2011.00013"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/JNR.20742"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.06.009"},{"key":"e_1_2_10_14_1","first-page":"4516","volume-title":"Proceedings of the 18th meeting of the international society for magnetic resonance in medicine","author":"Hurley S. A.","year":"2010"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.9.747"},{"issue":"1","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.23967\/j.rimni.2019.03.004","article-title":"Efficient combined SSIM\u2010 and landmark\u2010driven image registration in a variational framework","volume":"35","author":"Larrey\u2010Ruiz J.","year":"2019","journal-title":"Revista Internacional de M\u00e9todos Num\u00e9ricos Para C\u00e1lculo y Dise\u00f1o en Ingenier\u00eda"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.05.028"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23458"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2013.08.030"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2005.12.037"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738231152658"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/app12083754"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.01.051"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24194"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROIMAGE.2012.06.064"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13025"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1109\/IPTA.2008.4743741"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000343049.00540.c8"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00401-009-0562-8"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1267"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2023.103427"},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","unstructured":"IEEE Transactions on Image Processing 2004 13 Image quality assessment: From error visibility to structural similarity","DOI":"10.1109\/TIP.2003.819861"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh409"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.07.033"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.70014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T10:29:59Z","timestamp":1726223399000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.70014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":33,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/hbm.70014"],"URL":"https:\/\/doi.org\/10.1002\/hbm.70014","archive":["Portico"],"relation":{},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"type":"print","value":"1065-9471"},{"type":"electronic","value":"1097-0193"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2024-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70014"}}