{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:36:43Z","timestamp":1792197403190,"version":"4.4.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"publisher","award":["W.OR15-10"],"award-info":[{"award-number":["W.OR15-10"]}],"id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09150161910230"],"award-info":[{"award-number":["09150161910230"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol"],"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n To evaluate changes in diaphragmatic function in Pompe disease using MRI over time, both during natural disease course and during treatment with enzyme replacement therapy (ERT).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective study, 30 adult Pompe patients and 10 healthy controls underwent pulmonary function tests and spirometry-controlled MRI twice, with an interval of 1 year. In the sagittal view of 3D gradient echo breath-hold acquisitions, diaphragmatic motion (cranial-caudal ratio between end-inspiration and end-expiration) and curvature (diaphragm height and area ratio) were calculated using a machine learning algorithm based on convolutional neural networks. Changes in outcomes after 1 year were compared between Pompe patients and healthy controls using the Mann-Whitney test.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Pulmonary function outcomes and cranial-caudal ratio in Pompe patients did not change significantly over time compared to healthy controls. Diaphragm height ratio increased by 0.04 (\u22120.38 to 1.79) in Pompe patients compared to \u22120.02 (\u22120.18 to 0.25) in healthy controls (\n p<\/jats:italic>\n = 0.02). An increased diaphragmatic curvature over time was observed in particular in untreated Pompe patients (\n p<\/jats:italic>\n = 0.03), in those receiving ERT already for over 3 years (\n p<\/jats:italic>\n = 0.03), and when severe diaphragmatic weakness was found on the initial MRI (\n p<\/jats:italic>\n = 0.01); no progression was observed in Pompe patients who started ERT less than 3 years ago and in Pompe patients with mild diaphragmatic weakness on their initial MRI.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n MRI enables to detect small changes in diaphragmatic curvature over 1-year time in Pompe patients. It also showed that once severe diaphragmatic weakness has occurred, improvement of diaphragmatic muscle function seems unlikely.<\/jats:p>\n <\/jats:sec>\n \n Key Points<\/jats:title>\n \n \u2022\n Changes in diaphragmatic curvature in Pompe patients over time assessed with 3D MRI may serve as an outcome measure to evaluate the effect of treatment on diaphragmatic function<\/jats:italic>\n .\n <\/jats:p>\n \n \u2022\n Diaphragmatic curvature showed a significant deterioration after 1 year in Pompe patients compared to healthy controls, but the curvature seems to remain stable over this period in patients who were treated with enzyme replacement therapy for less than 3 years, possibly indicating a positive effect of ERT<\/jats:italic>\n .\n <\/jats:p>\n \n \u2022\n Improvement of diaphragmatic curvature over time is rarely seen in Pompe patients once diaphragmatic motion shows severe impairment (cranial-caudal inspiratory\/expiratory ratio < 1.4)<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00330-022-08940-y","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T11:04:09Z","timestamp":1657710249000},"page":"8681-8691","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MRI changes in diaphragmatic motion and curvature in Pompe disease over time"],"prefix":"10.1007","volume":"32","author":[{"given":"Laurike","family":"Harlaar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Ciet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs","family":"van Tulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmke A.","family":"van Kooten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine A. M. E.","family":"van der Beek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Brusse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"de Bruijne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm A. W. M.","family":"Tiddens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans T.","family":"van der Ploeg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2584-3357","authenticated-orcid":false,"given":"Pieter A.","family":"van Doorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"8940_CR1","unstructured":"Reuser AJJ, Hirschhorn R, Kroos MA (2019) Pompe disease: glycogen storage disease type II, acid \u03b1-glucosidase (acid maltase) deficiency. Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA (Eds.). The online metabolic and molecular bases of inherited disease. 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N Engl J Med. 366(10):932\u2013942","journal-title":"N Engl J Med."}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-022-08940-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-022-08940-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-022-08940-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T02:25:26Z","timestamp":1669688726000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-022-08940-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":23,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["8940"],"URL":"https:\/\/doi.org\/10.1007\/s00330-022-08940-y","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]},"assertion":[{"value":"10 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The scientific guarantor of this publication is Prof. Pieter A. van Doorn, MD PhD.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors of this manuscript declare relationships with the following companies:\u2022 PC received writing grants outside the submitted work from Editamed Srl.\u2022 NAMEB received funding for research and as advisor or speaker from Sanofi-Genzyme, under agreements with Erasmus MC University Medical Center.\u2022 HAWMT received unconditional research grants outside the submitted work from Roche, Novartis, CFF, Vertex, Chiesi, Vectura, and Gilead and participated in the last 5 years in expert panels for Vertex and Gilead. All financial aspects for the grants are handled by Sophia Research BV. HAWMT is director of the Erasmus MC Lung Analysis laboratory and acts as consultant for Thirona.\u2022 ATP received funding for research and\/or clinical trials and as advisor or speaker from Amicus, Sanofi-Genzyme, Ultragenix, Spark Therapeutics, Audentes, Biomarin, Shire, Ciesi, and Sarepta under agreements with Erasmus MC University Medical Center and the relevant industry.The other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Prof. Dimitris Rizopoulos (Erasmus MC, University Medical Center Rotterdam, Department of Biostatistics) kindly provided statistical advice for this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was obtained from all subjects (patients) in this study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional Review Board approval was obtained.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"In the current prospective study, 30 Pompe patients and 10 healthy controls were included. All these participants initially participated in a cross-sectional study, in which we reported a decreased motion and an abnormal curvature of the diaphragm during inspiration in Pompe patients (Harlaar L, Ciet P, van Tulder G, et al Chest MRI to diagnose early diaphragmatic weakness in Pompe disease. Orphanet Journal of Rare Diseases<\/i>. 2021;16(1):21).In this follow-up study, we repeated the MRI study after 1 year, to evaluate possible changes in the motion and curvature of the diaphragm over time and during treatment with enzyme replacement therapy. We used 3D SPGR breath-hold acquisitions at end-expiration and end-inspiration, instead of dynamic sagittal 2D images that were used in the cross-sectional study. Therefore, we were able to compare MRI outcomes on a matching sagittal level at the initial MRI and the follow-up MRI. In addition, we developed automatic lung segmentations, while in the cross-sectional study we used manual lung segmentations.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"value":"\u2022 prospective\u2022 case-control study\u2022 performed at one institution","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}