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Creatine (Cr) supplementation has been suggested as a pathophysiology-targeted treatment strategy; however, clinical outcomes remain inconsistent despite encouraging preclinical findings. The lack of methods to measure Cr distribution in the human brain may hinder the investigation. This study utilized a novel neuroimaging technique, guanidino chemical exchange saturation transfer (GuanCEST) MRI, to assess regional Cr levels in patients with PD (PwPD) and healthy controls (HCs). Twenty-five patients with PD and 24 age- and sex-matched HCs were enrolled. GuanCEST values in the caudate nucleus were significantly lower in PwPD (1.67\u2009\u00b1\u20090.26%) than HCs (1.82\u2009\u00b1\u20090.16%),\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.023. Moreover, GuanCEST signal reductions correlated with increasing PD severity, particularly in thalamic subregions. Kendall\u2019s correlation revealed a significant negative correlation between GuanCEST values in the internal medullary lamina and MDS-UPDRS-III scores (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u22120.44,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03). Regional ANCOVA further indicated that GuanCEST values in this region decreased by approximately 0.01% per unit increase in MDS-UPDRS-III (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007), adjusted for age and sex. These findings highlight GuanCEST MRI\u2019s potential as a noninvasive biomarker of Cr metabolism in PD, offering insights into disease mechanisms, therapeutic optimization, and clinical trial designs.\n                  <\/jats:p>","DOI":"10.1038\/s41531-025-01203-9","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T09:36:14Z","timestamp":1765618574000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Creatine-weighted imaging in patients with Parkinson\u2019s disease"],"prefix":"10.1038","volume":"11","author":[{"given":"Kexin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirbhay Narayan","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted M.","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"van Zijl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly A.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiadi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jannik","family":"Prasuhn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"1203_CR1","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem, B. 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