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Unlike diffusion\u2010weighted MRI (dMRI), diffusion\u2010weighted MR spectroscopy (dMRS) can assess cell\u2010type specific microstructural changes, providing indirect information on both cell composition and microstructure through the quantification and interpretation of metabolites' diffusion properties. This work investigates age\u2010related changes in the higher\u2010order diffusion properties of total N\u2010Acetyl\u2010aspartate (neuronal biomarker), total choline (glial biomarker), and total creatine (both neuronal and glial biomarker) beyond the classical apparent diffusion coefficient in cerebral and cerebellar gray matter of healthy human brain. Twenty\u2010five subjects were recruited and scanned using a diffusion\u2010weighted semi\u2010LASER sequence in two brain regions\u2010of\u2010interest (ROI) at 3T: posterior\u2010cingulate (PCC) and cerebellar cortices. Metabolites' diffusion was characterized by quantifying metrics from both Gaussian and non\u2010Gaussian signal representations and biophysical models. All studied metabolites exhibited lower apparent diffusivities and higher apparent kurtosis values in the cerebellum compared to the PCC, likely stemming from the higher microstructural complexity of cellular composition in the cerebellum. Multivariate regression analysis (accounting for ROI tissue composition as a covariate) showed slight decrease (or no change) of all metabolites' diffusivities and slight increase of all metabolites' kurtosis with age, none of which statistically significant (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). The proposed age\u2010trajectories provide benchmarks for identifying anomalies in the diffusion properties of major brain metabolites which could be related to pathological mechanisms altering both the brain microstructure and cellular composition.<\/jats:p>","DOI":"10.1111\/acel.14477","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T07:42:47Z","timestamp":1737013367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Age\u2010Trajectories of Higher\u2010Order Diffusion Properties of Major Brain Metabolites in Cerebral and Cerebellar Gray Matter Using In\u00a0Vivo Diffusion\u2010Weighted <scp>MR<\/scp> Spectroscopy at 3T"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-7395","authenticated-orcid":false,"given":"Kadir","family":"\u015eim\u015fek","sequence":"first","affiliation":[{"name":"Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology Cardiff University  Cardiff UK"},{"name":"School of Computer Science and Informatics Cardiff University  Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Gallea","sequence":"additional","affiliation":[{"name":"Paris Brain Institute \u2013 ICM Team \u201cMovement Investigations and Therapeutics\u201d  Paris France"},{"name":"Paris Brain Institute \u2013 ICM, INSERM U 1127, CNRS UMR 7225 Sorbonne University  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guglielmo","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Neuromedicine and Movement Science Norwegian University of Science and Technology  Trondheim Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Leh\u00e9ricy","sequence":"additional","affiliation":[{"name":"Paris Brain Institute \u2013 ICM Team \u201cMovement Investigations and Therapeutics\u201d  Paris France"},{"name":"Paris Brain Institute \u2013 ICM, INSERM U 1127, CNRS UMR 7225 Sorbonne University  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Branzoli","sequence":"additional","affiliation":[{"name":"Paris Brain Institute \u2013 ICM, INSERM U 1127, CNRS UMR 7225 Sorbonne University  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Palombo","sequence":"additional","affiliation":[{"name":"Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology Cardiff University  Cardiff UK"},{"name":"School of Computer Science and Informatics Cardiff University  Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/NBM.3841"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/CNE.10884"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12311\u2010023\u201001577\u20107"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.1997.1313"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNAGI.2021.682109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12311\u2010013\u20100481\u2010Z\/FIGURES\/7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROBIOLAGING.2016.07.022"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3085"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3481"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511666469.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/JNR.10121"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBI.2021.10.005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/MRM.26969"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROBIOLAGING.2020.07.017"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27222"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116075"},{"key":"e_1_2_10_18_1","unstructured":"D\u00f6ring A. 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