{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:08:26Z","timestamp":1789848506557,"version":"4.0.1"},"reference-count":64,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Proton (\n                    <jats:sup>1<\/jats:sup>\n                    H) magnetic resonance spectroscopy (MRS) is a non\u2010invasive imaging technique that can be used to assess brain metabolism. Establishing reference levels of fetal brain metabolites in a translatable preclinical model is crucial for identifying subtle deviations from normal cerebral development. Herein, we developed a\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010MRS protocol for fetal sheep across three gestational periods (109\u00a0\u00b1\u00a02, 120\u00a0\u00b1\u00a05 and 139\u00a0\u00b1\u00a02 days gestation; term is 150 days gestation). Using this protocol, we established reference metabolic levels using recommended\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010MRS data analysis techniques. Objectives included adapting protocols for reliable metabolite detection despite the challenges of fetal\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010MRS, applying the protocol at multiple gestational ages, using recommended processing techniques and comparing two analysis software packages for robustness. MRI scans were performed on a 3\u00a0T Siemens clinical system (Magnetom Skyra, Siemens Healthineers, Germany) while the ewe was ventilated.\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010MRS was performed using a point\u2010resolved spectroscopy sequence at an echo time of 135\u00a0ms and a voxel size of 15\u00a0mm\u00a0\u00d7\u00a015\u00a0mm\u00a0\u00d7\u00a015\u00a0mm, gated to maternal respiration. We showed that TARQUIN metabolite level estimates had a significantly higher Cram\u00e9r\u2013Rao lower bound uncertainty compared with LCModel in\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl aspartate and choline, with differences in fit quality, while also underestimating metabolites. LCModel was then used to determine reference levels for\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl aspartate, choline, creatine and lactate across three gestational time points in late gestation. Our findings demonstrate the feasibility and reproducibility of non\u2010invasive fetal sheep brain\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010MRS. The study highlights the importance of objective criteria for accurate data interpretation, providing insights into fetal brain development and potential non\u2010invasive applications for earlier detection of poor neurodevelopmental outcomes.\n                  <\/jats:p>","DOI":"10.1113\/ep093728","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:56:01Z","timestamp":1772974561000},"page":"1597-1611","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methodological comparison of fetal brain\n                    <sup>1<\/sup>\n                    H\u2010MRS data analysis techniques and gestational age analysis using LCModel in the fetal sheep brain"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7353-1476","authenticated-orcid":false,"given":"Jordan A.","family":"Minns","sequence":"first","affiliation":[{"name":"Early Origins of Adult Health Research Group, Robinson Research Institute, School of Pharmacy and Biomedical Sciences Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-3920","authenticated-orcid":false,"given":"Jack R. T.","family":"Darby","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Robinson Research Institute, School of Pharmacy and Biomedical Sciences Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia K.","family":"Williams","sequence":"additional","affiliation":[{"name":"Preclinical, Imaging and Research Laboratories South Australian Health and Medical Research Institute  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse T.","family":"Tu","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Robinson Research Institute, School of Pharmacy and Biomedical Sciences Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Translational Medicine Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie","family":"Guo","sequence":"additional","affiliation":[{"name":"Translational Medicine Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Miller","sequence":"additional","affiliation":[{"name":"University of British Columbia  Vancouver British Columbia Canada"},{"name":"British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Macgowan","sequence":"additional","affiliation":[{"name":"Translational Medicine Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Seed","sequence":"additional","affiliation":[{"name":"Translational Medicine Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Division of Cardiology Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Paediatrics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Near","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"},{"name":"Sunnybrook Research Institute, Physical Sciences Platform Hurvitz Brain Sciences Program  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8602-8519","authenticated-orcid":false,"given":"Janna L.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Early Origins of Adult Health Research Group, Robinson Research Institute, School of Pharmacy and Biomedical Sciences Adelaide University  Adelaide South Australia Australia"},{"name":"Division of Cardiology Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Department of Physiology, Faculty of Medicine University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP089237"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738060210070101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.119602"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3196"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0740254.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs283"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4702"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1340012"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278110"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280019"},{"key":"e_1_2_10_12_1","unstructured":"Davies\u2010Jenkins C. Chandler M. Langbein F. &Shermer S.(2021).Benchmarking GABA quantification: A ground truth data set and comparative analysis of TARQUIN LCModel jMRUI and Gannet."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00273.2017"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.897ab.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4512"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmir.2017.06.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.6.29"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2005.11.021"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21017"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21017"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199909000-00005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119153"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-003-0774-5"},{"key":"e_1_2_10_25_1","first-page":"201","article-title":"MRI of normal brain maturation","volume":"7","author":"Holland B. A.","year":"1986","journal-title":"AJNR American Journal of Neuroradiology"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.10057"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2014.04.004"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.29370"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.06.005"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-5108(18)30165-9"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2016-311403"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.113.072595"},{"key":"e_1_2_10_33_1","first-page":"128","article-title":"Development and aging of the cerebrum: Assessment with proton MR spectroscopy","volume":"22","author":"Kadota T.","year":"2001","journal-title":"Ajnr American Journal of Neuroradiology"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/sp.2000.6360"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.72351"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2001.117677"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25568"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910300405"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.7589\/52.2S.S65"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.101991"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1979.tb00664.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(01)00255-3"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP286666"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2017.01.017"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2008.09.005"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117016"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910300604"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.698"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.2248"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21081"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2004.tb02692.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP281002"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26091"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.29387"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2010.03.003"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00100"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26022"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10497"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(98)70077-8"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1053\/sp.2000.6361"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/af\/vfz019"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(00)00349-X"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4482"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP093728","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP093728","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP093728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:51:51Z","timestamp":1789847511000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP093728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":64,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1113\/EP093728"],"URL":"https:\/\/doi.org\/10.1113\/ep093728","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,2]]},"assertion":[{"value":"2026-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}