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Therapeutic hypothermia (TH), which is standard of care for HIE, mitigates brain injury by suppressing anaerobic metabolism. However, more than 40% of HIE neonates have a poor outcome, even after TH. This study aims to provide metabolic biomarkers for predicting the outcomes of hypoxia\u2010ischemia (HI) after TH using hyperpolarized [1\u2010<jats:sup>13<\/jats:sup>C] pyruvate magnetic resonance spectroscopy. Postnatal day 10 (P10) mice with HI underwent TH at 1\u2009h and were scanned at 6\u20138\u2009h (P10), 24\u2009h (P11), 7\u2009days (P17), and 21\u2009days (P31) post\u2010HI on a 14.1\u2010T NMR spectrometer. The metabolic images were collected, and the conversion rate from pyruvate to lactate and the ratio of lactate to pyruvate in the injured left hemisphere (k<jats:sub>PL(L)<\/jats:sub> and Lac\/Pyr<jats:sub>(L)<\/jats:sub>, respectively) were calculated at each timepoint. The outcomes of TH were determined by the assessments of brain injury on T2\u2010weighted images and behavioral tests at later timepoint. k<jats:sub>PL(L)<\/jats:sub> and Lac\/Pyr<jats:sub>(L)<\/jats:sub> over time between the good\u2010outcome and poor\u2010outcome groups and across timepoints within groups were analyzed. We found significant differences in temporal trends of k<jats:sub>PL(L)<\/jats:sub> and Lac\/Pyr<jats:sub>(L)<\/jats:sub> between groups. In the good\u2010outcome group, k<jats:sub>PL(L)<\/jats:sub> increased until P31 with a significantly higher value at P31 compared with that at P10, while the level of Lac\/Pyr<jats:sub>(L)<\/jats:sub> at P31 was notably higher than those at all other timepoints. In the poor\u2010outcome group, k<jats:sub>PL(L)<\/jats:sub> and Lac\/Pyr<jats:sub>(L)<\/jats:sub> increased within 24\u2009h. The k<jats:sub>PL(L)<\/jats:sub> value at P11 was considerably higher compared with P10. Discrete temporal changes of k<jats:sub>PL(L)<\/jats:sub> and Lac\/Pyr<jats:sub>(L)<\/jats:sub> after TH between the good\u2010outcome and poor\u2010outcome groups were seen as early as 24\u2009h after HI, reflecting various TH effects on brain anaerobic metabolism, which may provide insights for early screening for response to TH.<\/jats:p>","DOI":"10.1002\/nbm.5196","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T04:54:50Z","timestamp":1717995290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Brain metabolism after therapeutic hypothermia for murine hypoxia\u2010ischemia using hyperpolarized [1\u2010<sup>13<\/sup>C] pyruvate magnetic resonance spectroscopy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-9086","authenticated-orcid":false,"given":"Xiaodan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of 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