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In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO<jats:sub>2<\/jats:sub>], [Hb]), oxygen saturation (StO<jats:sub>2<\/jats:sub>) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8\u201311\u00a0kg; n\u2009=\u200952) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (&lt;\u200910\u00a0min), were assessed by the weighted Youden index (J<jats:sub>w<\/jats:sub>, w\u2009=\u20090.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48\/52 animals; 37\/48 achieved ROSC. Changes in scattering coefficient (785\u00a0nm), [HbO<jats:sub>2<\/jats:sub>], StO<jats:sub>2<\/jats:sub> and THC from baseline were significantly different in ROSC versus No-ROSC subjects (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) after 10\u00a0min of CPR. Change in [HbO<jats:sub>2<\/jats:sub>] of\u2009+\u20091.3\u00a0\u00b5mol\/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, <jats:italic>early<\/jats:italic> ROSC prediction from the third minute of CPR.<\/jats:p>","DOI":"10.1038\/s41598-021-83270-5","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T14:31:41Z","timestamp":1613572301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Non-invasive diffuse optical neuromonitoring during cardiopulmonary resuscitation predicts return of spontaneous circulation"],"prefix":"10.1038","volume":"11","author":[{"given":"Tiffany S.","family":"Ko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantine D.","family":"Mavroudis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan W.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley B.","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra M.","family":"Marquez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy W.","family":"Boorady","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahima","family":"Devarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna L.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William P.","family":"Landis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kobina","family":"Mensah-Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinay M.","family":"Nadkarni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun G.","family":"Yodh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Licht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wensheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd J.","family":"Kilbaugh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"issue":"3","key":"83270_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/MCC.0000000000000499","volume":"24","author":"AM Marquez","year":"2018","unstructured":"Marquez, A. 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