{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T03:45:39Z","timestamp":1772250339130,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000006","name":"Office of Naval Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Decompression sickness (DCS) during extravehicular activity in space or after diving is caused by gaseous nitrogen. The pathophysiology is still not fully understood, as mechanisms of dissolved gas uptake and bubble development are challenging to study. We aimed to develop a new method using nitrogen-13 (\n                      <jats:sup>13<\/jats:sup>\n                      N\n                      <jats:sub>2<\/jats:sub>\n                      ) gas\n                      <jats:italic>in vivo<\/jats:italic>\n                      using positron emission tomography (PET) under normobaric pressure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A single anesthetized and ventilated Sprague Dawley rat lay supine inside a PET scanner for 30 min. The rat breathed oxygen for the first 2 min, then\n                      <jats:sup>13<\/jats:sup>\n                      N\n                      <jats:sub>2<\/jats:sub>\n                      gas mixed with oxygen for 20 min, then oxygen alone for the final 8 min. Following the scan, a mixed blood sample was taken from the heart, while the brain, liver, femur and thigh muscle were removed to determine organ radioactivity using a gamma counter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The signal intensity in the PET scanner increased from baseline (0.03) to 2\u201312 min (0.68 \u00b1 0.31), and 12\u201322 min (0.88 \u00b1 0.06), before reducing slightly from 22 to 30 min (0.61 \u00b1 0.04). All organs had radioactivity when measured in the gamma counter. We confirmed that the gas decayed radioactivity in expectance with the half-life of\n                      <jats:sup>13<\/jats:sup>\n                      N\n                      <jats:sub>2<\/jats:sub>\n                      (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.9324), and that the spectroscopy peaked just over 500 keV, suggesting no additional isotopes were present.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This study successfully demonstrated a quantitative method of tracking nitrogen gas through the body both\n                      <jats:italic>in vivo<\/jats:italic>\n                      using PET and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      using a gamma counter.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2025.1556478","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T01:32:19Z","timestamp":1743471139000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Using 13N2 and PET to track in vivo nitrogen gas kinetics during normobaric conditions"],"prefix":"10.3389","volume":"16","author":[{"given":"Edward T.","family":"Ashworth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryotaro","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Vera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Lindholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1152\/japplphysiol.00859.2023","article-title":"A novel method for tracking nitrogen kinetics in vivo under hyperbaric conditions using radioactive nitrogen-13 gas and positron emission tomography","volume":"136","author":"Ashworth","year":"","journal-title":"J. Appl. Physiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0294611","DOI":"10.1371\/journal.pone.0294611","article-title":"Effects of oxygen-prebreathing on tissue nitrogenation in normobaric and hyperbaric conditions","volume":"19","author":"Ashworth","year":"","journal-title":"PLOS ONE"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1136\/bmj.326.7404.1449","article-title":"How does it work? Positron emission tomography","volume":"326","author":"Berger","year":"2003","journal-title":"Bmj"},{"key":"B4","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3357\/AMHP.4733.2017","article-title":"Venous gas emboli and ambulation at 4.3 psia","volume":"88","author":"Conkin","year":"2017","journal-title":"Aerosp. Med. Hum. Perform."},{"key":"B5","first-page":"195","article-title":"The incidence of decompression illness in 10 years of scientific diving","volume":"42","author":"Dardeau","year":"2012","journal-title":"Diving Hyperb. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2165\/00003088-200140010-00001","article-title":"The physiological kinetics of nitrogen and the prevention of decompression sickness","volume":"40","author":"Doolette","year":"2001","journal-title":"Clin. Pharmacokinet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1093\/ajcn\/71.4.885","article-title":"Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus","volume":"71","author":"Goodpaster","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"563","DOI":"10.3769\/radioisotopes.27.10_563","article-title":"Simple method for producing 13NN and 15OO by proton bombardment of aqueous phase (author's transl)","volume":"27","author":"Iwata","year":"1978","journal-title":"Radioisotopes"},{"key":"B9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1097\/01.NURSE.0000829892.40252.ad","article-title":"Decompression sickness in SCUBA divers","volume":"52","author":"Junes","year":"2022","journal-title":"Nursing"},{"key":"B10","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1053\/j.sult.2010.10.001","article-title":"Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy","volume":"31","author":"Kinahan","year":"2010","journal-title":"Semin. Ultrasound CT MR"},{"key":"B11","volume-title":"Diving physiology and decompression sickness: considerations from humans and marine animals","author":"Lang","year":"2013"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1056\/NEJMra2116554","article-title":"Decompression sickness and arterial gas embolism","volume":"386","author":"Mitchell","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/s0022-2275(20)39619-x","article-title":"Lipid composition of the normal human brain: gray matter, white matter, and myelin","volume":"6","author":"O'Brien","year":"1965","journal-title":"J. Lipid Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1152\/jappl.1979.46.6.1169","article-title":"Solubility and partition coefficients for gases in rabbit brain and blood","volume":"46","author":"Ohta","year":"1979","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc Physiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1103\/physrev.53.124","article-title":"The radiations emitted from artificially produced radioactive substances IV. Further studies on the gamma-rays from several elements","volume":"53","author":"Richardson","year":"1938","journal-title":"Phys. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1152\/japplphysiol.00840.2015","article-title":"Why predominantly neurological decompression sickness in breath-hold divers?","volume":"120","author":"Schipke","year":"2016","journal-title":"J. Appl. Physiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.3748\/wjg.v16.i16.1993","article-title":"MRI-determined fat content of human liver, pancreas and kidney","volume":"16","author":"Sijens","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1146\/annurev-bioeng-071114-040723","article-title":"Positron emission tomography: current challenges and opportunities for technological advances in clinical and preclinical imaging systems","volume":"17","author":"Vaquero","year":"2015","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"B20","first-page":"1982","article-title":"Quantification of regional ventilation-perfusion ratios with PET","volume":"44","author":"Vidal Melo","year":"2003","journal-title":"J. Nucl. Med."},{"key":"B21","first-page":"277","article-title":"Solubility of inert gases in biological fluids and tissues: a review","volume":"7","author":"Weathersby","year":"1980","journal-title":"Undersea Biomed. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1152\/jappl.1986.61.4.1534","article-title":"Nitrogen gas exchange in the human knee","volume":"61","author":"Weathersby","year":"1986","journal-title":"J. Appl. Physiology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/000456328001700101","article-title":"A practical guide to gamma-counting in radioimmunoassay: prepared on behalf of the association of clinical biochemists' scientific and technical committee and the hospital physicists' association radionuclide topic group by","volume":"17","author":"Wilde","year":"1980","journal-title":"Ann. Clin. Biochem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1186\/s12931-022-02239-8","article-title":"Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker","volume":"23","author":"Winkler","year":"2022","journal-title":"Respir. Res."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2025.1556478\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T01:32:51Z","timestamp":1743471171000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2025.1556478\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":24,"alternative-id":["10.3389\/fphys.2025.1556478"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2025.1556478","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.06.01.543280","asserted-by":"object"}]},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"article-number":"1556478"}}