{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:06:11Z","timestamp":1791824771643,"version":"4.3.4"},"posted":{"date-parts":[[2025,10,21]]},"group-title":"Neuroscience","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["RSCH25-253"],"award-info":[{"award-number":["RSCH25-253"]}],"id":[{"id":"https:\/\/ror.org\/00rj4x019","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["T32-EB021955"],"award-info":[{"award-number":["T32-EB021955"]}]},{"name":"National Institute of Health","award":["S10OD026913"],"award-info":[{"award-number":["S10OD026913"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cerebrospinal fluid (CSF) production is central to brain homeostasis, yet existing measurement techniques are invasive, technically demanding, and confounded by intracranial perturbations. Here, we introduce indirect deuterium displacement exchange imaging (CSF-iDDxI), a noninvasive MRI approach for mapping CSF production\n                  <jats:italic>in vivo<\/jats:italic>\n                  . The method leverages intravenously infused deuterium oxide (D2O), which crosses the blood\u2013CSF barrier, replaces existing H2O in CSF, producing concentration-dependent attenuation of proton (\n                  <jats:sup>1<\/jats:sup>\n                  H) signal within CSF spaces. Using high-resolution 3D balanced steady-state free precession MRI in rats, we demonstrate robust and spatially widespread D2O-induced CSF signal loss that is selectively suppressed by acetazolamide, a carbonic anhydrase inhibitor known to suppress CSF production by the choroid plexus. Dynamic imaging during intravenous D2O infusion further revealed that cortical parenchymal signal changes were unaffected by acetazolamide, confirming specificity to CSF production. Exploratory kinetic modeling estimated rapid CSF water turnover (k \u2248 0.09 min\n                  <jats:sup>-1<\/jats:sup>\n                  ) under physiological conditions, reduced to k \u2248 0.031 min\n                  <jats:sup>-1<\/jats:sup>\n                  with acetazolamide suppression, consistent with prior isotope tracer studies. Together, these findings establish CSF-iDDxI as a sensitive, pharmacologically validated tool for quantifying CSF production and turnover.\n                <\/jats:p>","DOI":"10.1101\/2025.10.20.683579","type":"posted-content","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T04:45:18Z","timestamp":1761108318000},"source":"Crossref","is-referenced-by-count":3,"title":["Indirect Deuterium Displacement Exchange Imaging for Non-invasive High-Resolution CSF Production Mapping"],"prefix":"10.64898","author":[{"given":"Debolina","family":"De","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helia","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliakbar","family":"Daemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel R.","family":"Garbow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Quirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Strahle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6983-0641","authenticated-orcid":false,"given":"Arash","family":"Nazeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025102420400528000_2025.10.20.683579v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2020"},{"key":"2025102420400528000_2025.10.20.683579v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3921"},{"key":"2025102420400528000_2025.10.20.683579v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00365-5"},{"key":"2025102420400528000_2025.10.20.683579v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241224"},{"key":"2025102420400528000_2025.10.20.683579v1.5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neuroscience.2017.04.025","article-title":"Role of choroid plexus in cerebrospinal fluid hydrodynamics","volume":"354","year":"2017","journal-title":"Neuroscience"},{"key":"2025102420400528000_2025.10.20.683579v1.6","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00004.2013"},{"key":"2025102420400528000_2025.10.20.683579v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2010.04.006"},{"key":"2025102420400528000_2025.10.20.683579v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4361"},{"key":"2025102420400528000_2025.10.20.683579v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-021-00303-x"},{"key":"2025102420400528000_2025.10.20.683579v1.10","first-page":"1","article-title":"Targeting modulation of the choroid plexus blood-CSF barrier and CSF hypersecretion via lipid nanoparticle-mediated co-delivery of siRNA and resveratrol","volume":"16","year":"2025","journal-title":"Nature Communications 2025 16:1"},{"key":"2025102420400528000_2025.10.20.683579v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.01.017"},{"key":"2025102420400528000_2025.10.20.683579v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-9-1"},{"key":"2025102420400528000_2025.10.20.683579v1.13","doi-asserted-by":"crossref","first-page":"108524","DOI":"10.1016\/j.celrep.2020.108524","article-title":"Direct Measurement of Cerebrospinal Fluid Production in Mice","volume":"33","year":"2020","journal-title":"Cell Rep"},{"key":"2025102420400528000_2025.10.20.683579v1.14","first-page":"1","article-title":"Involvement of the choroid plexus in Alzheimer\u2019s disease pathophysiology: findings from mouse and human proteomic studies","volume":"21","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"2025102420400528000_2025.10.20.683579v1.15","doi-asserted-by":"crossref","unstructured":"Nedergaard M , Goldman SA . 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