{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:58:35Z","timestamp":1791824315871,"version":"4.3.4"},"reference-count":80,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"NCI","award":["1R01NS112996-01A1"],"award-info":[{"award-number":["1R01NS112996-01A1"]}]},{"DOI":"10.13039\/100004856","name":"New York State Department of Health","doi-asserted-by":"crossref","award":["DOH01-C31291GG"],"award-info":[{"award-number":["DOH01-C31291GG"]}],"id":[{"id":"10.13039\/100004856","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cycle 50 PSC-CUNY"},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"crossref","award":["1R01MH111896"],"award-info":[{"award-number":["1R01MH111896"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"crossref","award":["1R01MH111896"],"award-info":[{"award-number":["1R01MH111896"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["J. Neural Eng."],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\n                  <jats:italic>Objective<\/jats:italic>. Transcranial direct current stimulation (tDCS) generates sustained electric fields in the brain, that may be amplified when crossing capillary walls (across blood-brain barrier, BBB). Electric fields across the BBB may generate fluid flow by electroosmosis. We consider that tDCS may thus enhance interstitial fluid flow. <jats:italic>Approach<\/jats:italic>. We developed a modeling pipeline novel in both (1) spanning the mm (head), <jats:italic>\u03bc<\/jats:italic>m (capillary network), and then nm (down to BBB tight junction (TJ)) scales; and (2) coupling electric current flow to fluid current flow across these scales. Electroosmotic coupling was parametrized based on prior measures of fluid flow across isolated BBB layers. Electric field amplification across the BBB in a realistic capillary network was converted to volumetric fluid exchange. <jats:italic>Main results<\/jats:italic>. The ultrastructure of the BBB results in peak electric fields (per mA of applied current) of 32\u201363 <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                           <mml:mtext>V<\/mml:mtext>\n                        <\/mml:mrow>\n                        <mml:mrow>\n                           <mml:msup>\n                              <mml:mrow>\n                                 <mml:mtext>m<\/mml:mtext>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:mo>\u2212<\/mml:mo>\n                                 <mml:mn>1<\/mml:mn>\n                              <\/mml:mrow>\n                           <\/mml:msup>\n                        <\/mml:mrow>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn1.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula> across capillary wall and &gt;1150 <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                           <mml:mtext>V<\/mml:mtext>\n                        <\/mml:mrow>\n                        <mml:mrow>\n                           <mml:msup>\n                              <mml:mrow>\n                                 <mml:mtext>m<\/mml:mtext>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:mo>\u2212<\/mml:mo>\n                                 <mml:mn>1<\/mml:mn>\n                              <\/mml:mrow>\n                           <\/mml:msup>\n                        <\/mml:mrow>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn2.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula> in TJs (contrasted with 0.3 <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                           <mml:mtext>V<\/mml:mtext>\n                        <\/mml:mrow>\n                        <mml:mrow>\n                           <mml:msup>\n                              <mml:mrow>\n                                 <mml:mtext>m<\/mml:mtext>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:mo>\u2212<\/mml:mo>\n                                 <mml:mn>1<\/mml:mn>\n                              <\/mml:mrow>\n                           <\/mml:msup>\n                        <\/mml:mrow>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn3.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula> in parenchyma). Based on an electroosmotic coupling of 1.0 \u00d7 10<jats:sup>\u22129<\/jats:sup> \u2013 5.6 \u00d7 10<jats:sup>\u221210<\/jats:sup>\n                  <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mfrac>\n                           <mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>m<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mtext>3<\/mml:mtext>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>s<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mo>\u2212<\/mml:mo>\n                                       <mml:mn>1<\/mml:mn>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                           <\/mml:mrow>\n                           <mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>m<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mtext>2<\/mml:mtext>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                           <\/mml:mrow>\n                        <\/mml:mfrac>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn4.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula> per <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                           <mml:mtext>V<\/mml:mtext>\n                        <\/mml:mrow>\n                        <mml:mrow>\n                           <mml:msup>\n                              <mml:mrow>\n                                 <mml:mtext>m<\/mml:mtext>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:mo>\u2212<\/mml:mo>\n                                 <mml:mn>1<\/mml:mn>\n                              <\/mml:mrow>\n                           <\/mml:msup>\n                        <\/mml:mrow>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn5.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula>, peak water fluxes across the BBB are 2.44 \u00d7 10<jats:sup>\u221210<\/jats:sup> \u2013 6.94 \u00d7 10<jats:sup>\u221210<\/jats:sup>\n                  <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mfrac>\n                           <mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>m<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mtext>3<\/mml:mtext>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>s<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mo>\u2212<\/mml:mo>\n                                       <mml:mn>1<\/mml:mn>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                           <\/mml:mrow>\n                           <mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>m<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mtext>2<\/mml:mtext>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                           <\/mml:mrow>\n                        <\/mml:mfrac>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn6.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula>, with a peak 1.5 \u00d7 10<jats:sup>\u22124<\/jats:sup> \u2013 5.6 \u00d7 10<jats:sup>\u22124<\/jats:sup>\n                  <jats:inline-formula>\n                     <jats:tex-math\/>\n                     <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mfrac>\n                           <mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>m<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mtext>3<\/mml:mtext>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:mtext>mi<\/mml:mtext>\n                              <\/mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>n<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mo>\u2212<\/mml:mo>\n                                       <mml:mn>1<\/mml:mn>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                           <\/mml:mrow>\n                           <mml:mrow>\n                              <mml:mrow>\n                                 <mml:msup>\n                                    <mml:mrow>\n                                       <mml:mtext>m<\/mml:mtext>\n                                    <\/mml:mrow>\n                                    <mml:mrow>\n                                       <mml:mtext>3<\/mml:mtext>\n                                    <\/mml:mrow>\n                                 <\/mml:msup>\n                              <\/mml:mrow>\n                           <\/mml:mrow>\n                        <\/mml:mfrac>\n                     <\/mml:math>\n                     <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"jneace4f4ieqn7.gif\" xlink:type=\"simple\"\/>\n                  <\/jats:inline-formula> interstitial water exchange (per mA). <jats:italic>Significance<\/jats:italic>. Using this pipeline, the fluid exchange rate per each brain voxel can be predicted for any tDCS dose (electrode montage, current) or anatomy. Under experimentally constrained tissue properties, we predicted tDCS produces a fluid exchange rate comparable to endogenous flow, so doubling fluid exchange with further local flow rate hot spots (\u2018jets\u2019). The validation and implication of such tDCS brain \u2018flushing\u2019 is important to establish.<\/jats:p>","DOI":"10.1088\/1741-2552\/ace4f4","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T22:31:08Z","timestamp":1688682668000},"page":"046014","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Multi-scale multi-physics model of brain interstitial water flux by transcranial Direct Current Stimulation"],"prefix":"10.1088","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4930-5214","authenticated-orcid":true,"given":"Niranjan","family":"Khadka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Poon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limary M","family":"Cancel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Tarbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marom","family":"Bikson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"jneace4f4bib1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1113\/jphysiol.2003.058255","article-title":"Oncotic pressures opposing filtration across non-fenestrated rat microvessels","volume":"557","author":"Adamson","year":"2004","journal-title":"J. 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