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The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements\u00a0of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural\u00a0alterations of\u00a0the ONSAS, from first principles, with supercomputers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Large-scale\n                      <jats:italic>in-silico<\/jats:italic>\n                      investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625\u00a0\u03bcm\/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A physiological flow speed of 0.5\u00a0mm\/s is achieved by imposing a hydrostatic pressure gradient of 0.37\u20130.67\u00a0Pa\/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover,\u00a0ONSAS trabeculae seem key players in mass transfer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present analysis suggests that a pressure drop of 0.1\u20130.2\u00a0mmHg over 4\u00a0cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12987-024-00518-8","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T07:02:14Z","timestamp":1709103734000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Large-scale in-silico analysis of CSF dynamics within the subarachnoid space of the optic nerve"],"prefix":"10.1186","volume":"21","author":[{"given":"Diego","family":"Rossinelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Fourestey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanspeter Esriel","family":"Killer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Neutzner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Iaccarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Remonda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatta","family":"Berberat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"issue":"4","key":"518_CR1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1097\/00041327-199912000-00002","volume":"19","author":"H Killer","year":"1999","unstructured":"Killer H, Laeng HR, Groscurth P. 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