Patient-Specific Multiscale Modelling of Glioblastoma: Targeted Modulation of Interstitial Fluid Flow Using Electric Field

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Abstract Glioblastomas are aggressive, highly heterogeneous brain tumours with poor prognosis and limited treatment options. Their complex microenvironment, characterised by elevated interstitial fluid pressure (IFP) and irregular microstructure, presents major barriers to effective therapeutic delivery. We present a novel, patient-specific, multiscale computational model that integrates electric field modulation into the simulation of interstitial fluid dynamics in glioblastoma. Using MRI-derived brain geometries and histology informed microstructures, we simulate spatial distributions of pressure, velocity, and electric field across key tissue compartments: necrotic core, tumour, peritumoral edema, and white matter, each assigned distinct dielectric and hydraulic properties. Through asymptotic homogenisation, we derive effective transport properties that bridge macroscale anatomy with microscale heterogeneity. We solve homogenised Darcy and Laplace-type equations and compute physiologically relevant interstitial pressure and flow fields. Our simulations show elevated pressure and outward flow in tumour and edema regions. Regions of highest interstitial fluid velocity (IFV) correlated with areas of tumour progression on follow-up imaging, suggesting a mechanistic link between IFV and glioblastoma invasion, and its potential use as a predictive biomarker. We demonstrate that applying an external electric field reverses this flow, promoting inward transport and potentially improving drug uptake, offering a new strategy for targeted drug delivery. To our knowledge, this is the first model that combines patient-specific geometry and multiscale physics in the context of electric field-driven glioblastoma treatment, establishing a new computational framework for personalised therapy planning.
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Patient-Specific Multiscale Modelling of Glioblastoma: Targeted Modulation of Interstitial Fluid Flow Using Electric Field | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Patient-Specific Multiscale Modelling of Glioblastoma: Targeted Modulation of Interstitial Fluid Flow Using Electric Field Zita Borbala Fulop, Adam Domonkos Tarnoki, David Laszlo Tarnoki, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8790032/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Glioblastomas are aggressive, highly heterogeneous brain tumours with poor prognosis and limited treatment options. Their complex microenvironment, characterised by elevated interstitial fluid pressure (IFP) and irregular microstructure, presents major barriers to effective therapeutic delivery. We present a novel, patient-specific, multiscale computational model that integrates electric field modulation into the simulation of interstitial fluid dynamics in glioblastoma. Using MRI-derived brain geometries and histology informed microstructures, we simulate spatial distributions of pressure, velocity, and electric field across key tissue compartments: necrotic core, tumour, peritumoral edema, and white matter, each assigned distinct dielectric and hydraulic properties. Through asymptotic homogenisation, we derive effective transport properties that bridge macroscale anatomy with microscale heterogeneity. We solve homogenised Darcy and Laplace-type equations and compute physiologically relevant interstitial pressure and flow fields. Our simulations show elevated pressure and outward flow in tumour and edema regions. Regions of highest interstitial fluid velocity (IFV) correlated with areas of tumour progression on follow-up imaging, suggesting a mechanistic link between IFV and glioblastoma invasion, and its potential use as a predictive biomarker. We demonstrate that applying an external electric field reverses this flow, promoting inward transport and potentially improving drug uptake, offering a new strategy for targeted drug delivery. To our knowledge, this is the first model that combines patient-specific geometry and multiscale physics in the context of electric field-driven glioblastoma treatment, establishing a new computational framework for personalised therapy planning. Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Physical sciences/Engineering Physical sciences/Mathematics and computing Health sciences/Oncology Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Feb, 2026 Editor assigned by journal 09 Feb, 2026 Submission checks completed at journal 09 Feb, 2026 First submitted to journal 04 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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