{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/118979"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/118979","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Examining location-specific invasive patterns: linking interstitial fluid and vasculature in glioblastoma","abstract":"Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing perfusion-based imaging protocols. Using this method, we examined transport associated with invasion in a murine GL261 cell line. We found that elevated interstitial fluid velocity magnitudes, decreased diffusion coefficients and regions with accumulating flow were significantly associated with invasion. We tested the validity of our invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions indicating location-specific structures may drive both interstitial flow and corresponding invasion heterogeneities. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Over-expression of VEGF-C in the tumor microenvironment neither enhanced drainage nor altered invasion in comparison to our control, indicating other tumor-secreted growth factors, such as VEGF-A, may play a larger role in mediating flow and invasion. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease.","abstract_html":"Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing perfusion-based imaging protocols. Using this method, we examined transport associated with invasion in a murine GL261 cell line. We found that elevated interstitial fluid velocity magnitudes, decreased diffusion coefficients and regions with accumulating flow were significantly associated with invasion. We tested the validity of our invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions indicating location-specific structures may drive both interstitial flow and corresponding invasion heterogeneities. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Over-expression of VEGF-C in the tumor microenvironment neither enhanced drainage nor altered invasion in comparison to our control, indicating other tumor-secreted growth factors, such as VEGF-A, may play a larger role in mediating flow and invasion. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease.","abstract_has_math":false,"creators":["Esparza, Cora Marie"],"institution":"Virginia Tech","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Biomedical Engineering","degree_department":"Department of Biomedical Engineering and Mechanics","school":null,"contributors":[],"advisors":[],"committee_chairs":["Munson, Jennifer M."],"committee_members":["Wang, Maosen","Theus, Michelle H.","Vlaisavljevich, Eli","Chappell, John Christopher"],"year":2024,"date_issued":"2024-05-14","date_published":"2024-05-14","updated_at":"2026-07-22T22:19:15Z","subjects":["interstitial fluid flow","glioblastoma","DCE-MRI","invasion","transport","vasculature"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:39791"],"render_values":[{"text":"vt_gsexam:39791","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10919/118979","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Munson, Jennifer M."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Wang, Maosen","Theus, Michelle H.","Vlaisavljevich, Eli","Chappell, John Christopher"]},{"key":"dc:contributor.department","label":"Department","values":["Department of Biomedical Engineering and Mechanics"]},{"key":"dc:creator","label":"Author","values":["Esparza, Cora Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-05-15T08:01:15Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-05-15T08:01:15Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-05-14"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["interstitial fluid flow","glioblastoma","DCE-MRI","invasion","transport","vasculature"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:39791"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10919/118979"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing perfusion-based imaging protocols. Using this method, we examined transport associated with invasion in a murine GL261 cell line. We found that elevated interstitial fluid velocity magnitudes, decreased diffusion coefficients and regions with accumulating flow were significantly associated with invasion. We tested the validity of our invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions indicating location-specific structures may drive both interstitial flow and corresponding invasion heterogeneities. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Over-expression of VEGF-C in the tumor microenvironment neither enhanced drainage nor altered invasion in comparison to our control, indicating other tumor-secreted growth factors, such as VEGF-A, may play a larger role in mediating flow and invasion. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing imaging projects. Using this method, we examined transport associated with cancer cell invasion in a mouse tumor cell line. We found that interstitial fluid speeds were elevated while diffusion was decreased in regions of invasion. Further, regions that had interstitial fluid flow congregation were significantly associated with invasion. We tested the validity of these invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions, indicating location-specific structures may drive both interstitial flow and invasion differences. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Following administration of a meningeal lymphatic-relevant protein, we saw no changes in flow or invasion in comparison to our untreated control, indicating other tumor-secreted proteins may play a larger role in these responses. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:title","label":"Title","values":["Examining location-specific invasive patterns: linking interstitial fluid and vasculature in glioblastoma"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Munson, Jennifer M."],"dc:contributor.committeemember":["Wang, Maosen","Theus, Michelle H.","Vlaisavljevich, Eli","Chappell, John Christopher"],"dc:contributor.department":["Department of Biomedical Engineering and Mechanics"],"dc:creator":["Esparza, Cora Marie"],"dc:date.accessioned":["2024-05-15T08:01:15Z"],"dc:date.available":["2024-05-15T08:01:15Z"],"dc:date.issued":["2024-05-14"],"dc:description.abstract":["Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing perfusion-based imaging protocols. Using this method, we examined transport associated with invasion in a murine GL261 cell line. We found that elevated interstitial fluid velocity magnitudes, decreased diffusion coefficients and regions with accumulating flow were significantly associated with invasion. We tested the validity of our invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions indicating location-specific structures may drive both interstitial flow and corresponding invasion heterogeneities. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Over-expression of VEGF-C in the tumor microenvironment neither enhanced drainage nor altered invasion in comparison to our control, indicating other tumor-secreted growth factors, such as VEGF-A, may play a larger role in mediating flow and invasion. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease."],"dc:description.abstractgeneral":["Glioblastoma is the most common and deadly primary brain tumor with an average survival of 15 months following diagnosis. Characterized as highly infiltrative with diffuse tumor margins, complete resection and annihilation of tumor cells is impossible following current standard of care therapies. Thus, tumor recurrence is inevitable. Interstitial fluid surrounds all of the cells in the body and has been linked to elevated invasion in glioma, which highlights the importance of this understudied fluid compartment in the brain. The primary objective of this dissertation was to identify specific interstitial fluid transport behaviors associated with elevated invasion surrounding glioma tumors. We first describe our methods to measure interstitial fluid flow in the brain using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), a clinically used, non-invasive imaging modality. We highlight the versatility of the technique and the possibilities that could arise from widespread adoption into existing imaging projects. Using this method, we examined transport associated with cancer cell invasion in a mouse tumor cell line. We found that interstitial fluid speeds were elevated while diffusion was decreased in regions of invasion. Further, regions that had interstitial fluid flow congregation were significantly associated with invasion. We tested the validity of these invasive trends by extending our analysis to multiple, clinically-relevant tumor locations in the brain. Interestingly, we found invasion did not follow the same trends across brain regions, indicating location-specific structures may drive both interstitial flow and invasion differences. Lastly, we aimed to manipulate flow by engaging with the meningeal lymphatics, an established pathway for interstitial fluid drainage. Following administration of a meningeal lymphatic-relevant protein, we saw no changes in flow or invasion in comparison to our untreated control, indicating other tumor-secreted proteins may play a larger role in these responses. Taken together, by identifying specific transport factors associated with invasion, we may be better equipped to target and treat infiltrative tumor margins, ultimately extending survival in patients diagnosed with this devastating disease."],"dc:description.degree":["Doctor of Philosophy"],"dc:format.medium":["ETD"],"dc:identifier.other":["vt_gsexam:39791"],"dc:identifier.uri":["https://hdl.handle.net/10919/118979"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["interstitial fluid flow","glioblastoma","DCE-MRI","invasion","transport","vasculature"],"dc:title":["Examining location-specific invasive patterns: linking interstitial fluid and vasculature in glioblastoma"],"dc:type":["Dissertation"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:19:15Z"}