{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:21Z","timestamp":1792806141943,"version":"4.5.0"},"reference-count":44,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Inflammation and angiogenesis may play a role in the growth of sporadic and neurofibromatosis type 2 (NF2)\u2013related vestibular schwannoma (VS). The similarities in microvascular and inflammatory microenvironment have not been investigated. The authors sought to compare the tumor microenvironment (TME) in sporadic and NF2-related VSs using a combined imaging and tissue analysis approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Diffusion MRI and high-temporal-resolution dynamic contrast-enhanced (DCE) MRI data sets were prospectively acquired in 20 NF2-related and 24 size-matched sporadic VSs. Diffusion metrics (mean diffusivity, fractional anisotropy) and DCE-MRI\u2013derived microvascular biomarkers (transfer constant [K\n                      <jats:sup>trans<\/jats:sup>\n                      ], fractional plasma volume, tissue extravascular-extracellular space [v\n                      <jats:sub>e<\/jats:sub>\n                      ], longitudinal relaxation rate, tumoral blood flow) were compared across both VS groups, and regression analysis was used to evaluate the effect of tumor size, pretreatment tumor growth rate, and tumor NF2 status (sporadic vs NF2-related) on each imaging parameter. Tissues from 17 imaged sporadic VSs and a separate cohort of 12 NF2-related VSs were examined with immunohistochemistry markers for vessels (CD31), vessel permeability (fibrinogen), and macrophage density (Iba1). The expression of vascular endothelial growth factor (VEGF) and VEGF receptor 1 was evaluated using immunohistochemistry, Western blotting, and double immunofluorescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Imaging data demonstrated that DCE-MRI\u2013derived microvascular characteristics were similar in sporadic and NF2-related VSs. K\n                      <jats:sup>trans<\/jats:sup>\n                      (p &lt; 0.001), v\n                      <jats:sub>e<\/jats:sub>\n                      (p \u2264 0.004), and tumoral free water content (p \u2264 0.003) increased with increasing tumor size and pretreatment tumor growth rate. Regression analysis demonstrated that with the exception of mean diffusivity (p &lt; 0.001), NF2 status had no statistically significant effect on any of the imaging parameters or the observed relationship between the imaging parameters and tumor size (p &gt; 0.05). Tissue analysis confirmed the imaging metrics among resected sporadic VSs and demonstrated that across all VSs studied, there was a close association between vascularity and Iba1\n                      <jats:sup>+<\/jats:sup>\n                      macrophage density (r = 0.55, p = 0.002). VEGF was expressed by Iba1\n                      <jats:sup>+<\/jats:sup>\n                      macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The authors present the first in vivo comparative study of microvascular and inflammatory characteristics in sporadic and NF2-related VSs. The imaging and tissue analysis results indicate that inflammation is a key contributor to TME and should be viewed as a therapeutic target in both VS groups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2020.3.jns193230","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T03:37:59Z","timestamp":1590723479000},"page":"1419-1429","source":"Crossref","is-referenced-by-count":44,"title":["The microenvironment in sporadic and neurofibromatosis type II\u2013related vestibular schwannoma: the same tumor or different? A comparative imaging and neuropathology study"],"prefix":"10.3171","volume":"134","author":[{"given":"Daniel","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"},{"name":"Division of Informatics, Imaging and Data Sciences, Wolfson Molecular Imaging Centre (WMIC), University of Manchester;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine A.","family":"Donofrio","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"},{"name":"Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-loh","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Sciences, Wolfson Molecular Imaging Centre (WMIC), University of Manchester;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Sciences, Wolfson Molecular Imaging Centre (WMIC), University of Manchester;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Djoukhadar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erjon","family":"Agushi","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Sciences, Wolfson Molecular Imaging Centre (WMIC), University of Manchester;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathal J.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon K.","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wadeson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Hammerbeck-Ward","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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