{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:19:15Z","timestamp":1784006355022,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["358944"],"award-info":[{"award-number":["358944"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We have established a comprehensive sample handling protocol designed for the multiscale assessment of epileptogenic tissue. This protocol aims to identify novel therapeutic targets and enhance the diagnosis and stratification of patients with drug\u2010resistant epilepsy, thereby optimizing their treatment with anti\u2010seizure medications and surgical interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with drug\u2010resistant focal epilepsy, recommended for surgical treatment, are recruited after detailed multidisciplinary preoperative evaluation at the Epilepsy Center at Kuopio University Hospital in Finland. A day before the resective surgery, patients undergo magnetic resonance imaging (MRI) including advanced methodologies. During the surgery, each piece of resected tissue is placed under oxygenation on ice\u2010cold artificial cerebral spinal fluid solution. The pieces are then immediately transported to the laboratory, assessed by a neuropathologist, and sliced for both clinical diagnosis and research. Two adjacent slices are provided for research and are sent to the University of Eastern Finland.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The developed sample handling protocol provides the opportunity for detailed characterization of the tissue from the same patient using emerging imaging, electrophysiology, and molecular biology technologies. We have optimized the conditions for preserving the resected tissue alive for electrophysiological measurements and simultaneously making possible ex\u00a0vivo studies including multi\u2010omics acquisition, electron microscopy, histology, and MRI. Our protocol enables the mapping of functional readouts to structural and molecular alterations in human tissue. Our goal is to integrate multimodal data and co\u2010register the resected tissues within the whole brain's in\u00a0vivo MRI space. This approach aims to enhance the characterization and localization of epileptogenic zones and refine surgical treatment targets by identifying abnormalities in global connectivity and structural patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>We have successfully developed a systematic protocol for the collection and analysis of multimodal data. This protocol aims to elucidate the structural, functional, and molecular characteristics that render tissue epileptogenic, thereby enhancing the diagnosis and subsequent care of patients with epilepsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>We developed a new protocol for collecting and studying brain tissue removed during epilepsy surgery. By keeping the tissue alive and analyzing it with multiple techniques\u2014such as imaging, electrophysiology, and molecular biology\u2014we can better understand how epilepsy develops. This approach will help doctors identify treatment targets more precisely and improve diagnosis and care for people with drug\u2010resistant epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70174","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:31:03Z","timestamp":1764934263000},"page":"347-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multimodal approach to characterize surgically removed epileptogenic zone from patients with focal drug\u2010resistant epilepsy: From operating room to wet lab"],"prefix":"10.1002","volume":"11","author":[{"given":"Jenni","family":"Kyyri\u00e4inen","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Della Pietra","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6172-7842","authenticated-orcid":false,"given":"Mastaneh","family":"Torkamani\u2010Azar","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"G\u00f3mez\u2010Budia","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Abushik","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliia","family":"Novosolova","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Eronen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Narvaez","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Paasonen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"},{"name":"NeuroCenter Neurosurgery Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Lezhneva","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-5686","authenticated-orcid":false,"given":"Anssi","family":"Pelkonen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmila","family":"Saveleva","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Huotarinen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"},{"name":"NeuroCenter Neurosurgery Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Belevich","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Institute of Biotechnology, Helsinki Institute of Life Science University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eija","family":"Jokitalo","sequence":"additional","affiliation":[{"name":"Electron Microscopy Unit, Institute of Biotechnology, Helsinki Institute of Life Science University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Kuopio Epilepsy Center Epilepsy Surgery Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Jutila","sequence":"additional","affiliation":[{"name":"Kuopio Epilepsy Center Kuopio University Hospital, Member of ERN EpiCARE  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomas","family":"Rauramaa","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"},{"name":"Department of Pathology Kuopio University Hospital, University of Kuopio  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arto","family":"Immonen","sequence":"additional","affiliation":[{"name":"NeuroCenter Neurosurgery Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville","family":"Leinonen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"},{"name":"NeuroCenter Neurosurgery Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-5860","authenticated-orcid":false,"given":"Jussi","family":"Tohka","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Gr\u00f6hn","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-5131","authenticated-orcid":false,"given":"Reetta","family":"K\u00e4lvi\u00e4inen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"},{"name":"Kuopio Epilepsy Center Kuopio University Hospital, Member of ERN EpiCARE  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Malm","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-2056","authenticated-orcid":false,"given":"Alejandra","family":"Sierra","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1703784"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.17237"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535\u20107597.18.1.12"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.18175"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0B013E3283515DB9"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.13699"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YEBEH.2024.110056"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208007"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NICL.2021.102602"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13313"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701\u2010023\u201005611\u20109"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010024\u201001782\u20105"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111873"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14934"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.XPRO.2024.103313"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNANA.2011.00008"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAC224"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/EPI4.13093"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.15612"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.01.065"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa076"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphy.2021.793966"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0213252\/3309344"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25590"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00433"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2015.00059"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP275413"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2013.00134"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12021\u2010019\u201009431\u20100"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS11010124\/S1"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460\u20109568.2000.00156.x"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1460\u20109568.2012.08255.X"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf6484"},{"key":"e_1_2_12_35_1","doi-asserted-by":"crossref","unstructured":"DougalisA AbushikP PelkonenA GiudiceL G\u00f3mez\u2010BudiaM NovosolovaN et\u00a0al.Early amyloid spine response and impaired synaptic transmission of pyramidal neurons in human biopsies with Alzheimer's disease\u2010related pathology.bioRxiv.2025.https:\/\/doi.org\/10.1101\/2025.01.07.630516","DOI":"10.1101\/2025.01.07.630516"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/CERCOR\/BHV188"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2023.110055"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018752\u20107"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010022\u201001453\u20101"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010022\u201001095\u20105"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.005"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13502"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2009.02334.x"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586\u2010022\u201000131\u20109"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117529"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PBIO.1002340"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201001699\u2010w"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2016.18"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2016.44"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70174","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi4.70174","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70174","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:41:39Z","timestamp":1770993699000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/epi4.70174"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70174","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]},"assertion":[{"value":"2025-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}