Brain Pathology最新文献

{"title":"3D imaging of neuronal inclusions and protein aggregates in human neurodegeneration by multiscale x-ray phase-contrast tomography.","authors":"Jonas Franz, Jakob Reichmann, Marina Eckermann, Thea Würfel, Artur Groh, Syed Fatima Qadri, Katja Schulz, Brit Mollenhauer, Christine Stadelmann, Tim Salditt","doi":"10.1111/bpa.70044","DOIUrl":"https://doi.org/10.1111/bpa.70044","url":null,"abstract":"<p><p>This study leverages x-ray phase-contrast tomography (XPCT) for detailed analysis of neurodegenerative diseases, focusing on the three-dimensional (3D) visualization and quantification of neuropathological features within fixed human postmortem tissue. XPCT with synchrotron radiation offers micrometer and even sub-micron resolution, enabling us to examine intra- and extraneuronal aggregates and inclusions such as Lewy bodies (LBs), granulovacuolar degeneration (GvD), Hirano bodies (HBs), neurofibrillary tangles (NFTs), β-amyloid plaques, and vascular amyloid deposits in three dimensions. In the reconstructions, we identified the highest electron densities in Hirano and LBs, while NFTs exhibited no significant increase in XPCT contrast. Using cutting-edge high-resolution x-ray synchrotron beamlines, we were now able to detect even detect subcellular differences in electron densities found in GvD. Small-scale inhomogeneities of the electron density were also detected in LBs, potentially relating to inclusions of organelles. Additionally, we reveal here a peculiar 3D geometry of HBs and demonstrate the co-occurrence with GvD in the same neuron. These findings underscore the potential of XPCT as a powerful, label-free tool for spatially resolved neuropathological investigations, opening new avenues for the systematic 3D characterization of inclusions and aggregates in neurodegeneration.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70044"},"PeriodicalIF":6.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a distinct epigenetic subgroup with inferior PFS in intracranial mesenchymal tumors with FET::CREB fusion.","authors":"Yong Lin, Yun Ning, Yang Lan, Yu-Juan Cao, Rui-Jiao Zhao, Hai-Nan Li, Song Duan, Wei-Wei Fu, Hai-Bo Wu, Feng Wu, Xiu-Wu Bian, Tao Luo, Xiao-Hong Yao","doi":"10.1111/bpa.70040","DOIUrl":"https://doi.org/10.1111/bpa.70040","url":null,"abstract":"<p><p>Intracranial mesenchymal tumors (IMTs) with FET::CREB fusion are newly recognized molecular entities, provisionally classified into subgroups A and B. Although Group B has been partially characterized, the clinicopathological and molecular heterogeneity of Group A remains poorly defined. This study aimed to conduct an integrated analysis of 6 newly diagnosed and 20 previously reported IMTs with FET::CREB fusion. Notably, Group A was further stratified into two distinct entities A1 and A2 based on unsupervised methylation profiling. Compared to Group A1, Group A2 demonstrated significantly shorter progression-free survival (PFS), a higher proportion of male patients, and less frequent occurrence of myxoid-rich stroma. Amplification of 10p15.3 was frequently observed in Group A2. Furthermore, GLUT-1 could serve as a potential diagnostic indicator in IMTs with FET::CREB fusion. Overall, we identified a new subgroup of IMTs with FET::CREB fusion with poor PFS and distinct clinicopathological and molecular features, offering actionable insights to refine therapeutic strategies and improve risk stratification in this emerging diagnostic category.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70040"},"PeriodicalIF":6.2,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysmorphic neurons express markers of inhibitory glycinergic signaling in focal cortical dysplasia IIb.","authors":"Ameesha Paliwal, Kevin Faust, Okty Abbasi Borhani, Mugeng Liu, Lauren Omoto, Evelyn Rose Kamski-Hennekam, Parsa Babaei Zadeh, Rifat Shahriar Sajid, Phedias Diamandis","doi":"10.1111/bpa.70043","DOIUrl":"https://doi.org/10.1111/bpa.70043","url":null,"abstract":"<p><p>Focal cortical dysplasia (FCD) is a neurodevelopmental malformation that often manifests as medically refractory epilepsy. A key histological hallmark of FCD type II is the presence of cytomegalic dysmorphic neurons (CDNs), which are considered to be major contributors to cortical network hyperexcitability. However, the relatively low frequency of CDNs within resected lesions has challenged their unbiased molecular characterization. Here, we leverage deep learning approaches to objectively map key anatomical compartments of FCD IIb and guide regional spatial transcriptomic profiling. Using this approach, we generate an anatomical transcriptional catalog of type IIb FCD, and uncover non-canonical markers of signaling and neurotransmitter pathways in CDNs that may serve as new therapeutic targets for this debilitating disorder.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70043"},"PeriodicalIF":6.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialylation patterns in cerebral amyloid angiopathy.","authors":"Caitlyn Fastenau, Rebecca Crisp, Mallory Keating, Elizabeth Ochoa, Timothy E Richardson, Margaret E Flanagan, Jamie M Walker, Sarah C Hopp, Kevin F Bieniek","doi":"10.1111/bpa.70042","DOIUrl":"https://doi.org/10.1111/bpa.70042","url":null,"abstract":"<p><p>Glycosylation is the most common form of post-translational modification in the brain and becomes significantly altered in the context of neurodegeneration. One notable alteration is an enrichment of terminal sialic acid (SA) modifications. Previous studies provide evidence of increased sialylation on microglia, the innate immune cell of the brain, in Alzheimer's disease (AD), particularly near amyloid beta plaques. Yet, there is little understanding of the relationship between SA and other amyloid beta-related diseases like Cerebral Amyloid Angiopathy (CAA). Nearly half of all AD cases have CAA; thus, it is critical to understand the relationship between amyloid pathology and SA modifications. The present study aimed to overcome this gap in knowledge by investigating sialylation patterns in AD cases with CAA compared with CAA-negative AD cases and amyloid-negative control cases. The localization of SA modifications was investigated in the frontal cortex of 30 post-mortem cases with or without diagnoses of AD and/or CAA. Quantitative digital pathology analyses were used to determine regional SA differences in parenchymal and leptomeningeal blood vessels. First, we found no difference in intravascular amyloid-beta levels between the parenchymal and leptomeningeal vessels of AD with CAA cases, suggesting no regional differences in this amyloid aggregation. Next, there was a visual increase in microglia sialylation surrounding parenchymal blood vessels in the CAA cases. Notably, there were significant differences in intravascular SA levels across the three comparison groups. AD cases with CAA had significantly greater sialylation levels in both the parenchymal and leptomeningeal vessels compared with the AD-only and control groups. This is a novel finding that supports the consideration of glycosylation changes that contribute to worse pathological outcomes in AD with CAA.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70042"},"PeriodicalIF":6.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOCIETY NEWS","authors":"Audrey Rousseau","doi":"10.1111/bpa.70041","DOIUrl":"10.1111/bpa.70041","url":null,"abstract":"&lt;p&gt;&lt;b&gt;The ISN is looking for a group of young motivated neuropathologists&lt;/b&gt; to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (&lt;span&gt;[email protected]&lt;/span&gt;) or Monika Hofer (&lt;span&gt;[email protected]&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;&lt;b&gt;The International Congress of Neuropathology (ICN)&lt;/b&gt; will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith and the ICN27 will be hosted by the British Neuropathological Society (BNS).&lt;/p&gt;&lt;p&gt;“On behalf of the British Neuropathological Society I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible centre, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.&lt;/p&gt;&lt;p&gt;Colin Smith&lt;/p&gt;&lt;p&gt;Congress President ISN 2027”&lt;/p&gt;&lt;p&gt;Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).&lt;/p&gt;&lt;p&gt;The &lt;b&gt;7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies&lt;/b&gt; will be held in conjunction with the 30th Annual Meeting &amp; Education Day of the Society for Neuro-Oncology &lt;b&gt;November 19-23, 2025&lt;/b&gt; in Honolulu, Hawaii.&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Brain Pathology has joined Wiley's Open Access&lt;/i&gt;&lt;/b&gt; portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount off the Open Access APC. For more information on the fees, please click here.&lt;/p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich&lt;/i&gt;&lt;/b&gt;. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested colleagues are invited to use this resource, which will be particularly useful for teaching and training (see link below). Colleagues are invited to contribute suitable cases of uncommon neurodegenerative diseases, if they wish to. The site allows photos to be taken via ‘screen save’ for certain characteristic pathologies (at ×20) without copyright restrictions, which may be very helpful.&lt;/p&gt;&lt;p&gt;Link: https://znp.smartzoom.com/S6&lt;/p&gt;&lt;p&gt;For information on how to co","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 6","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofilament light chain as a marker of peripheral nerve damage in vasculitic neuropathy? A cross-compartmental correlation analysis in patients undergoing nerve biopsy.","authors":"Simon Streit, Jenny Meinhardt, Niclas Gimber, John Kestenbach, Christin Siewert, Jan Schmoranzer, Christian Meisel, Klemens Ruprecht, Frank L Heppner, Péter Körtvélyessy, Werner Stenzel","doi":"10.1111/bpa.70038","DOIUrl":"https://doi.org/10.1111/bpa.70038","url":null,"abstract":"<p><p>Vasculitic neuropathy remains challenging to diagnose and monitor because of its heterogeneous clinical and laboratory presentation. Blood-based biomarkers indicating nerve damage could serve as an additional diagnostic tool to ensure early diagnosis, precise therapeutic monitoring, and a more targeted anti-inflammatory treatment. A potential marker for this purpose is neurofilament light chain (NfL), a marker of neuroaxonal damage that is used as a biomarker in several diseases of the central and peripheral nervous system. NfL has also been suggested to reflect disease activity in patients with vasculitic neuropathy. However, its biodynamics and link to degeneration of peripheral nerve tissue remain unconfirmed. To investigate the usefulness of NfL as a marker of peripheral nerve damage in this context, we retrospectively assembled a cohort of 35 patients undergoing sural nerve biopsies (including patients with vasculitic neuropathy and other neuropathies). We then measured NfL in serum samples cryoarchived at the time of biopsy and correlated NfL levels with histological parameters. For our histological analysis, we quantified parameters of acute axonal degeneration and chronic axonal loss using a combination of manual, threshold-based, and supervised learning-based analyses. We found a significant positive correlation between parameters of acute axonal degeneration and serum-NfL levels that persisted after adjusting for age and concomitant central nervous system disease. We did not find a similar correlation with parameters of chronic axonal loss quantified in nerve biopsies. These findings support the value of NfL as a marker for acute axonal degeneration in patients with vasculitic neuropathy.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70038"},"PeriodicalIF":6.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A unified 3D reconstruction of microscopy and MRI in a brain showing Alzheimer's disease-related neuropathology.","authors":"Anneke Alkemade, Pierre-Louis Bazin, Evgeniya Kirilina, Kerrin Pine, Andreas Herrler, Ronald L A W Bleijs, J Max Kros, Lysanne Groenewegen, Sanne M M Vermorgen, Laura E Jonkman, Dick F Swaab, Rawien Balesar, Nikolaus Weiskopf, Birte U Forstmann","doi":"10.1111/bpa.70039","DOIUrl":"https://doi.org/10.1111/bpa.70039","url":null,"abstract":"<p><p>To bridge between detailed post-mortem neuropathological assessments and Magnetic Resonance Imaging (MRI), we have created and share a three-dimensional (3D) account of an entire human brain with an intermediate Alzheimer's disease neuropathologic change. We combined multimodal imaging, using cryosectioning, histology, immunocytochemistry, and quantitative ultra-high field 7 Tesla (T) magnetic resonance imaging (MRI) at submillimeter resolution. Amyloid-β and phosphorylated-tau immunoreactivity, cell soma, and nerve fibers were visualized, together with quantitative MR parameters. All data were coaligned with at 200 μm resolution and are openly shared. The use of whole-brain sections allows for a detailed assessment of neuropathological alterations, revealing clear differences between the left and right hemispheres in terms of pathological load of amyloid-β and phosphorylated-tau in a single brain showing Alzheimer's disease neuropathologic change. This resource opens the door for a combination of detailed correlations between neuroimaging and neuropathological microscopy observations, as well as for detailed MRI validation.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70039"},"PeriodicalIF":6.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cIMPACT-NOW update 11: Proposal on adaptation of diagnostic criteria for IDH- and H3-wildtype diffuse high-grade gliomas and for posterior fossa ependymal tumors.","authors":"Pieter Wesseling, David Capper, Guido Reifenberger, Chitra Sarkar, Cynthia Hawkins, Arie Perry, Bette Kleinschmidt-DeMasters, Takashi Komori, Werner Paulus, Vani Santosh, Martin van den Bent, Michael Weller, Stefan M Pfister, Uri Tabori, Dominique Figarella-Branger, Brent A Orr, David N Louis","doi":"10.1111/bpa.70035","DOIUrl":"https://doi.org/10.1111/bpa.70035","url":null,"abstract":"<p><p>The Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (cIMPACT-NOW) updates provide guidelines for the diagnosis of central nervous system (CNS) tumors and suggestions for future World Health Organization (WHO) classification. Following publication of the fifth edition WHO Classification of CNS Tumors (WHO CNS5) in 2021, the cIMPACT-NOW working group \"Clarification\" reviewed WHO CNS5 and prioritized two topics for further elucidation: (a) distinction of Glioblastoma, IDH-wildtype from Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype and (b) clarification of subgroups of posterior fossa (PF) ependymal tumors. Recommendations regarding the IDH- and H3-wildtype diffuse high-grade gliomas include: (1) use caution assigning CNS WHO grade 4 (diagnosis of Glioblastoma, IDH-wildtype) to a \"TERT promoter only\", histologically low-grade, IDH-wildtype tumor; (2) EGFR gene amplification and +7/-10 chromosome copy number alterations should not be used as solitary defining features for diagnosing high-grade gliomas as Glioblastoma, IDH-wildtype in patients <40 years of age; (3) Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype should be considered in the differential diagnosis in adults, especially those <40 years of age; (4) PDGFRA alteration, EGFR alteration, or MYCN amplification count as key molecular features of Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype only in patients <25 years. Guidelines for improved diagnosis of posterior fossa ependymal tumors include: (1) immunohistochemical demonstration of nuclear EZHIP supports classification as PF group A ependymoma; (2) a PF ependymoma with retained nuclear H3 K27me3 expression and no nuclear EZHIP overexpression for which DNA methylation profiling is not performed should be considered as PF ependymoma, \"not otherwise specified\"; (3) for emerging tumors not included in WHO CNS5, \"not elsewhere classified\" (NEC) can be added to the diagnosis. Of note, these recommendations are not formal changes to the WHO definitions and diagnostic criteria but are intended to provide diagnostic guidance in advance of WHO CNS6.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70035"},"PeriodicalIF":6.2,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitro-oleic acid activation of endothelial PPARγ signaling pathway alleviates neurovascular injury and improves functional outcomes in ischemic stroke.","authors":"Tianqing Xiong, Na Qiu, Andrew Ni, Xiaotao Xu, Ping Sun, Shun Li, Ke-Jie Yin","doi":"10.1111/bpa.70037","DOIUrl":"https://doi.org/10.1111/bpa.70037","url":null,"abstract":"<p><p>Nitro-oleic acid (OA-NO₂) is an endogenous peroxisome proliferator-activated receptor-γ (PPARγ) ligand and can activate this receptor under both physiological and pathological conditions. In this study, we explore the role and molecular mechanisms of OA-NO₂ in maintaining blood-brain barrier (BBB) integrity and enhancing neurovascular function during ischemic stroke, with a particular emphasis on the activation of endothelial PPARγ signaling pathways. Endothelial cell-selective PPARγ conditional knockout (EC-PPARγ cKO) and wild-type (WT) mice underwent 1 h middle cerebral artery occlusion (MCAO) with 1-7 days of reperfusion. Mice were treated with oleic acid (OA) or OA-NO₂ (5 mg/kg) via tail vein 2 h after MCAO. Neurobehavioral deficits were assessed on days 3, 5, and 7 after MCAO. Neuroinflammation and BBB function were assessed on days 1 or 2 after MCAO by immunohistochemistry, RT-qPCR, or Western blot analysis. Compared to OA controls, intravenous administration of OA-NO₂ led to reduced BBB leakage in ischemic brains, as indicated by a significant decrease in the extravasation of BBB tracers. This reduction in BBB leakage was also almost abolished in the EC-PPARγ cKO mice. Furthermore, OA-NO₂ treatment reduced brain infarction in stroke mice, but this protective effect was completely reversed in the EC-PPARγ cKO mice. Interestingly, OA-NO₂ treatment promoted a shift towards an anti-inflammatory microglial phenotype (M2) in the peri-infarct regions of WT mice, but not in EC-PPARγ cKO mice. Mechanistically, OA-NO₂ increased levels of major endothelial tight junction proteins in WT mice but not in EC-PPARγ cKO mice following ischemic stroke. These findings suggest that OA-NO₂ activation of endothelial PPARγ signaling cascade attenuates neurovascular injury after ischemic stroke.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70037"},"PeriodicalIF":6.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of automated and manual approaches for microglial quantification and classification: A focus on the HALO digital pathology platform.","authors":"Laura M Carr, Bianca Guglietti, Ing Chee Wee, Ian F Musgrave, Sanam Mustafa, Frances Corrigan, Lyndsey E Collins-Praino","doi":"10.1111/bpa.70036","DOIUrl":"10.1111/bpa.70036","url":null,"abstract":"<p><p>Phenotypic changes in microglia have been linked to multiple neurological conditions, such as dementia, Parkinson's disease, stroke and traumatic brain injury. Consistent identification and classification of microglia is essential in understanding potential links with neurological diseases. Currently, there are several ways by which the microglial population and morphology are assessed, including manually or using open-source image analysis platforms, such as ImageJ. A microglial classification module for the HALO digital pathology platform has been developed for this purpose but has not yet been validated within the literature. The current study therefore conducted a comparison of the performance of this HALO module to manual microglial analysis and to automated analysis via ImageJ using both human and rat brain tissue. In 5 μm thick human tissue, total and activated microglia/mm² counted by HALO showed strong positive correlations with both manual and ImageJ counts. HALO did not differ from the other methods for total microglia counts; however, Halo did differ from both manual and ImageJ methods in the number of activated microglia detected within the substantia nigra. In 20 μm rat tissue, total counts derived from HALO showed moderate positive correlations with both manual and ImageJ counting; however, activated counts on Halo were not positively correlated with any method. To our knowledge, this is the first study to systematically compare the Halo module to other common methods of microglia analysis. When applied to 5 μm tissue, the Halo module is comparable to manual counting and to automated analysis on ImageJ. However, when analyzing thicker tissue, Halo struggles to perform in line with these other methods, particularly for counts of activated microglia, likely due to increased cell density and the morphological complexity of microglia. These results highlight the importance of carefully tailoring image analysis parameters on automated counting methods to suit the needs of the tissue.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":" ","pages":"e70036"},"PeriodicalIF":6.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}