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One example case is found in tuberous sclerosis complex (TSC), a developmental disorder characterized by systemic growth of benign tumors. Within resected brain tissues from patients with TSC, detection of abnormally enlarged balloon cells (BCs) is pathognomonic for this disorder. Though BCs can be identified by an expert neuropathologist, little is known about the specificity and broad applicability of protein markers for these cells, complicating classification of proposed BCs identified in experimental models of this disorder. Here, we report the development of a customized machine learning pipeline (BAlloon IDENtifier; BAIDEN) that was trained to prospectively identify BCs in tissue sections using a histological stain compatible with high\u2010dimensional cytometry. This approach was coupled to a custom 36\u2010antibody panel and imaging mass cytometry (IMC) to explore the expression of multiple previously proposed BC marker proteins and develop a descriptor of BC features conserved across multiple tissue samples from patients with TSC. Here, we present a modular workflow encompassing BAIDEN, a custom antibody panel, a control sample microarray, and analysis pipelines\u2014both open\u2010source and in\u2010house\u2014and apply this workflow to understand the abundance, structure, and signaling activity of BCs as an example case of how high\u2010dimensional imaging can be applied within human tissues.<\/jats:p>","DOI":"10.1002\/cyto.b.22194","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T04:59:27Z","timestamp":1719896367000},"page":"35-54","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multiparameter quantitative analyses of diagnostic cells in brain tissues from tuberous sclerosis complex"],"prefix":"10.1002","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-5641","authenticated-orcid":false,"given":"Jerome S.","family":"Arceneaux","sequence":"first","affiliation":[{"name":"Department of 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University Children's Hospital and Health Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Weatherspoon","sequence":"additional","affiliation":[{"name":"Neuroscience Institute Le Bonheur Children's Hospital  Memphis Tennessee USA"},{"name":"Department of Pediatrics University of Tennessee Health Science Center  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8138-5330","authenticated-orcid":false,"given":"Bret C.","family":"Mobley","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, &amp; Immunology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3730-7351","authenticated-orcid":false,"given":"Kevin C.","family":"Ess","sequence":"additional","affiliation":[{"name":"Department of Cell &amp; Developmental 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