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Yet its limited optical penetration has prevented scattering-based methods from being applied to whole-organ pathology mapping. Here we present clearing-assisted scattering tomography (CAST), a high-throughput, label-free whole-brain mesoscope enabled by selective lipid clearance for scattering enhancement (SELiC). SELiC modulates endogenous refractive-index heterogeneity in cleared tissue, providing whole-brain optical penetration while retaining strong scattering contrast from amyloid plaques and white-matter fibre bundles. CAST enables volumetric imaging of intact mouse brains and brain-wide mapping of amyloid plaque pathology across anatomical regions. This platform establishes a scalable route for label-free, system-level analysis of amyloid pathology and tissue architecture in Alzheimer\u2019s disease (AD) models.<\/jats:p>","DOI":"10.64898\/2026.06.28.735093","type":"posted-content","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T22:20:13Z","timestamp":1782771613000},"source":"Crossref","is-referenced-by-count":0,"title":["High-throughput whole-brain scattering imaging resolves amyloid plaques through clearing-assisted contrast modulation"],"prefix":"10.64898","author":[{"given":"Chong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology, Massachusetts General Hospital, Boston, MA 02129, USA"},{"name":"Center for Inflammation Imaging, Mass General Brigham, Somerville, MA 02145, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Massachusetts General Hospital, Boston, MA 02129, USA"},{"name":"Center for Inflammation Imaging, Mass General Brigham, Somerville, MA 02145, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-7473","authenticated-orcid":false,"given":"Jian","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiology, Massachusetts General Hospital, Boston, MA 02129, USA"},{"name":"Center for Inflammation Imaging, Mass General Brigham, Somerville, MA 02145, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070116551623000_2026.06.28.735093v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.067"},{"key":"2026070116551623000_2026.06.28.735093v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00712-8"},{"key":"2026070116551623000_2026.06.28.735093v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01468-5"},{"key":"2026070116551623000_2026.06.28.735093v1.4","doi-asserted-by":"crossref","unstructured":"Glaser, A. et al. 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