{"doi":"10.1101/2025.08.17.670744","title":"Inverse-scattering in biological samples via beam-propagation","abstract":"Multiple scattering limits optical imaging in thick biological samples by scrambling sample-specific information. Physics-based inverse-scattering methods aim to computationally recover this information, often using non-convex optimization to reconstruct the scatter-corrected sample. However, this non-convexity can lead to inaccurate reconstructions, especially in highly scattering samples. Here, we show that various implementation strategies for even the same inverse-scattering method significantly affect reconstruction quality. We demonstrate this using multi-slice beam propagation (MSBP), a relatively simple nonconvex inverse-scattering method that reconstructs a scattering sample's 3D refractive-index (RI). By systematically conducting MSBP-based inverse-scattering on both phantoms and biological samples, we showed that an amplitude-only cost function in the inverse-solver, combined with angular and defocus diversity in the scattering measurements, enabled high-quality, fully-volumetric RI imaging. This approach achieved subcellular resolution and label-free 3D contrast across diverse, multiple-scattering samples. These results lay the groundwork for robust use of inverse-scattering techniques to achieve biologically interpretable 3D imaging in increasingly thick, multicellular samples, introducing a new paradigm for deep-tissue computational imaging.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556686,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1250807,"name":"Blythe Bolton","orcid":null,"position":1,"is_corresponding":false},{"id":1071464,"name":"Khashayar Moshksayan","orcid":"0000-0002-5240-8193","position":2,"is_corresponding":false},{"id":1013056,"name":"Rishika Khanna","orcid":null,"position":3,"is_corresponding":false},{"id":1235030,"name":"Mary E. Swartz","orcid":"0000-0002-7601-0147","position":4,"is_corresponding":false},{"id":1456366,"name":"Michał Ziemczonok","orcid":"0000-0002-4802-1105","position":5,"is_corresponding":false},{"id":371425,"name":"Mohini Kamra","orcid":"0009-0004-2405-3120","position":6,"is_corresponding":false},{"id":302785,"name":"Karin Allenspach","orcid":"0000-0002-2168-5809","position":7,"is_corresponding":false},{"id":140050,"name":"Sapun H. Parekh","orcid":"0000-0001-8522-1854","position":8,"is_corresponding":false},{"id":1456367,"name":"Małgorzata Kujawińska","orcid":"0000-0001-6521-6951","position":9,"is_corresponding":false},{"id":348306,"name":"Johann K. Eberhart","orcid":"0000-0001-5258-2477","position":10,"is_corresponding":false},{"id":554327,"name":"Elif Sarinay Cenik","orcid":"0000-0001-8514-5505","position":11,"is_corresponding":false},{"id":382820,"name":"Adela Ben‐Yakar","orcid":"0000-0003-3468-6146","position":12,"is_corresponding":false},{"id":1235031,"name":"Shwetadwip Chowdhury","orcid":"0000-0002-6142-0231","position":13,"is_corresponding":false},{"id":1235029,"name":"Jeongsoo Kim","orcid":"0000-0003-0965-0424","position":0,"is_corresponding":true}],"reference_count":123,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:13.130091Z","pmid":"40894552","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}