{"doi":"10.1038/s41598-024-76908-7","title":"Handheld multiphoton and pinhole-free reflectance confocal microscopy enables noninvasive, real-time cross-sectional imaging in skin","abstract":"Biopsy-based histology has been the foundation of disease diagnosis and management for over a century. A long-sought goal in dermatology is the development of an imaging modality with sufficient resolution and compositional detail to noninvasively interrogate skin histology in vivo. Here, we describe a system that achieves this goal using cross-sectionally scanned, multimodal microscopy (cross-modal). Cross-modal combines multiphoton and reflectance confocal microscopy into one compact system with coordinated three-axis scanning that preserves optical resolution in cross-section. A custom pinhole-free mechanism employing finite-infinite conjugates further simplifies and stabilizes confocal alignment. Evaluated in participants ages 9-81 and Fitzpatrick skin types (FST) 1-5, cross-modal images revealed histological details analogous to those obtained from traditional biopsied tissue. We observed dermal elastosis in sun-damaged skin, elevated melanin in pigmented skin, basaloid nests in basal cell carcinoma, and elongated rete ridges in seborrheic keratosis, supporting cross-modal's potential to deliver histological insights noninvasively.","journal":"Scientific Reports","year":2024,"id":437390,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":737581,"name":"Roberto A. Novoa","orcid":"0000-0002-7955-0536","position":1,"is_corresponding":false},{"id":558961,"name":"Justin Ko","orcid":"0000-0003-4232-5906","position":2,"is_corresponding":false},{"id":1246845,"name":"Gabriel N. Sanchez","orcid":null,"position":3,"is_corresponding":false},{"id":1246844,"name":"Kate L. Montgomery","orcid":null,"position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39478114","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":[]}