ArticleProceedings of the National Academy of Sciences of the United States of America2014
Assessment of breast pathologies using nonlinear microscopy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 213 citations in OpenAlex.
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- Development and validation of a collagen score-based prediction model for neoadjuvant chemoimmunotherapy efficacy in locally advanced esophageal squamous cell carcinoma.Journal of thoracic disease · 2026Article
- Deep UV laser scanning microscopy with integrated 1050 nm spectral-domain optical coherence tomography for multi-contrast tissue imaging.Biomedical optics express · 2025Article
- Vacuum-based specimen holder for rapid surgical specimen imaging.Biomedical optics express · 2025Article
- Real-time histological evaluation of gastrointestinal tissue using non-linear microscopy.Journal of clinical pathology · 2025Article
- Fast and label-free 3D virtual H&E histology via active phase modulation-assisted dynamic full-field OCT.Npj imaging · 2025Article
- Modeling intratumor heterogeneity in breast cancer.Biofabrication · 2024Review
- Rapid Examination of Nonprocessed Renal Cell Carcinoma Using Nonlinear Microscopy.Archives of pathology & laboratory medicine · 2024Article
- Metabolic light absorption, scattering, and emission (MetaLASE) microscopy.Science advances · 2024Article
- Rapid examination of lung tissues by nonlinear microscopy.American journal of clinical pathology · 2024Article
- Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.Journal of biomedical optics · 2024Article
- Macroscopic inelastic scattering imaging using a hyperspectral line-scanning system identifies invasive breast cancer in lumpectomy and mastectomy specimens.Journal of biomedical optics · 2024Article
- Piston-based specimen holder for rapid surgical and biopsy specimen imaging.Biomedical optics express · 2024Article
- Virtual Staining of Nonfixed Tissue Histology.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Review
- Current Landscape of Advanced Imaging Tools for Pathology Diagnostics.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Review
- An end-to-end workflow for nondestructive 3D pathology.Nature protocols · 2024Review
- Article
- A Pilot Validation Study Comparing Fluorescence-Imitating Brightfield Imaging, A Slide-Free Imaging Method, With Standard Formalin-Fixed, Paraffin-Embedded Hematoxylin-Eosin-Stained Tissue Section Histology for Primary Surgical Pathology Diagnosis.Archives of pathology & laboratory medicine · 2024Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Rapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen. Imaging was performed on fresh, intact specimens without the need for fixation, embedding, and sectioning required for conventional histopathology. A visualization method to aid pathological interpretation is presented that maps NLM contrast from two-photon fluorescence and second harmonic signals to features closely resembling histopathology using hematoxylin and eosin staining. Mosaicking is used to overcome trade-offs between resolution and field of view, enabling imaging of subcellular features over square-centimeter specimens. After NLM examination, specimens were processed for standard paraffin-embedded histology using a protocol that coregistered histological sections to NLM images for paired assessment. Blinded NLM reading by three pathologists achieved 95.4% sensitivity and 93.3% specificity, compared with paraffin-embedded histology, for identifying invasive cancer and ductal carcinoma in situ versus benign breast tissue. Interobserver agreement was κ = 0.88 for NLM and κ = 0.89 for histology. These results show that NLM achieves high diagnostic accuracy, can be rapidly performed on unfixed specimens, and is a promising method for intraoperative margin assessment.
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