title: Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy.
abstract: Definitive diagnosis of malignancy is often challenging due to limited availability of human cell or tissue samples and morphological similarity with certain benign conditions. Our recently developed novel technology-spatial-domain low-coherence quantitative phase microscopy (SL-QPM)-overcomes the technical difficulties and enables us to obtain quantitative information about cell nuclear architectural characteristics with nanoscale sensitivity. We explore its ability to improve the identification of malignancy, especially in cytopathologically non-cancerous-appearing cells. We perform proof-of-concept experiments with an animal model of colorectal carcinogenesis-APC(Min) mouse model and human cytology specimens of colorectal cancer. We show the ability of in situ nanoscale nuclear architectural characteristics in identifying cancerous cells, especially in those labeled as "indeterminate or normal" by expert cytopathologists. Our approach is based on the quantitative analysis of the cell nucleus on the original cytology slides without additional processing, which can be readily applied in a conventional clinical setting. Our simple and practical optical microscopy technique may lead to the development of novel methods for early detection of cancer.
authors.affiliation: University of Pittsburgh, Department of Medicine, Pittsburgh, PA 15232, USA.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.forename: Rajan K
authors.initials: RK
authors.lastname: Bista
authors.forename: Walid E
authors.initials: WE
authors.lastname: Khalbuss
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Shikhar
authors.initials: S
authors.lastname: Uttam
authors.forename: Kevin
authors.initials: K
authors.lastname: Staton
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Brentnall
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008858:Microscopy, Phase-Contrast / Q000295:instrumentation*; D036103:Nanotechnology / Q000295:instrumentation*; D041623:Tomography, Optical Coherence / Q000295:instrumentation*