Minimally Invasive, Label-Free, Point-of-Care Histopathological Diagnostic Platform of Malignant Tumors of the Female Reproductive System Based on Raman Spectroscopy and Machine Learning.

Journal: The journal of physical chemistry letters
Published Date:

Abstract

Fast intraoperative histopathology is critical for optimal surgery in ovarian, endometrial and cervical cancers, yet frozen-section pathology is slow and resource-intensive. We obtained 4750 Raman spectra from 85 human gynecological tissue specimens spanning 19 histopathological classes. Spectra were preprocessed and classified with five machine-learning algorithms; performance was assessed by stratified train-test splits (70%:30%). Support-vector machines achieved 100% accuracy (AUC = 1.00) across all classes, outperforming random forest (96-99%) and k-nearest-neighbor (97-99%). Single-spectra acquisition required 30 s and automated prediction <8 s, enabling real-time decisions within 1 min. Raman-derived biochemical fingerprints highlighted subtype-specific alterations in nucleic acids, amino acids and collagen that are invisible to routine microscopy. Coupling Raman spectroscopy with machine learning yields an ultrarapid, label-free platform that accurately discriminates malignant, benign and premalignant lesions of the female reproductive tract at the point of care. The technology could reduce operative time, minimize repeat surgery and extend high-quality histopathology to low-resource settings.

Authors

  • Liangliang Jiang
    Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150086, China.
  • Siqi Gong
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang, 150081, PR China.
  • Zibo Gao
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang, 150081, PR China.
  • Xinyu Yao
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Harbin City, Heilongjiang Province 150081, China.
  • Chaochao Ma
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
  • Yaowen Xing
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang 150081, PR China.
  • Liping Zhou
    DigiM Solution LLC, Burlington, MA 01803, USA.
  • Jin Sun
    Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
  • Jing Wu
    School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, Jiangsu, China.
  • Yingji Wang
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang, 150081, PR China.
  • Jing Wang
    Endoscopy Center, Peking University Cancer Hospital and Institute, Beijing, China.
  • Jian-An Huang
    Research Unit of Health Sciences and Technology (HST), Faculty of Medicine University of Oulu, Oulu, 999018, Finland.
  • Yanli Wu
    State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang 150081, PR China.
  • Sijia Liu
    These authors contributed equally to this study and Dr. Li is now working at IBM; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Computer Science and Engineering, University at Buffalo, Buffalo, NY, USA.
  • Yang Li
    Occupation of Chinese Center for Disease Control and Prevention, Beijing, China.