Fast intraoperative detection of primary central nervous system lymphoma and differentiation from common central nervous system tumors using stimulated Raman histology and deep learning
David Reinecke, Nader Maarouf, Andrew Smith, Daniel Alexander Alber, John Markert, Nicolas K. Goff, Todd Hollon, Asadur Chowdury, Cheng Jiang, Xinhai Hou, Anna-Katharina Meißner, Gina Fürtjes, Maximilian I. Ruge, Daniel Rueß, Thomas Stehlé, Abdulkader Al-Shughri, L. Körner, Georg Widhalm, Thomas Roetzer-Pejrimovsky, John G. Golfinos, Matija Snuderl, Volker Neuschmelting, Daniel A. Orringer
Abstract
BACKGROUND: Accurate intraoperative diagnosis is crucial for differentiating between primary central nervous system (CNS) lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. METHODS: We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within <3 min. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and 2 additional independent test cohorts. We trained on 54 000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/nonneoplastic lesions. Training and test data were collected from 4 tertiary international medical centers. The final histopathological diagnosis served as ground truth. RESULTS: In the prospective test cohort of PCNSL and non-PCNSL entities (n = 160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ± 0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n = 420, n = 59) reached balanced accuracy rates of 95.44% ± 0.74 and 95.57% ± 2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features. CONCLUSIONS: RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within 3 min, enabling fast clinical decision-making and subsequent treatment strategy planning.