Rapid and Precise Diagnosis of Retroperitoneal Liposarcoma with Deep-Learned Label-Free Molecular Microscopy.

The retroperitoneal liposarcoma (RLPS) is a rare malignancy whose only curative therapy is surgical resection. However, well-differentiated liposarcomas (WDLPSs), one of its most common types, can hardly be distinguished from normal fat during operation without an effective margin assessment method, jeopardizing the prognosis severely with a high recurrence risk. Here, we combined dual label-free nonlinear optical modalities, stimulated Raman scattering (SRS) microscopy and second harmonic generation (SHG) microscopy, to image two predominant tissue biomolecules, lipids and collagen fibers, in 35 RLPSs and 34 normal fat samples collected from 35 patients. The produced dual-modal tissue images were used for RLPS diagnosis based on deep learning. Dramatically decreasing lipids and increasing collagen fibers during tumor progression were reflected. A ResNeXt101-based model achieved 94.7% overall accuracy and 0.987 mean area under the ROC curve (AUC) in differentiating among normal fat, WDLPSs, and dedifferentiated liposarcomas (DDLPSs). In particular, WDLPSs were detected with 94.1% precision and 84.6% sensitivity superior to existing methods. The ablation experiment showed that such performance was attributed to both SRS and SHG microscopies, which increased the sensitivity of recognizing WDLPS by 16.0 and 3.6%, respectively. Furthermore, we utilized this model on RLPS margins to identify the tumor infiltration. Our method holds great potential for accurate intraoperative liposarcoma detection.