Super-resolution of biomedical volumes with 2D supervision

Volumetric biomedical microscopy has the potential to increase the diagnostic information extracted from clinical tissue specimens and improve the diagnostic accuracy of both human pathologists and computational pathology models. Unfortunately, barriers to integrating 3-dimensional (3D) volumetric microscopy into clinical medicine include long imaging times, poor depth / z-axis resolution, and an insufficient amount of high-quality volumetric data. Leveraging the abundance of high-resolution 2D microscopy data, we introduce masked slice diffusion for super-resolution (MSDSR), which exploits the inherent equivalence in the data-generating distribution across all spatial dimensions of biological specimens. This intrinsic characteristic allows for super-resolution models trained on high-resolution images from one plane (e.g., XY) to effectively generalize to others (XZ, YZ), overcoming the traditional dependency on orientation. We focus on the application of MSDSR to stimulated Raman histology (SRH), an optical imaging modality for biological specimen analysis and intraoperative diagnosis, characterized by its rapid acquisition of high-resolution 2D images but slow and costly optical z-sectioning. To evaluate MSDSR's efficacy, we introduce a new performance metric, SliceFID, and demonstrate MSDSR's superior performance over baseline models through extensive evaluations. Our findings reveal that MSDSR not only significantly enhances the quality and resolution of 3D volumetric data, but also addresses major obstacles hindering the broader application of 3D volumetric microscopy in clinical diagnostics and biomedical research.

Contrastive Representation Learning for Rapid Intraoperative Diagnosis of Skull Base Tumors Imaged Using Stimulated Raman Histology

Background: Accurate diagnosis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative diagnosis can be challenging due to tumor diversity and lack of intraoperative pathology resources. Objective: To develop an independent and parallel intraoperative pathology workflow that can provide rapid and accurate skull base tumor diagnoses using label-free optical imaging and artificial intelligence (AI). Method: We used a fiber laser-based, label-free, non-consumptive, high-resolution microscopy method ($<$ 60 sec per 1 $\times$ 1 mm$^\text{2}$), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of skull base tumor patients. SRH images were then used to train a convolutional neural network (CNN) model using three representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained CNN models were tested on a held-out, multicenter SRH dataset. Results: SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the three representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to identify tumor-normal margins and detect regions of microscopic tumor infiltration in whole-slide SRH images. Conclusion: SRH with AI models trained using contrastive representation learning can provide rapid and accurate intraoperative diagnosis of skull base tumors.