Length-scale study in deep learning prediction for non-small cell lung cancer brain metastasis

Deep learning assisted digital pathology has the potential to impact clinical practice in significant ways. In recent studies, deep neural network (DNN) enabled analysis outperforms human pathologists. Increasing sizes and complexity of the DNN architecture generally improves performance at the cost of DNN's explainability. For pathology, this lack of DNN explainability is particularly problematic as it hinders the broader clinical interpretation of the pathology features that may provide physiological disease insights. To better assess the features that DNN uses in developing predictive algorithms to interpret digital microscopic images, we sought to understand the role of resolution and tissue scale and here describe a novel method for studying the predictive feature length-scale that underpins a DNN's predictive power. We applied the method to study a DNN's predictive capability in the case example of brain metastasis prediction from early-stage non-small-cell lung cancer biopsy slides. The study highlights the DNN attention in the brain metastasis prediction targeting both cellular scale (resolution) and tissue scale features on H&E-stained histological whole slide images. At the cellular scale, we see that DNN's predictive power is progressively increased at higher resolution (i.e., lower resolvable feature length) and is largely lost when the resolvable feature length is longer than 5 microns. In addition, DNN uses more macro-scale features (maximal feature length) associated with tissue organization/architecture and is optimized when assessing visual fields larger than 41 microns. This study for the first time demonstrates the length-scale requirements necessary for optimal DNN learning on digital whole slide images.

Single-shot volumetric fluorescence imaging with neural fields

Single-shot volumetric fluorescence (SVF) imaging offers a significant advantage over traditional imaging methods that require scanning across multiple axial planes as it can capture biological processes with high temporal resolution across a large field of view. Existing SVF imaging methods often require large, complex point spread functions (PSFs) to meet the multiplexing requirements of compressed sensing, which limits the signal-to-noise ratio, resolution and/or field of view. In this paper, we introduce the QuadraPol PSF combined with neural fields, a novel approach for SVF imaging. This method utilizes a cost-effective custom polarizer at the back focal plane and a polarization camera to detect fluorescence, effectively encoding the 3D scene within a compact PSF without depth ambiguity. Additionally, we propose a reconstruction algorithm based on the neural fields technique that addresses the inaccuracies of phase retrieval methods used to correct imaging system aberrations. This algorithm combines the accuracy of experimental PSFs with the long depth of field of computationally generated retrieved PSFs. QuadraPol PSF, combined with neural fields, significantly reduces the acquisition time of a conventional fluorescence microscope by approximately 20 times and captures a 100 mm$^3$ cubic volume in one shot. We validate the effectiveness of both our hardware and algorithm through all-in-focus imaging of bacterial colonies on sand surfaces and visualization of plant root morphology. Our approach offers a powerful tool for advancing biological research and ecological studies.