KEYWORDS: Lawrencium, Image resolution, Super resolution, Convolutional neural networks, Cancer, Scanners, Data modeling, Image segmentation, Convolution, Signal to noise ratio
We study a problem scenario of super-resolution (SR) algorithms in the context of whole slide imaging (WSI), a popular imaging modality in digital pathology. Instead of just one pair of high- and low-resolution images, which is typically the setup in which SR algorithms are designed, we are given multiple intermediate resolutions of the same image as well. The question remains how to best utilize such data to make the transformation learning problem inherent to SR more tractable and address the unique challenges that arises in this biomedical application. We propose a recurrent convolutional neural network model, to generate SR images from such multi-resolution WSI datasets. Specifically, we show that having such intermediate resolutions is highly effective in making the learning problem easily trainable and address large resolution difference in the low and high-resolution images common in WSI, even without the availability of a large size training data. Experimental results show state-of-the-art performance on three WSI histopathology cancer datasets, across a number of metrics.
Collagen organization plays an integral role in many diseases including cancer. Here we introduce a low-cost, open-access collagen imaging and image analysis platform for quantifying fibrillar collagen organization. LC-PolScope was used as the imaging modality that incorporates a precision universal compensator made of two computer controlled liquid crystal variable retarders. This imaging system can be easily implemented on standard microscopes as a cost-effective alternative to second harmonic generation (SHG) imaging and staining on a wide range of available pathology slide formats, including the most commonly used H&E stained slides. In the collagen image analysis, a two-step registration process was first used for overlaying bright-field images on polarized images of collagen: 1) Extract collagenous stroma from H&E bright-field images by image segmentation in HSV color space and performing color separation using K-means clustering algorithm to find the best collagen estimate; 2) Use an iterative intensity-based image registration algorithm to find the affine transform that registers the collagen extracted image to the SHG image at different resolutions. Then, the registered bright field H&E image was used as a guide to evaluate collagen organization near any biological structure such as blood vessels, tumors etc. These algorithms have been implemented in our open source collagen analysis software tool “CurveAlign” package that has been widely used for collagen feature extraction, including detection of tumor associated collagen signatures. As a proof of concept, we are now using this platform to investigate collagen organization in metastatic pancreatic cancer vs non-metastatic pancreatic cancer.
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