Biology-driven assessment of deep learning super-resolution imaging of the porosity network in dentin

The mechanosensory system of teeth is currently believed to partly rely on Odontoblast cells stimulation by fluid flow through a porosity network extending through dentin. Visualizing the smallest sub-microscopic porosity vessels therefore requires the highest achievable resolution from confocal fluorescence microscopy, the current gold standard. This considerably limits the extent of the field of view to very small sample regions. To overcome this limitation, we tested different deep learning (DL) super-resolution (SR) models to allow faster experimental acquisitions of lower resolution images and restore optimal image quality by post-processing. Three supervised 2D SR models (RCAN, pix2pix, FSRCNN) and one unsupervised (CycleGAN) were applied to a unique set of experimentally paired high- and low-resolution confocal images acquired with different sampling schemes, resulting in a pixel size increase of x2, x4, x8. Model performance was quantified using a broad set of similarity and distribution-based image quality assessment (IQA) metrics, which yielded inconsistent results that mostly contradicted our visual perception. This raises the question of the relevance of such generic metrics to efficiently target the specific structure of dental porosity. To resolve this conflicting information, the generated SR images were segmented taking into account the specific scales and morphology of the porosity network and analysed by comparing connected components. Additionally, the capacity of the SR models to preserve 3D porosity connectivity throughout the confocal image stacks was evaluated using graph analysis. This biology-driven assessment allowed a far better mechanistic interpretation of SR performance, highlighting differences in model sensitivity to weak intensity features and the impact of non-linearity in image generation, which explains the failure of standard IQA metrics.