Highlights 29 30• TIRL: new framework for prototyping bespoke image registration pipelines 31• Pipeline for automated registration of small-slide histology to whole-brain MRI 32• Slice-to-volume registration accounting for through-plane deformations 33• No need for serial histological sampling 34
35Abstract 36 37 There is a need to understand the histopathological basis of MRI signal characteristics in 38 complex biological matter. Microstructural imaging holds promise for sensitive and specific 39 indicators of the early stages of human neurodegeneration but requires validation against 40 traditional histological markers before it can be reliably applied in the clinical setting. 41Validation relies on a precise and preferably automatic method to align MRI and histological 42 images of the same tissue, which poses unique challenges compared to more conventional 43 MRI-to-MRI registration. 44
45A customisable open-source platform, Tensor Image Registration Library (TIRL) is presented. 46Based on TIRL, a fully automated pipeline was implemented to align small stained histological 47
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