Institute of Fundamental Technological Research

Segmentation of biomedical images is often ambiguous and complicated by noise, varying
contrasts, and imaging artifacts. We address the challenge of segmenting images of brain
tissue in which gene expression has been localized using in situ hybridization. Since gene
expression patterns differ widely between genes, it can be difficult to correctly discriminate
pixels positive for gene expression. In testing different segmentation networks, we observed
that each network had its own trade-offs between sensitivity and precision. To exploit
the benefits of all trained networks, we developed a meta-network that learns to combine
multiple segmentation maps from diverse segmentation architectures to generate a final
segmentation that best matches the ground-truth label. In our experiments, the meta-
network outperforms ensembles that simply average segmentation maps.

meta-learning, segmentation, gene expression

We present the first automated pipeline to create an atlas of in situ hybridization gene expression in the adult marmoset brain in the same stereotaxic space. The pipeline consists of segmentation of gene expression from microscopy images and registration of images to a standard space. Automation of this pipeline is necessary to analyze the large volume of data in the genome-wide whole-brain dataset, and to process images that have varying intensity profiles and expression patterns with minimal human bias. To reduce the number of labelled images required for training, we develop a semi-supervised segmentation model. We further develop an iterative algorithm to register images to a standard space, enabling comparative analysis between genes and concurrent visualization with other datasets, thereby facilitating a more holistic understanding of primate brain structure and function.

contrastive learning, gene atlas, segmen-tation, semi-supervised learning, registration

We propose a novel image registration method based on implicit neural representations that addresses the challenging problem of registering a pair of brain images with similar anatomical structures, but where one image contains additional features or artifacts that are not present in the other image. To demonstrate its effectiveness, we use 2D microscopy in situ hybridization gene expression images of the marmoset brain. Accurately quantifying gene expression requires image registration to a brain template, which is difficult due to the diversity of patterns causing variations in visible anatomical brain structures. Our approach uses implicit networks in combination with an image exclusion loss to jointly perform the registration and decompose the image into a support and residual image. The support image aligns well with the template, while the residual image captures individual image characteristics that diverge from the template. In experiments, our method provided excellent results and outperformed other registration techniques.

brain, deep learning, gene expression, implicit neural representations, registration