Michael I. Miller

Kwame S. Kutten, Joshua T. Vogelstein, Nicolas Charon et al.

The CLARITY method renders brains optically transparent to enable high-resolution imaging in the structurally intact brain. Anatomically annotating CLARITY brains is necessary for discovering which regions contain signals of interest. Manually annotating whole-brain, terabyte CLARITY images is difficult, time-consuming, subjective, and error-prone. Automatically registering CLARITY images to a pre-annotated brain atlas offers a solution, but is difficult for several reasons. Removal of the brain from the skull and subsequent storage and processing cause variable non-rigid deformations, thus compounding inter-subject anatomical variability. Additionally, the signal in CLARITY images arises from various biochemical contrast agents which only sparsely label brain structures. This sparse labeling challenges the most commonly used registration algorithms that need to match image histogram statistics to the more densely labeled histological brain atlases. The standard method is a multiscale Mutual Information B-spline algorithm that dynamically generates an average template as an intermediate registration target. We determined that this method performs poorly when registering CLARITY brains to the Allen Institute's Mouse Reference Atlas (ARA), because the image histogram statistics are poorly matched. Therefore, we developed a method (Mask-LDDMM) for registering CLARITY images, that automatically find the brain boundary and learns the optimal deformation between the brain and atlas masks. Using Mask-LDDMM without an average template provided better results than the standard approach when registering CLARITY brains to the ARA. The LDDMM pipelines developed here provide a fast automated way to anatomically annotate CLARITY images. Our code is available as open source software at http://NeuroData.io.

Ashwin De Silva, Rahul Ramesh, Lyle Ungar et al.

Learning is a process which can update decision rules, based on past experience, such that future performance improves. Traditionally, machine learning is often evaluated under the assumption that the future will be identical to the past in distribution or change adversarially. But these assumptions can be either too optimistic or pessimistic for many problems in the real world. Real world scenarios evolve over multiple spatiotemporal scales with partially predictable dynamics. Here we reformulate the learning problem to one that centers around this idea of dynamic futures that are partially learnable. We conjecture that certain sequences of tasks are not retrospectively learnable (in which the data distribution is fixed), but are prospectively learnable (in which distributions may be dynamic), suggesting that prospective learning is more difficult in kind than retrospective learning. We argue that prospective learning more accurately characterizes many real world problems that (1) currently stymie existing artificial intelligence solutions and/or (2) lack adequate explanations for how natural intelligences solve them. Thus, studying prospective learning will lead to deeper insights and solutions to currently vexing challenges in both natural and artificial intelligences.

Kwame S. Kutten, Nicolas Charon, Michael I. Miller et al.

CLARITY is a method for converting biological tissues into translucent and porous hydrogel-tissue hybrids. This facilitates interrogation with light sheet microscopy and penetration of molecular probes while avoiding physical slicing. In this work, we develop a pipeline for registering CLARIfied mouse brains to an annotated brain atlas. Due to the novelty of this microscopy technique it is impractical to use absolute intensity values to align these images to existing standard atlases. Thus we adopt a large deformation diffeomorphic approach for registering images via mutual information matching. Furthermore we show how a cascaded multi-resolution approach can improve registration quality while reducing algorithm run time. As acquired image volumes were over a terabyte in size, they were far too large for work on personal computers. Therefore the NeuroData computational infrastructure was deployed for multi-resolution storage and visualization of these images and aligned annotations on the web.