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We study the performance of CLAIRE—a diffeomorphic multi-node, multi-GPU image-registration algorithm and software—in large-scale biomedical imaging applications with billions of voxels. At such resolutions, most existing software packages for diffeomorphic image registration are prohibitively expensive. As a result, practitioners first significantly downsample the original images and then register them using existing tools. Our main contribution is an extensive analysis of the impact of downsampling on registration performance. We study this impact by comparing full-resolution registrations obtained with CLAIRE to lower resolution registrations for synthetic and real-world imaging datasets. Our results suggest that registration at full resolution can yield a superior registration quality—but not always. For example, downsampling a synthetic image from 10243 to 2563 decreases the Dice coefficient from 92% to 79%. However, the differences are less pronounced for noisy or low contrast high resolution images. CLAIRE allows us not only to register images of clinically relevant size in a few seconds but also to register images at unprecedented resolution in reasonable time. The highest resolution considered are CLARITY images of size 2816×3016×1162. To the best of our knowledge, this is the first study on image registration quality at such resolutions. 

Our work targets automated analysis to quantify the growth dynamics of a population of bacilliform bacteria. We propose an innovative approach to frame-sequence tracking of deformable-cell motion by the automated minimization of a new, specific cost functional. This minimization is implemented by dedicated Boltzmann machines (stochastic recurrent neural networks). Automated detection of cell divisions is handled similarly by successive minimizations of two cost functions, alternating the identification of children pairs and parent identification. We validate the proposed automatic cell tracking algorithm using (i) recordings of simulated cell colonies that closely mimic the growth dynamics of E. coli in microfluidic traps and (ii) real data. On a batch of 1100 simulated image frames, cell registration accuracies per frame ranged from 94.5% to 100%, with a high average. Our initial tests using experimental image sequences (i.e., real data) of E. coli colonies also yield convincing results, with a registration accuracy ranging from 90% to 100%. 

Central nervous system (CNS) tumors come with vastly heterogeneous histologic, molecular, and radiographic landscapes, rendering their precise characterization challenging. The rapidly growing fields of biophysical modeling and radiomics have shown promise in better characterizing the molecular, spatial, and temporal heterogeneity of tumors. Integrative analysis of CNS tumors, including clinically acquired multi-parametric magnetic resonance imaging (mpMRI) and the inverse problem of calibrating biophysical models to mpMRI data, assists in identifying macroscopic quantifiable tumor patterns of invasion and proliferation, potentially leading to improved ( a) detection/segmentation of tumor subregions and ( b) computer-aided diagnostic/prognostic/predictive modeling. This article presents a summary of ( a) biophysical growth modeling and simulation,( b) inverse problems for model calibration, ( c) these models' integration with imaging workflows, and ( d) their application to clinically relevant studies. We anticipate that such quantitative integrative analysis may even be beneficial in a future revision of the World Health Organization (WHO) classification for CNS tumors, ultimately improving patient survival prospects.