Fine scale hippocampus morphology variation cross 552 healthy subjects from age 20 to 80.

The cerebral cortex varies over the course of a person's life span: at birth, the surface is smooth, before becoming more bumpy (deeper sulci and thicker gyri) in middle age, and thinner in senior years. In this work, a similar phenomenon was observed on the hippocampus. It was previously believed the fine-scale morphology of the hippocampus could only be extracted only with high field scanners (7T, 9.4T); however, recent studies show that regular 3T MR scanners can be sufficient for this purpose. This finding opens the door for the study of fine hippocampal morphometry for a large amount of clinical data. In particular, a characteristic bumpy and subtle feature on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation, presents a dramatic degree of variability between individuals from very smooth to highly dentated. In this report, we propose a combined method joining deep learning and sub-pixel level set evolution to efficiently obtain fine-scale hippocampal segmentation on 552 healthy subjects. Through non-linear dentation extraction and fitting, we reveal that the bumpiness of the inferior surface of the human hippocampus has a clear temporal trend. It is bumpiest between 40 and 50 years old. This observation should be aligned with neurodevelopmental and aging stages.

The Cell Tracking Challenge: 10 years of objective benchmarking.

The Cell Tracking Challenge is an ongoing benchmarking initiative that has become a reference in cell segmentation and tracking algorithm development. Here, we present a significant number of improvements introduced in the challenge since our 2017 report. These include the creation of a new segmentation-only benchmark, the enrichment of the dataset repository with new datasets that increase its diversity and complexity, and the creation of a silver standard reference corpus based on the most competitive results, which will be of particular interest for data-hungry deep learning-based strategies. Furthermore, we present the up-to-date cell segmentation and tracking leaderboards, an in-depth analysis of the relationship between the performance of the state-of-the-art methods and the properties of the datasets and annotations, and two novel, insightful studies about the generalizability and the reusability of top-performing methods. These studies provide critical practical conclusions for both developers and users of traditional and machine learning-based cell segmentation and tracking algorithms.

Differentiable Histogram Loss Functions for Intensity-based Image-to-Image Translation.

We introduce the HueNet - a novel deep learning framework for a differentiable construction of intensity (1D) and joint (2D) histograms and present its applicability to paired and unpaired image-to-image translation problems. The key idea is an innovative technique for augmenting a generative neural network by histogram layers appended to the image generator. These histogram layers allow us to define two new histogram-based loss functions for constraining the structural appearance of the synthesized output image and its color distribution. Specifically, the color similarity loss is defined by the Earth Mover's Distance between the intensity histograms of the network output and a color reference image. The structural similarity loss is determined by the mutual information between the output and a content reference image based on their joint histogram. Although the HueNet can be applied to a variety of image-to-image translation problems, we chose to demonstrate its strength on the tasks of color transfer, exemplar-based image colorization, and edges → photo, where the colors of the output image are predefined. The code is available at https://github.com/mor-avi-aharon-bgu/HueNet.git.

Dual-Task ConvLSTM-UNet for Instance Segmentation of Weakly Annotated Microscopy Videos.

Convolutional Neural Networks (CNNs) are considered state of the art segmentation methods for biomedical images in general and microscopy sequences of living cells, in particular. The success of the CNNs is attributed to their ability to capture the structural properties of the data, which enables accommodating complex spatial structures of the cells, low contrast, and unclear boundaries. However, in their standard form CNNs do not exploit the temporal information available in time-lapse sequences, which can be crucial to separating touching and partially overlapping cell instances. In this work, we exploit cell dynamics using a novel CNN architecture which allows multi-scale spatio-temporal feature extraction. Specifically, a novel recurrent neural network (RNN) architecture is proposed based on the integration of a Convolutional Long Short Term Memory (ConvLSTM) network with the U-Net. The proposed ConvLSTM-UNet network is constructed as a dual-task network to enable training with weakly annotated data, in the form of approximate cell centers, termed markers, when the complete cells' outlines are not available. We further use the fast marching method to facilitate the partitioning of clustered cells into individual connected components. Finally, we suggest an adaptation of the method for 3D microscopy sequences without drastically increasing the computational load. The method was evaluated on the Cell Segmentation Benchmark and was ranked among the top three methods on six submitted datasets. Exploiting the proposed built-in marker estimator we also present state-of-the-art cell detection results for an additional, publicly available, weekly annotated dataset. The source code is available at https://gitlab.com/shaked0/lstmUnet.

An atlas of classifiers-a machine learning paradigm for brain MRI segmentation.

We present the Atlas of Classifiers (AoC)-a conceptually novel framework for brain MRI segmentation. The AoC is a spatial map of voxel-wise multinomial logistic regression (LR) functions learned from the labeled data. Upon convergence, the resulting fixed LR weights, a few for each voxel, represent the training dataset. It can, therefore, be considered as a light-weight learning machine, which despite its low capacity does not underfit the problem. The AoC construction is independent of the actual intensities of the test images, providing the flexibility to train it on the available labeled data and use it for the segmentation of images from different datasets and modalities. In this sense, it does not overfit the training data, as well. The proposed method has been applied to numerous publicly available datasets for the segmentation of brain MRI tissues and is shown to be robust to noise and outreach commonly used methods. Promising results were also obtained for multi-modal, cross-modality MRI segmentation. Finally, we show how AoC trained on brain MRIs of healthy subjects can be exploited for lesion segmentation of multiple sclerosis patients.

From a deep learning model back to the brain-Identifying regional predictors and their relation to aging.

We present a Deep Learning framework for the prediction of chronological age from structural magnetic resonance imaging scans. Previous findings associate increased brain age with neurodegenerative diseases and higher mortality rates. However, the importance of brain age prediction goes beyond serving as biomarkers for neurological disorders. Specifically, utilizing convolutional neural network (CNN) analysis to identify brain regions contributing to the prediction can shed light on the complex multivariate process of brain aging. Previous work examined methods to attribute pixel/voxel-wise contributions to the prediction in a single image, resulting in "explanation maps" that were found noisy and unreliable. To address this problem, we developed an inference scheme for combining these maps across subjects, thus creating a population-based, rather than a subject-specific map. We applied this method to a CNN ensemble trained on predicting subjects' age from raw T1 brain images in a lifespan sample of 10,176 subjects. Evaluating the model on an untouched test set resulted in mean absolute error of 3.07 years and a correlation between chronological and predicted age of r = 0.98. Using the inference method, we revealed that cavities containing cerebrospinal fluid, previously found as general atrophy markers, had the highest contribution for age prediction. Comparing maps derived from different models within the ensemble allowed to assess differences and similarities in brain regions utilized by the model. We showed that this method substantially increased the replicability of explanation maps, converged with results from voxel-based morphometry age studies and highlighted brain regions whose volumetric variability correlated the most with the prediction error.

Combining white matter diffusion and geometry for tract-specific alignment and variability analysis.

We present a framework for along-tract analysis of white matter (WM) fiber bundles based on diffusion tensor imaging (DTI) and tractography. We introduce the novel concept of fiber-flux density for modeling fiber tracts' geometry, and combine it with diffusion-based measures to define vector descriptors called Fiber-Flux Diffusion Density (FFDD). The proposed model captures informative features of WM tracts at both the microscopic (diffusion-related) and macroscopic (geometry-related) scales, thus enabling improved sensitivity to subtle structural abnormalities that are not reflected by either diffusion or geometrical properties alone. A key step in this framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tracts enable meaningful inter-subject comparisons and group-wise statistical analysis. Moreover, we show that the FMM alignment can be generalized in a straight forward manner to a single-shot co-alignment of multiple fiber bundles. The proposed alignment technique is shown to outperform a well-established, commonly used DTI registration algorithm. We demonstrate the FFDD framework on the Human Connectome Project (HCP) diffusion MRI dataset, as well as on two different datasets of contact sports players. We test our method using longitudinal scans of a basketball player diagnosed with a traumatic brain injury, showing compatibility with structural MRI findings. We further perform a group study comparing mid- and post-season scans of 13 active football players exposed to repetitive head trauma, to 17 non-player control (NPC) subjects. Results reveal statistically significant FFDD differences (p-values<0.05) between the groups, as well as increased abnormalities over time at spatially-consistent locations within several major fiber tracts of football players.

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS).

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

Morphology-guided graph search for untangling objects: C. elegans analysis.

We present a novel approach for extracting cluttered objects based on their morphological properties. Specifically, we address the problem of untangling Caenorhabditis elegans clusters in high-throughput screening experiments. We represent the skeleton of each worm cluster by a sparse directed graph whose vertices and edges correspond to worm segments and their adjacencies, respectively. We then search for paths in the graph that are most likely to represent worms while minimizing overlap. The worm likelihood measure is defined on a low-dimensional feature space that captures different worm poses, obtained from a training set of isolated worms. We test the algorithm on 236 microscopy images, each containing 15 C. elegans worms, and demonstrate successful cluster untangling and high worm detection accuracy.

Joint segmentation of image ensembles via latent atlases.

Spatial priors, such as probabilistic atlases, play an important role in MRI segmentation. However, the availability of comprehensive, reliable and suitable manual segmentations for atlas construction is limited. We therefore propose a joint segmentation of corresponding, aligned structures in the entire population that does not require a probability atlas. Instead, a latent atlas, initialized by a single manual segmentation, is inferred from the evolving segmentations of the ensemble. The proposed method is based on probabilistic principles but is solved using partial differential equations (PDEs) and energy minimization criteria, We evaluate the method by segmenting 50 brain MR volumes. Segmentation accuracy for cortical and subcortical structures approaches the quality of state-of-the-art atlas-based segmentation results, suggesting that the latent atlas method is a reasonable alternative when existing atlases are not compatible with the data to be processed.