On the multiscale dynamics of punctuated evolution.

For five decades, paleontologists, paleobiologists, and ecologists have investigated patterns of punctuated equilibria in biology. Here, we step outside those fields and summarize recent advances in the theory of and evidence for punctuated equilibria, gathered from contemporary observations in geology, molecular biology, genetics, anthropology, and sociotechnology. Taken in the aggregate, these observations lead to a more general theory that we refer to as punctuated evolution. The quality of recent datasets is beginning to illustrate the mechanics of punctuated evolution in a way that can be modeled across a vast range of phenomena, from mass extinctions hundreds of millions of years ago to the possible future ahead in the Anthropocene. We expect the study of punctuated evolution to be applicable beyond biological scenarios.

Punctuated equilibrium at 50: Anything there for evolutionary anthropology? Yes; definitely.

The theory of punctuated equilibrium (PE) was developed a little over 50 years ago to explain long-term, large-scale appearance and disappearance of species in the fossil record. A theory designed specifically for that purpose cannot be expected, out of the box, to be directly applicable to biocultural evolution, but in revised form, PE offers a promising approach to incorporating not only a wealth of recent empirical research on genetic, linguistic, and technological evolution but also large databases that document human biological and cultural diversity across time and space. Here we isolate the fundamental components of PE and propose which pieces, when reassembled or renamed, can be highly useful in evolutionary anthropology, especially as humanity faces abrupt ecological challenges on an increasingly larger scale.

Composition, structure and robustness of Lichen guilds.

Symbiosis is a major engine of evolutionary innovation underlying many extant complex organisms. Lichens are a paradigmatic example that offers a unique perspective on the role of symbiosis in ecological success and evolutionary diversification. Lichen studies have produced a wealth of information regarding the importance of symbiosis, but they frequently focus on a few species, limiting our understanding of large-scale phenomena such as guilds. Guilds are groupings of lichens that assist each other's proliferation and are intimately linked by a shared set of photobionts, constituting an extensive network of relationships. To characterize the network of lichen symbionts, we used a large data set ([Formula: see text] publications) of natural photobiont-mycobiont associations. The entire lichen network was found to be modular, but this organization does not directly match taxonomic information in the data set, prompting a reconsideration of lichen guild structure and composition. The multiscale nature of this network reveals that the major lichen guilds are better represented as clusters with several substructures rather than as monolithic communities. Heterogeneous guild structure fosters robustness, with keystone species functioning as bridges between guilds and whose extinction would endanger global stability.

Minimizing the effect of white matter lesions on deep learning based tissue segmentation for brain volumetry.

Automated methods for segmentation-based brain volumetry may be confounded by the presence of white matter (WM) lesions, which introduce abnormal intensities that can alter the classification of not only neighboring but also distant brain tissue. These lesions are common in pathologies where brain volumetry is also an important prognostic marker, such as in multiple sclerosis (MS), and thus reducing their effects is critical for improving volumetric accuracy and reliability. In this work, we analyze the effect of WM lesions on deep learning based brain tissue segmentation methods for brain volumetry and introduce techniques to reduce the error these lesions produce on the measured volumes. We propose a 3D patch-based deep learning framework for brain tissue segmentation which is trained on the outputs of a reference classical method. To deal more robustly with pathological cases having WM lesions, we use a combination of small patches and a percentile-based input normalization. To minimize the effect of WM lesions, we also propose a multi-task double U-Net architecture performing end-to-end inpainting and segmentation, along with a training data generation procedure. In the evaluation, we first analyze the error introduced by artificial WM lesions on our framework as well as in the reference segmentation method without the use of lesion inpainting techniques. To the best of our knowledge, this is the first analysis of WM lesion effect on a deep learning based tissue segmentation approach for brain volumetry. The proposed framework shows a significantly smaller and more localized error introduced by WM lesions than the reference segmentation method, that displays much larger global differences. We also evaluated the proposed lesion effect minimization technique by comparing the measured volumes before and after introducing artificial WM lesions to healthy images. The proposed approach performing end-to-end inpainting and segmentation effectively reduces the error introduced by small and large WM lesions in the resulting volumetry, obtaining absolute volume differences of 0.01 ± 0.03% for GM and 0.02 ± 0.04% for WM. Increasing the accuracy and reliability of automated brain volumetry methods will reduce the sample size needed to establish meaningful correlations in clinical studies and allow its use in individualized assessments as a diagnostic and prognostic marker for neurodegenerative pathologies.

A cultural evolutionary theory that explains both gradual and punctuated change.

Cumulative cultural evolution (CCE) occurs among humans who may be presented with many similar options from which to choose, as well as many social influences and diverse environments. It is unknown what general principles underlie the wide range of CCE dynamics and whether they can all be explained by the same unified paradigm. Here, we present a scalable evolutionary model of discrete choice with social learning, based on a few behavioural science assumptions. This paradigm connects the degree of transparency in social learning to the human tendency to imitate others. Computer simulations and quantitative analysis show the interaction of three primary factors-information transparency, popularity bias and population size-drives the pace of CCE. The model predicts a stable rate of evolutionary change for modest degrees of popularity bias. As popularity bias grows, the transition from gradual to punctuated change occurs, with maladaptive subpopulations arising on their own. When the popularity bias gets too severe, CCE stops. This provides a consistent framework for explaining the rich and complex adaptive dynamics taking place in the real world, such as modern digital media.

Evaluating the use of synthetic T1-w images in new T2 lesion detection in multiple sclerosis.

The assessment of disease activity using serial brain MRI scans is one of the most valuable strategies for monitoring treatment response in patients with multiple sclerosis (MS) receiving disease-modifying treatments. Recently, several deep learning approaches have been proposed to improve this analysis, obtaining a good trade-off between sensitivity and specificity, especially when using T1-w and T2-FLAIR images as inputs. However, the need to acquire two different types of images is time-consuming, costly and not always available in clinical practice. In this paper, we investigate an approach to generate synthetic T1-w images from T2-FLAIR images and subsequently analyse the impact of using original and synthetic T1-w images on the performance of a state-of-the-art approach for longitudinal MS lesion detection. We evaluate our approach on a dataset containing 136 images from MS patients, and 73 images with lesion activity (the appearance of new T2 lesions in follow-up scans). To evaluate the synthesis of the images, we analyse the structural similarity index metric and the median absolute error and obtain consistent results. To study the impact of synthetic T1-w images, we evaluate the performance of the new lesion detection approach when using (1) both T2-FLAIR and T1-w original images, (2) only T2-FLAIR images, and (3) both T2-FLAIR and synthetic T1-w images. Sensitivities of 0.75, 0.63, and 0.81, respectively, were obtained at the same false-positive rate (0.14) for all experiments. In addition, we also present the results obtained when using the data from the international MSSEG-2 challenge, showing also an improvement when including synthetic T1-w images. In conclusion, we show that the use of synthetic images can support the lack of data or even be used instead of the original image to homogenize the contrast of the different acquisitions in new T2 lesions detection algorithms.

Ecological network complexity scales with area.

Larger geographical areas contain more species-an observation raised to a law in ecology. Less explored is whether biodiversity changes are accompanied by a modification of interaction networks. We use data from 32 spatial interaction networks from different ecosystems to analyse how network structure changes with area. We find that basic community structure descriptors (number of species, links and links per species) increase with area following a power law. Yet, the distribution of links per species varies little with area, indicating that the fundamental organization of interactions within networks is conserved. Our null model analyses suggest that the spatial scaling of network structure is determined by factors beyond species richness and the number of links. We demonstrate that biodiversity-area relationships can be extended from species counts to higher levels of network complexity. Therefore, the consequences of anthropogenic habitat destruction may extend from species loss to wider simplification of natural communities.

Assessment of automatic decision-support systems for detecting active T2 lesions in multiple sclerosis patients.

BACKGROUND: Active (new/enlarging) T2 lesion counts are routinely used in the clinical management of multiple sclerosis. Thus, automated tools able to accurately identify active T2 lesions would be of high interest to neuroradiologists for assisting in their clinical activity. OBJECTIVE: To compare the accuracy in detecting active T2 lesions and of radiologically active patients based on different visual and automated methods. METHODS: One hundred multiple sclerosis patients underwent two magnetic resonance imaging examinations within 12 months. Four approaches were assessed for detecting active T2 lesions: (1) conventional neuroradiological reports; (2) prospective visual analyses performed by an expert; (3) automated unsupervised tool; and (4) supervised convolutional neural network. As a gold standard, a reference outcome was created by the consensus of two observers. RESULTS: The automated methods detected a higher number of active T2 lesions, and a higher number of active patients, but a higher number of false-positive active patients than visual methods. The convolutional neural network model was more sensitive in detecting active T2 lesions and active patients than the other automated method. CONCLUSION: Automated convolutional neural network models show potential as an aid to neuroradiological assessment in clinical practice, although visual supervision of the outcomes is still required.

Assessing the Accuracy and Reproducibility of PARIETAL: A Deep Learning Brain Extraction Algorithm.

BACKGROUND: Manual brain extraction from magnetic resonance (MR) images is time-consuming and prone to intra- and inter-rater variability. Several automated approaches have been developed to alleviate these constraints, including deep learning pipelines. However, these methods tend to reduce their performance in unseen magnetic resonance imaging (MRI) scanner vendors and different imaging protocols. PURPOSE: To present and evaluate for clinical use PARIETAL, a pre-trained deep learning brain extraction method. We compare its reproducibility in a scan/rescan analysis and its robustness among scanners of different manufacturers. STUDY TYPE: Retrospective. POPULATION: Twenty-one subjects (12 women) with age range 22-48 years acquired using three different MRI scanner machines including scan/rescan in each of them. FIELD STRENGTH/SEQUENCE: T1-weighted images acquired in a 3-T Siemens with magnetization prepared rapid gradient-echo sequence and two 1.5 T scanners, Philips and GE, with spin-echo and spoiled gradient-recalled (SPGR) sequences, respectively. ASSESSMENT: Analysis of the intracranial cavity volumes obtained for each subject on the three different scanners and the scan/rescan acquisitions. STATISTICAL TESTS: Parametric permutation tests of the differences in volumes to rank and statistically evaluate the performance of PARIETAL compared to state-of-the-art methods. RESULTS: The mean absolute intracranial volume differences obtained by PARIETAL in the scan/rescan analysis were 1.88 mL, 3.91 mL, and 4.71 mL for Siemens, GE, and Philips scanners, respectively. PARIETAL was the best-ranked method on Siemens and GE scanners, while decreasing to Rank 2 on the Philips images. Intracranial differences for the same subject between scanners were 5.46 mL, 27.16 mL, and 30.44 mL for GE/Philips, Siemens/Philips, and Siemens/GE comparison, respectively. The permutation tests revealed that PARIETAL was always in Rank 1, obtaining the most similar volumetric results between scanners. DATA CONCLUSION: PARIETAL accurately segments the brain and it generalizes to images acquired at different sites without the need of training or fine-tuning it again. PARIETAL is publicly available. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Transductive Transfer Learning for Domain Adaptation in Brain Magnetic Resonance Image Segmentation.

Segmentation of brain images from Magnetic Resonance Images (MRI) is an indispensable step in clinical practice. Morphological changes of sub-cortical brain structures and quantification of brain lesions are considered biomarkers of neurological and neurodegenerative disorders and used for diagnosis, treatment planning, and monitoring disease progression. In recent years, deep learning methods showed an outstanding performance in medical image segmentation. However, these methods suffer from generalisability problem due to inter-centre and inter-scanner variabilities of the MRI images. The main objective of the study is to develop an automated deep learning segmentation approach that is accurate and robust to the variabilities in scanner and acquisition protocols. In this paper, we propose a transductive transfer learning approach for domain adaptation to reduce the domain-shift effect in brain MRI segmentation. The transductive scenario assumes that there are sets of images from two different domains: (1) source-images with manually annotated labels; and (2) target-images without expert annotations. Then, the network is jointly optimised integrating both source and target images into the transductive training process to segment the regions of interest and to minimise the domain-shift effect. We proposed to use a histogram loss in the feature level to carry out the latter optimisation problem. In order to demonstrate the benefit of the proposed approach, the method has been tested in two different brain MRI image segmentation problems using multi-centre and multi-scanner databases for: (1) sub-cortical brain structure segmentation; and (2) white matter hyperintensities segmentation. The experiments showed that the segmentation performance of a pre-trained model could be significantly improved by up to 10%. For the first segmentation problem it was possible to achieve a maximum improvement from 0.680 to 0.799 in average Dice Similarity Coefficient (DSC) metric and for the second problem the average DSC improved from 0.504 to 0.602. Moreover, the improvements after domain adaptation were on par or showed better performance compared to the commonly used traditional unsupervised segmentation methods (FIRST and LST), also achieving faster execution time. Taking this into account, this work presents one more step toward the practical implementation of deep learning algorithms into the clinical routine.

Generating Longitudinal Atrophy Evaluation Datasets on Brain Magnetic Resonance Images Using Convolutional Neural Networks and Segmentation Priors.

Brain atrophy quantification plays a fundamental role in neuroinformatics since it permits studying brain development and neurological disorders. However, the lack of a ground truth prevents testing the accuracy of longitudinal atrophy quantification methods. We propose a deep learning framework to generate longitudinal datasets by deforming T1-w brain magnetic resonance imaging scans as requested through segmentation maps. Our proposal incorporates a cascaded multi-path U-Net optimised with a multi-objective loss which allows its paths to generate different brain regions accurately. We provided our model with baseline scans and real follow-up segmentation maps from two longitudinal datasets, ADNI and OASIS, and observed that our framework could produce synthetic follow-up scans that matched the real ones (Total scans= 584; Median absolute error: 0.03 ± 0.02; Structural similarity index: 0.98 ± 0.02; Dice similarity coefficient: 0.95 ± 0.02; Percentage of brain volume change: 0.24 ± 0.16; Jacobian integration: 1.13 ± 0.05). Compared to two relevant works generating brain lesions using U-Nets and conditional generative adversarial networks (CGAN), our proposal outperformed them significantly in most cases (p < 0.01), except in the delineation of brain edges where the CGAN took the lead (Jacobian integration: Ours - 1.13 ± 0.05 vs CGAN - 1.00 ± 0.02; p < 0.01). We examined whether changes induced with our framework were detected by FAST, SPM, SIENA, SIENAX, and the Jacobian integration method. We observed that induced and detected changes were highly correlated (Adj. R2 > 0.86). Our preliminary results on harmonised datasets showed the potential of our framework to be applied to various data collections without further adjustment.

Acute and sub-acute stroke lesion segmentation from multimodal MRI.

BACKGROUND AND OBJECTIVE: Acute stroke lesion segmentation tasks are of great clinical interest as they can help doctors make better informed time-critical treatment decisions. Magnetic resonance imaging (MRI) is time demanding but can provide images that are considered the gold standard for diagnosis. Automated stroke lesion segmentation can provide with an estimate of the location and volume of the lesioned tissue, which can help in the clinical practice to better assess and evaluate the risks of each treatment. METHODS: We propose a deep learning methodology for acute and sub-acute stroke lesion segmentation using multimodal MR imaging. We pre-process the data to facilitate learning features based on the symmetry of brain hemispheres. The issue of class imbalance is tackled using small patches with a balanced training patch sampling strategy and a dynamically weighted loss function. Moreover, a combination of whole patch predictions, using a U-Net based CNN architecture, and high degree of overlapping patches reduces the need for additional post-processing. RESULTS: The proposed method is evaluated using two public datasets from the 2015 Ischemic Stroke Lesion Segmentation challenge (ISLES 2015). These involve the tasks of sub-acute stroke lesion segmentation (SISS) and acute stroke penumbra estimation (SPES) from multiple diffusion, perfusion and anatomical MRI modalities. The performance is compared against state-of-the-art methods with a blind online testing set evaluation on each of the challenges. At the time of submitting this manuscript, our approach is the first method in the online rankings for the SISS (DSC=0.59 ± 0.31) and SPES sub-tasks (DSC=0.84 ± 0.10). When compared with the rest of submitted strategies, we achieve top rank performance with a lower Hausdorff distance. CONCLUSIONS: Better segmentation results are obtained by leveraging the anatomy and pathophysiology of acute stroke lesions and using a combined approach to minimize the effects of class imbalance. The same training procedure is used for both tasks, showing the proposed methodology can generalize well enough to deal with different unrelated tasks and imaging modalities without hyper-parameter tuning. In order to promote the reproducibility of our results, a public version of the proposed method has been released to the scientific community.

Mapping co-ancestry connections between the genome of a Medieval individual and modern Europeans.

Historical genetic links among similar populations can be difficult to establish. Identity by descent (IBD) analyses find genomic blocks that represent direct genealogical relationships among individuals. However, this method has rarely been applied to ancient genomes because IBD stretches are progressively fragmented by recombination and thus not recognizable after few tens of generations. To explore such genealogical relationships, we estimated long IBD blocks among modern Europeans, generating networks to uncover the genetic structures. We found that Basques, Sardinians, Icelanders and Orcadians form, each of them, highly intraconnected sub-clusters in a European network, indicating dense genealogical links within small, isolated populations. We also exposed individual genealogical links -such as the connection between one Basque and one Icelandic individual- that cannot be uncovered with other, widely used population genetics methods such as PCA or ADMIXTURE. Moreover, using ancient DNA technology we sequenced a Late Medieval individual (Barcelona, Spain) to high genomic coverage and identified IBD blocks shared between her and modern Europeans. The Medieval IBD blocks are statistically overrepresented only in modern Spaniards, which is the geographically closest population. This approach can be used to produce a fine-scale reflection of shared ancestry across different populations of the world, offering a direct genetic link from the past to the present.

Coexistence of nestedness and modularity in host-pathogen infection networks.

The long-term coevolution of hosts and pathogens in their environment forms a complex web of multi-scale interactions. Understanding how environmental heterogeneity affects the structure of host-pathogen networks is a prerequisite for predicting disease dynamics and emergence. Although nestedness is common in ecological networks, and theory suggests that nested ecosystems are less prone to dynamic instability, why nestedness varies in time and space is not fully understood. Many studies have been limited by a focus on single habitats and the absence of a link between spatial variation and structural heterogeneity such as nestedness and modularity. Here we propose a neutral model for the evolution of host-pathogen networks in multiple habitats. In contrast to previous studies, our study proposes that local modularity can coexist with global nestedness, and shows that real ecosystems are found in a continuum between nested-modular and nested networks driven by intraspecific competition. Nestedness depends on neutral mechanisms of community assembly, whereas modularity is contingent on local adaptation and competition. The structural pattern may change spatially and temporally but remains stable over evolutionary timescales. We validate our theoretical predictions with a longitudinal study of plant-virus interactions in a heterogeneous agricultural landscape.

Evolving complexity: how tinkering shapes cells, software and ecological networks.

A common trait of complex systems is that they can be represented by means of a network of interacting parts. It is, in fact, the network organization (more than the parts) that largely conditions most higher-level properties, which are not reducible to the properties of the individual parts. Can the topological organization of these webs provide some insight into their evolutionary origins? Both biological and artificial networks share some common architectural traits. They are often heterogeneous and sparse, and most exhibit different types of correlations, such as nestedness, modularity or hierarchical patterns. These properties have often been attributed to the selection of functionally meaningful traits. However, a proper formulation of generative network models suggests a rather different picture. Against the standard selection-optimization argument, some networks reveal the inevitable generation of complex patterns resulting from reuse and can be modelled using duplication-rewiring rules lacking functionality. These give rise to the observed heterogeneous, scale-free and modular architectures. Here, we examine the evidence for tinkering in cellular, technological and ecological webs and its impact in shaping their architecture. Our analysis suggests a serious consideration of the role played by selection as the origin of network topology. Instead, we suggest that the amplification processes associated with reuse might shape these graphs at the topological level. In biological systems, selection forces would take advantage of emergent patterns. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'.

A fully convolutional neural network for new T2-w lesion detection in multiple sclerosis.

INTRODUCTION: Longitudinal magnetic resonance imaging (MRI) has an important role in multiple sclerosis (MS) diagnosis and follow-up. Specifically, the presence of new T2-w lesions on brain MR scans is considered a predictive biomarker for the disease. In this study, we propose a fully convolutional neural network (FCNN) to detect new T2-w lesions in longitudinal brain MR images. METHODS: One year apart, multichannel brain MR scans (T1-w, T2-w, PD-w, and FLAIR) were obtained for 60 patients, 36 of them with new T2-w lesions. Modalities from both temporal points were preprocessed and linearly coregistered. Afterwards, an FCNN, whose inputs were from the baseline and follow-up images, was trained to detect new MS lesions. The first part of the network consisted of U-Net blocks that learned the deformation fields (DFs) and nonlinearly registered the baseline image to the follow-up image for each input modality. The learned DFs together with the baseline and follow-up images were then fed to the second part, another U-Net that performed the final detection and segmentation of new T2-w lesions. The model was trained end-to-end, simultaneously learning both the DFs and the new T2-w lesions, using a combined loss function. We evaluated the performance of the model following a leave-one-out cross-validation scheme. RESULTS: In terms of the detection of new lesions, we obtained a mean Dice similarity coefficient of 0.83 with a true positive rate of 83.09% and a false positive detection rate of 9.36%. In terms of segmentation, we obtained a mean Dice similarity coefficient of 0.55. The performance of our model was significantly better compared to the state-of-the-art methods (p < 0.05). CONCLUSIONS: Our proposal shows the benefits of combining a learning-based registration network with a segmentation network. Compared to other methods, the proposed model decreases the number of false positives. During testing, the proposed model operates faster than the other two state-of-the-art methods based on the DF obtained by Demons.

Acute ischemic stroke lesion core segmentation in CT perfusion images using fully convolutional neural networks.

The use of Computed Tomography (CT) imaging for patients with stroke symptoms is an essential step for triaging and diagnosis in many hospitals. However, the subtle expression of ischemia in acute CT images has made it hard for automated methods to extract potentially quantifiable information. In this work, we present and evaluate an automated deep learning tool for acute stroke lesion core segmentation from CT and CT perfusion images. For evaluation, the Ischemic Stroke Lesion Segmentation (ISLES) 2018 challenge dataset is used that includes 94 cases for training and 62 for testing. The presented method is an improved version of our workshop challenge approach that was ranked among the workshop challenge finalists. The introduced contributions include a more regularized network training procedure, symmetric modality augmentation and uncertainty filtering. Each of these steps is quantitatively evaluated by cross-validation on the training set. Moreover, our proposal is evaluated against other state-of-the-art methods with a blind testing set evaluation using the challenge website, which maintains an ongoing leaderboard for fair and direct method comparison. The tool reaches competitive performance ranking among the top performing methods of the ISLES 2018 testing leaderboard with an average Dice similarity coefficient of 49%. In the clinical setting, this method can provide an estimate of lesion core size and location without performing time costly magnetic resonance imaging. The presented tool is made publicly available for the research community.

Supervised Domain Adaptation for Automatic Sub-cortical Brain Structure Segmentation with Minimal User Interaction.

In recent years, some convolutional neural networks (CNNs) have been proposed to segment sub-cortical brain structures from magnetic resonance images (MRIs). Although these methods provide accurate segmentation, there is a reproducibility issue regarding segmenting MRI volumes from different image domains - e.g., differences in protocol, scanner, and intensity profile. Thus, the network must be retrained from scratch to perform similarly in different imaging domains, limiting the applicability of such methods in clinical settings. In this paper, we employ the transfer learning strategy to solve the domain shift problem. We reduced the number of training images by leveraging the knowledge obtained by a pretrained network, and improved the training speed by reducing the number of trainable parameters of the CNN. We tested our method on two publicly available datasets - MICCAI 2012 and IBSR - and compared them with a commonly used approach: FIRST. Our method showed similar results to those obtained by a fully trained CNN, and our method used a remarkably smaller number of images from the target domain. Moreover, training the network with only one image from MICCAI 2012 and three images from IBSR datasets was sufficient to significantly outperform FIRST with (p < 0.001) and (p < 0.05), respectively.

Standardized Assessment of Automatic Segmentation of White Matter Hyperintensities and Results of the WMH Segmentation Challenge.

Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained from manual segmentations on brain MR images, which is a laborious procedure. The automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their methods on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge. Sixty T1 + FLAIR images from three MR scanners were released with the manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. The segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: 1) Dice similarity coefficient; 2) modified Hausdorff distance (95th percentile); 3) absolute log-transformed volume difference; 4) sensitivity for detecting individual lesions; and 5) F1-score for individual lesions. In addition, the methods were ranked on their inter-scanner robustness; 20 participants submitted their methods for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all the methods generalize to unseen scanners. The challenge remains open for future submissions and provides a public platform for method evaluation.