Single-shot self-supervised object detection in microscopy published in Nature Communications

LodeSTAR tracks the plankton Noctiluca scintillans. (Image by the Authors of the manuscript.)
Single-shot self-supervised particle tracking
Benjamin Midtvedt, Jesús Pineda, Fredrik Skärberg, Erik Olsén, Harshith Bachimanchi, Emelie Wesén, Elin K. Esbjörner, Erik Selander, Fredrik Höök, Daniel Midtvedt, Giovanni Volpe
Nature Communications 13, 7492 (2022)
arXiv: 2202.13546
doi: 10.1038/s41467-022-35004-y

Object detection is a fundamental task in digital microscopy, where machine learning has made great strides in overcoming the limitations of classical approaches. The training of state-of-the-art machine-learning methods almost universally relies on vast amounts of labeled experimental data or the ability to numerically simulate realistic datasets. However, experimental data are often challenging to label and cannot be easily reproduced numerically. Here, we propose a deep-learning method, named LodeSTAR (Localization and detection from Symmetries, Translations And Rotations), that learns to detect microscopic objects with sub-pixel accuracy from a single unlabeled experimental image by exploiting the inherent roto-translational symmetries of this task. We demonstrate that LodeSTAR outperforms traditional methods in terms of accuracy, also when analyzing challenging experimental data containing densely packed cells or noisy backgrounds. Furthermore, by exploiting additional symmetries we show that LodeSTAR can measure other properties, e.g., vertical position and polarizability in holographic microscopy.

Active matter in space published in npj Microgravity

Effect of gravity on matter: Sedimentation and creaming. Fv and Fg represent the viscous force and gravitational force, respectively. (Image by Authors.)
Active matter in space
Giorgio Volpe, Clemens Bechinger, Frank Cichos, Ramin Golestanian, Hartmut Löwen, Matthias Sperl and Giovanni Volpe
npj Microgravity, 8, 54 (2022)
doi: 10.1038/s41526-022-00230-7

In the last 20 years, active matter has been a highly dynamic field of research, bridging fundamental aspects of non-equilibrium thermodynamics with applications to biology, robotics, and nano-medicine. Active matter systems are composed of units that can harvest and harness energy and information from their environment to generate complex collective behaviours and forms of self-organisation. On Earth, gravity-driven phenomena (such as sedimentation and convection) often dominate or conceal the emergence of these dynamics, especially for soft active matter systems where typical interactions are of the order of the thermal energy. In this review, we explore the ongoing and future efforts to study active matter in space, where low-gravity and microgravity conditions can lift some of these limitations. We envision that these studies will help unify our understanding of active matter systems and, more generally, of far-from-equilibrium physics both on Earth and in space. Furthermore, they will also provide guidance on how to use, process and manufacture active materials for space exploration and colonisation.

Tunable critical Casimir forces counteract Casimir-Lifshitz attraction published in Nature Physics

Gold flake suspended over a functionalized gold-coated substrate. (Image by F. Schmidt.)
Tunable critical Casimir forces counteract Casimir-Lifshitz attraction
Falko Schmidt, Agnese Callegari, Abdallah Daddi-Moussa-Ider, Battulga Munkhbat, Ruggero Verre, Timur Shegai, Mikael Käll, Hartmut Löwen, Andrea Gambassi and Giovanni Volpe
Nature Physics 19, 271-278 (2023)
arXiv: 2202.10926
doi: 10.1038/s41567-022-01795-6

Casimir forces in quantum electrodynamics emerge between microscopic metallic objects because of the confinement of the vacuum electromagnetic fluctuations occurring even at zero temperature. Their generalization at finite temperature and in material media are referred to as Casimir-Lifshitz forces. These forces are typically attractive, leading to the widespread problem of stiction between the metallic parts of micro- and nanodevices. Recently, repulsive Casimir forces have been experimentally realized but their reliance on specialized materials prevents their dynamic control and thus limits their further applicability. Here, we experimentally demonstrate that repulsive critical Casimir forces, which emerge in a critical binary liquid mixture upon approaching the critical temperature, can be used to actively control microscopic and nanoscopic objects with nanometer precision. We demonstrate this by using critical Casimir forces to prevent the stiction caused by the Casimir-Lifshitz forces. We study a microscopic gold flake above a flat gold-coated substrate immersed in a critical mixture. Far from the critical temperature, stiction occurs because of dominant Casimir-Lifshitz forces. Upon approaching the critical temperature, however, we observe the emergence of repulsive critical Casimir forces that are sufficiently strong to counteract stiction. This experimental demonstration can accelerate the development of micro- and nanodevices by preventing stiction as well as providing active control and precise tunability of the forces acting between their constituent parts.

Microplankton life histories revealed by holographic microscopy and deep learning published in eLife

Tracking of microplankton by holographic optical microscopy and deep learning. (Image by H. Bachimanchi.)
Microplankton life histories revealed by holographic microscopy and deep learning
Harshith Bachimanchi, Benjamin Midtvedt, Daniel Midtvedt, Erik Selander, and Giovanni Volpe
eLife 11, e79760 (2022)
arXiv: 2202.09046
doi: 10.7554/eLife.79760

The marine microbial food web plays a central role in the global carbon cycle. Our mechanistic understanding of the ocean, however, is biased towards its larger constituents, while rates and biomass fluxes in the microbial food web are mainly inferred from indirect measurements and ensemble averages. Yet, resolution at the level of the individual microplankton is required to advance our understanding of the oceanic food web. Here, we demonstrate that, by combining holographic microscopy with deep learning, we can follow microplanktons throughout their lifespan, continuously measuring their three dimensional position and dry mass. The deep learning algorithms circumvent the computationally intensive processing of holographic data and allow rapid measurements over extended time periods. This permits us to reliably estimate growth rates, both in terms of dry mass increase and cell divisions, as well as to measure trophic interactions between species such as predation events. The individual resolution provides information about selectivity, individual feeding rates and handling times for individual microplanktons. This method is particularly useful to explore the flux of carbon through micro-zooplankton, the most important and least known group of primary consumers in the global oceans. We exemplify this by detailed descriptions of micro-zooplankton feeding events, cell divisions, and long term monitoring of single cells from division to division.

Sex differences in multilayer functional network topology over the course of aging in 37543 UK Biobank participants accepted on Network Neuroscience

Example of the 21 resting-state networks used as nodes and their positive (red) and negative connections (blue) for one of 140 the subjects included in the analyses. (Image by the Authors of the manuscript.)
Sex differences in multilayer functional network topology over the course of aging in 37543 UK Biobank participants
Mite Mijalkov, Dániel Veréb, Oveis Jamialahmadi, Anna Canal-Garcia, Emiliano Gómez-Ruiz, Didac Vidal-Piñeiro, Stefano Romeo, Giovanni Volpe, Joana B. Pereira
Network Neuroscience 1-40 (2022)
doi: 10.1162/netn_a_00286
medRxiv: 10.1101/2022.03.08.22272089

Aging is a major risk factor for cardiovascular and neurodegenerative disorders, with considerable societal and economic implications. Healthy aging is accompanied by changes in functional connectivity between and within resting-state functional networks, which have been associated with cognitive decline. However, there is no consensus on the impact of sex on these age-related functional trajectories. Here, we show that multilayer measures provide crucial information on the interaction between sex and age on network topology, allowing for better assessment of cognitive, structural, and cardiovascular risk factors that have been shown to differ between men and women, as well as providing additional insights into the genetic influences on changes in functional connectivity that occur during aging. In a large cross-sectional sample of 37543 individuals from the UK Biobank cohort, we demonstrate that such multilayer measures that capture the relationship between positive and negative connections are more sensitive to sex-related changes in the whole-brain connectivity patterns and their topological architecture throughout aging, when compared to standard connectivity and topological measures. Our findings indicate that multilayer measures contain previously unknown information on the relationship between sex and age, which opens up new avenues for research into functional brain connectivity in aging.

Playing with Active Matter on ArXiv

One exemplar of the HEXBUGS used in the experiment. (Image by the Authors of the manuscript.)
Playing with Active Matter
Angelo Barona Balda, Aykut Argun, Agnese Callegari, Giovanni Volpe
arXiv: 2209.04168

In the last 20 years, active matter has been a very successful research field, bridging the fundamental physics of nonequilibrium thermodynamics with applications in robotics, biology, and medicine. This field deals with active particles, which, differently from passive Brownian particles, can harness energy to generate complex motions and emerging behaviors. Most active-matter experiments are performed with microscopic particles and require advanced microfabrication and microscopy techniques. Here, we propose some macroscopic experiments with active matter employing commercially available toy robots, i.e., the Hexbugs. We demonstrate how they can be easily modified to perform regular and chiral active Brownian motion. We also show that Hexbugs can interact with passive objects present in their environment and, depending on their shape, set them in motion and rotation. Furthermore, we show that, by introducing obstacles in the environment, we can sort the robots based on their motility and chirality. Finally, we demonstrate the emergence of Casimir-like activity-induced attraction between planar objects in the presence of active particles in the environment.

Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer’s disease published in Nature Communications

Comparison of cluster-specific covariance matrixes with node strength. (Image by the Authors.)
Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer’s disease
Konstantinos Poulakis, Joana B. Pereira, J.-Sebastian Muehlboeck, Lars-Olof Wahlund, Örjan Smedby, Giovanni Volpe, Colin L. Masters, David Ames, Yoshiki Niimi, Takeshi Iwatsubo, Daniel Ferreira, Eric Westman, Japanese Alzheimer’s Disease Neuroimaging Initiative & Australian Imaging, Biomarkers and Lifestyle study
Nature Communications 13, 4566 (2022)
doi: 10.1038/s41467-022-32202-6

Understanding Alzheimer’s disease (AD) heterogeneity is important for understanding the underlying pathophysiological mechanisms of AD. However, AD atrophy subtypes may reflect different disease stages or biologically distinct subtypes. Here we use longitudinal magnetic resonance imaging data (891 participants with AD dementia, 305 healthy control participants) from four international cohorts, and longitudinal clustering to estimate differential atrophy trajectories from the age of clinical disease onset. Our findings (in amyloid-β positive AD patients) show five distinct longitudinal patterns of atrophy with different demographical and cognitive characteristics. Some previously reported atrophy subtypes may reflect disease stages rather than distinct subtypes. The heterogeneity in atrophy rates and cognitive decline within the five longitudinal atrophy patterns, potentially expresses a complex combination of protective/risk factors and concomitant non-AD pathologies. By alternating between the cross-sectional and longitudinal understanding of AD subtypes these analyses may allow better understanding of disease heterogeneity.

Unraveling Parkinson’s disease heterogeneity using subtypes based on multimodal data published in Parkinsonism and Related Disorders

Particular of the brain in the group comparison analysis. (Image by the Authors.)
Unraveling Parkinson’s disease heterogeneity using subtypes based on multimodal data
Franziska Albrecht, Konstantinos Poulakis, Malin Freidle, Hanna Johansson, Urban Ekman, Giovanni Volpe, Eric Westman, Joana B. Pereira, Erika Franzén
Parkinsonism and Related Disorders 102, 19-29 (2022)
doi: 10.1016/j.parkreldis.2022.07.014

Background

Parkinson’s disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables.

Methods

Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson’s disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics.

Results

Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus.

Conclusions

Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.

Dynamic live/apoptotic cell assay using phase-contrast imaging and deep learning on bioRxiv

Phase-contrast image before virtual staining. (Image by the Authors.)
Dynamic live/apoptotic cell assay using phase-contrast imaging and deep learning
Zofia Korczak, Jesús Pineda, Saga Helgadottir, Benjamin Midtvedt, Mattias Goksör, Giovanni Volpe, Caroline B. Adiels
bioRxiv: https://doi.org/10.1101/2022.07.18.500422

Chemical live/dead assay has a long history of providing information about the viability of cells cultured in vitro. The standard methods rely on imaging chemically-stained cells using fluorescence microscopy and further analysis of the obtained images to retrieve the proportion of living cells in the sample. However, such a technique is not only time-consuming but also invasive. Due to the toxicity of chemical dyes, once a sample is stained, it is discarded, meaning that longitudinal studies are impossible using this approach. Further, information about when cells start programmed cell death (apoptosis) is more relevant for dynamic studies. Here, we present an alternative method where cell images from phase-contrast time-lapse microscopy are virtually-stained using deep learning. In this study, human endothelial cells are stained live or apoptotic and subsequently counted using the self-supervised single-shot deep-learning technique (LodeSTAR). Our approach is less labour-intensive than traditional chemical staining procedures and provides dynamic live/apoptotic cell ratios from a continuous cell population with minimal impact. Further, it can be used to extract data from dense cell samples, where manual counting is unfeasible.

Neural Network Training with Highly Incomplete Datasets published in Machine Learning: Science and Technology

Working principles for training neural networks with highly incomplete dataset: vanilla (upper panel) vs GapNet (lower panel) (Image by Yu-Wei Chang.)
Neural Network Training with Highly Incomplete Datasets
Yu-Wei Chang, Laura Natali, Oveis Jamialahmadi, Stefano Romeo, Joana B. Pereira, Giovanni Volpe
Machine Learning: Science and Technology 3, 035001 (2022)
arXiV: 2107.00429
doi: 10.1088/2632-2153/ac7b69

Neural network training and validation rely on the availability of large high-quality datasets. However, in many cases only incomplete datasets are available, particularly in health care applications, where each patient typically undergoes different clinical procedures or can drop out of a study. Since the data to train the neural networks need to be complete, most studies discard the incomplete datapoints, which reduces the size of the training data, or impute the missing features, which can lead to artefacts. Alas, both approaches are inadequate when a large portion of the data is missing. Here, we introduce GapNet, an alternative deep-learning training approach that can use highly incomplete datasets. First, the dataset is split into subsets of samples containing all values for a certain cluster of features. Then, these subsets are used to train individual neural networks. Finally, this ensemble of neural networks is combined into a single neural network whose training is fine-tuned using all complete datapoints. Using two highly incomplete real-world medical datasets, we show that GapNet improves the identification of patients with underlying Alzheimer’s disease pathology and of patients at risk of hospitalization due to Covid-19. By distilling the information available in incomplete datasets without having to reduce their size or to impute missing values, GapNet will permit to extract valuable information from a wide range of datasets, benefiting diverse fields from medicine to engineering.