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 signifcant 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.Web of Science2071020101

Segmentation and tracking of cells and particles in time-lapse microscopy

In biology, many different kinds of microscopy are used to study cells. There are many different kinds of transmission microscopy, where light is passed through the cells, that can be used without staining or other treatments that can harm the cells. There is also fluorescence microscopy, where fluorescent proteins or dyes are placed in the cells or in parts of the cells, so that they emit light of a specific wavelength when they are illuminated with light of a different wavelength. Many fluorescence microscopes can take images on many different depths in a sample and thereby build a three-dimensional image of the sample. Fluorescence microscopy can also be used to study particles, for example viruses, inside cells. Modern microscopes often have digital cameras or other equipment to take images or record time-lapse video. When biologists perform experiments on cells, they often record image sequences or sequences of three-dimensional volumes to see how the cells behave when they are subjected to different drugs, culture substrates, or other external factors. Previously, the analysis of recorded data has often been done manually, but that is very time-consuming and the results often become subjective and hard to reproduce. Therefore there is a great need for technology for automated analysis of image sequences with cells and particles inside cells. Such technology is needed especially in biological research and drug development. But the technology could also be used clinically, for example to tailor a cancer treatment to an individual patient by evaluating different treatments on cells from a biopsy. This thesis presents algorithms to find cells and particles in images, and to calculate tracks that show how they have moved during an experiment. We have developed a complete system that can find and track cells in all commonly used imaging modalities. We selected and extended a number of existing segmentation algorithms, and thereby created a complete tool to find cell outlines. To link the segmented objects into tracks, we developed a new track linking algorithm. The algorithm adds tracks one by one using dynamic programming, and has many advantages over prior algorithms. Among other things, it is fast, it calculates tracks which are optimal for the entire image sequence, and it can handle situations where multiple cells have been segmented incorrectly as one object. To make it possible to use information about the velocities of the objects in the linking, we developed a method where the positions of the objects are preprocessed using a filter before the linking is performed. This is important for tracking of some particles inside cells and for tracking of cell nuclei in some embryos.       We have developed an open source software which contains all tools that are necessary to analyze image sequences with cells or particles. It has tools for segmentation and tracking of objects, optimization of settings, manual correction, and analysis of outlines and tracks. We developed the software together with biologists who used it in their research. The software has already been used for data analysis in a number of biology publications. Our system has also achieved outstanding performance in three international objective comparisons of systems for tracking of cells.Inom biologi används många olika typer av mikroskopi för att studera celler. Det finns många typer av genomlysningsmikroskopi, där ljus passerar genom cellerna, som kan användas utan färgning eller andra åtgärder som riskerar att skada cellerna. Det finns också fluorescensmikroskopi där fluorescerande proteiner eller färger förs in i cellerna eller i delar av cellerna, så att de emitterar ljus av en viss våglängd då de belyses med ljus av en annan våglängd. Många fluorescensmikroskop kan ta bilder på flera olika djup i ett prov och på så sätt bygga upp en tre-dimensionell bild av provet. Fluorescensmikroskopi kan även användas för att studera partiklar, som exempelvis virus, inuti celler. Moderna mikroskop har ofta digitala kameror eller liknande utrustning för att ta bilder och spela in bildsekvenser. När biologer gör experiment på celler spelar de ofta in bildsekvenser eller sekvenser av tre-dimensionella volymer för att se hur cellerna beter sig när de utsätts för olika läkemedel, odlingssubstrat, eller andra yttre faktorer. Tidigare har analysen av inspelad data ofta gjorts manuellt, men detta är mycket tidskrävande och resultaten blir ofta subjektiva och svåra att reproducera. Därför finns det ett stort behov av teknik för automatiserad analys av bildsekvenser med celler och partiklar inuti celler. Sådan teknik behövs framförallt inom biologisk forskning och utveckling av läkemedel. Men tekniken skulle också kunna användas kliniskt, exempelvis för att skräddarsy en cancerbehandling till en enskild patient genom att utvärdera olika behandlingar på celler från en biopsi. I denna avhandling presenteras algoritmer för att hitta celler och partiklar i bilder, och för att beräkna trajektorier som visar hur de har förflyttat sig under ett experiment. Vi har utvecklat ett komplett system som kan hitta och följa celler i alla vanligt förekommande typer av mikroskopi. Vi valde ut och vidareutvecklade ett antal existerande segmenteringsalgoritmer, och skapade på så sätt ett heltäckande verktyg för att hitta cellkonturer. För att länka ihop de segmenterade objekten till trajektorier utvecklade vi en ny länkningsalgoritm. Algoritmen lägger till trajektorier en och en med hjälp av dynamisk programmering, och har många fördelar jämfört med tidigare algoritmer. Bland annat är den snabb, den beräknar trajektorier som är optimala över hela bildsekvensen, och den kan hantera fall då flera celler felaktigt segmenterats som ett objekt. För att kunna använda information om objektens hastighet vid länkningen utvecklade vi en metod där objektens positioner förbehandlas med hjälp av ett filter innan länkningen utförs. Detta är betydelsefullt för följning av vissa partiklar inuti celler och för följning av cellkärnor i vissa embryon. Vi har utvecklat en mjukvara med öppen källkod, som innehåller alla verktyg som krävs för att analysera bildsekvenser med celler eller partiklar. Den har verktyg för segmentering och följning av objekt, optimering av inställningar, manuell korrektion, och analys av konturer och trajektorier. Vi utvecklade mjukvaran i samarbete med biologer som använde den i sin forskning. Mjukvaran har redan använts för dataanalys i ett antal biologiska publikationer. Vårt system har även uppnått enastående resultat i tre internationella objektiva jämförelser av system för följning av celler.QC 20161125</p

Global linking of cell tracks using the Viterbi algorithm

Automated tracking of living cells in microscopy image sequences is an important and challenging problem. With this application in mind, we propose a global track linking algorithm, which links cell outlines generated by a segmentation algorithm into tracks. The algorithm adds tracks to the image sequence one at a time, in a way which uses information from the complete image sequence in every linking decision. This is achieved by finding the tracks which give the largest possible increases to a probabilistically motivated scoring function, using the Viterbi algorithm. We also present a novel way to alter previously created tracks when new tracks are created, thus mitigating the effects of error propagation. The algorithm can handle mitosis, apoptosis, and migration in and out of the imaged area, and can also deal with false positives, missed detections, and clusters of jointly segmented cells. The algorithm performance is demonstrated on two challenging datasets acquired using bright-field microscopy, but in principle, the algorithm can be used with any cell type and any imaging technique, presuming there is a suitable segmentation algorithm.QC 20150518</p

Global linking of cell tracks using the Viterbi algorithm

Automated tracking of living cells in microscopy image sequences is an important and challenging problem. With this application in mind, we propose a global track linking algorithm, which links cell outlines generated by a segmentation algorithm into tracks. The algorithm adds tracks to the image sequence one at a time, in a way which uses information from the complete image sequence in every linking decision. This is achieved by finding the tracks which give the largest possible increases to a probabilistically motivated scoring function, using the Viterbi algorithm. We also present a novel way to alter previously created tracks when new tracks are created, thus mitigating the effects of error propagation. The algorithm can handle mitosis, apoptosis, and migration in and out of the imaged area, and can also deal with false positives, missed detections, and clusters of jointly segmented cells. The algorithm performance is demonstrated on two challenging datasets acquired using bright-field microscopy, but in principle, the algorithm can be used with any cell type and any imaging technique, presuming there is a suitable segmentation algorithm.QC 20150518</p

Optimal Scheduling for Interference Mitigation by Range Information

This paper describes several algorithms for generating an optimal schedule for multiple access on a shared channel by utilizing range information in a fully connected network. We also provide detailed analysis for the proposed algorithms in terms of their complexity, convergence, and effect of non-idealities in the network. The performance of the proposed schemes are compared with non-aided methods to quantify the benefits of using the range information in the communication. We argue that the proposed techniques yield significant benefits as the number of nodes in the network increases. We provide simulation results in support of the claim. The proposed methods indicate that the throughput can be increased on average by 3-10 times for typical network configurations.QS 2016</p

Optimal Scheduling for Interference Mitigation by Range Information

This paper describes several algorithms for generating an optimal schedule for multiple access on a shared channel by utilizing range information in a fully connected network. We also provide detailed analysis for the proposed algorithms in terms of their complexity, convergence, and effect of non-idealities in the network. The performance of the proposed schemes are compared with non-aided methods to quantify the benefits of using the range information in the communication. We argue that the proposed techniques yield significant benefits as the number of nodes in the network increases. We provide simulation results in support of the claim. The proposed methods indicate that the throughput can be increased on average by 3-10 times for typical network configurations.QS 2016</p

Optimal Scheduling for Interference Mitigation by Range Information

This paper describes several algorithms for generating an optimal schedule for multiple access on a shared channel by utilizing range information in a fully connected network. We also provide detailed analysis for the proposed algorithms in terms of their complexity, convergence, and effect of non-idealities in the network. The performance of the proposed schemes are compared with non-aided methods to quantify the benefits of using the range information in the communication. We argue that the proposed techniques yield significant benefits as the number of nodes in the network increases. We provide simulation results in support of the claim. The proposed methods indicate that the throughput can be increased on average by 3-10 times for typical network configurations.QS 2016</p