Wiro J. Niessen

Automated analysis of time-lapse fluorescence microscopy images

MOTIVATIONnComplete, accurate and reproducible analysis of intracellular foci from fluorescence microscopy image sequences of live cells requires full automation of all processing steps involved: cell segmentation and tracking followed by foci segmentation and pattern analysis. Integrated systems for this purpose are lacking.nnnRESULTSnExtending our previous work in cell segmentation and tracking, we developed a new system for performing fully automated analysis of fluorescent foci in single cells. The system was validated by applying it to two common tasks: intracellular foci counting (in DNA damage repair experiments) and cell-phase identification based on foci pattern analysis (in DNA replication experiments). Experimental results show that the system performs comparably to expert human observers. Thus, it may replace tedious manual analyses for the considered tasks, and enables high-content screening.nnnAVAILABILITY AND IMPLEMENTATIONnThe described system was implemented in MATLAB (The MathWorks, Inc., USA) and compiled to run within the MATLAB environment. The routines together with four sample datasets are available at http://celmia.bigr.nl/. The software is planned for public release, free of charge for non-commercial use, after publication of this article.

Using GOMS and NASA-TLX to Evaluate Human-Computer Interaction Process in Interactive Segmentation

ABSTRACT HCI plays an important role in interactive medical image segmentation. The Goals, Operators, Methods, and Selection rules (GOMS) model and the National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire are different methods that are often used to evaluate the HCI process. In this article, we aim at improving the HCI process of interactive segmentation using both the GOMS model and the NASA-TLX questionnaire to: 1) identify the relations between these two methods and 2) propose HCI design suggestions based on the synthesis of the evaluation results using both methods. For this, we conducted an experiment where three physicians used two interactive segmentation approaches to segment different types of organs at risk for radiotherapy planning. Using the GOMS model, we identified 16 operators and 10 methods. Further analysis discovered strong relations between the use of GOMS operators and the results of the NASA-TLX questionnaire. Finally, HCI design issues were identified, and suggestions were proposed based on the evaluation results and the identified relations.

Automated segmentation of atherosclerotic histology based on pattern classification

Background: Histology sections provide accurate information on atherosclerotic plaque composition, and are used in various applications. To our knowledge, no automated systems for plaque component segmentation in histology sections currently exist. Materials and Methods: We perform pixel-wise classification of fibrous, lipid, and necrotic tissue in Elastica Von Gieson-stained histology sections, using features based on color channel intensity and local image texture and structure. We compare an approach where we train on independent data to an approach where we train on one or two sections per specimen in order to segment the remaining sections. We evaluate the results on segmentation accuracy in histology, and we use the obtained histology segmentations to train plaque component classification methods in ex vivo Magnetic resonance imaging (MRI) and in vivo MRI and computed tomography (CT). Results: In leave-one-specimen-out experiments on 176 histology slices of 13 plaques, a pixel-wise accuracy of 75.7 ± 6.8% was obtained. This increased to 77.6 ± 6.5% when two manually annotated slices of the specimen to be segmented were used for training. Rank correlations of relative component volumes with manually annotated volumes were high in this situation (P = 0.82-0.98). Using the obtained histology segmentations to train plaque component classification methods in ex vivo MRI and in vivo MRI and CT resulted in similar image segmentations for training on the automated histology segmentations as for training on a fully manual ground truth. The size of the lipid-rich necrotic core was significantly smaller when training on fully automated histology segmentations than when manually annotated histology sections were used. This difference was reduced and not statistically significant when one or two slices per section were manually annotated for histology segmentation. Conclusions: Good histology segmentations can be obtained by automated segmentation, which show good correlations with ground truth volumes. In addition, these can be used to develop segmentation methods in other imaging modalities. Accuracy increases when one or two sections of the same specimen are used for training, which requires a limited amount of user interaction in practice.

White-matter microstructure and hearing acuity in older adults: a population-based cross-sectional DTI study

To study the relation between the microstructure of white matter in the brain and hearing function in older adults we carried out a population-based, cross-sectional study. In 2562 participants of the Rotterdam Study, we conducted diffusion tensor imaging to determine the microstructure of the white-matter tracts. We performed pure-tone audiogram and digit-in-noise tests to quantify hearing acuity. Poorer white-matter microstructure, especially in the association tracts, was related to poorer hearing acuity. After differentiating the separate white-matter tracts in the left and right hemisphere, poorer white-matter microstructure in the right superior longitudinal fasciculus and the right uncinate fasciculus remained significantly associated with worse hearing. These associations did not significantly differ between middle-aged (51-69xa0years old) and older (70-100xa0years old) participants. Progressing age was thus not found to be an effect modifier. In a voxel-based analysis no voxels in the white matter were significantly associated with hearing impairment.

3D Regression Neural Network for the Quantification of Enlarged Perivascular Spaces in Brain MRI

&NA; Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automated quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the experts visual score was 0.74. Our method outperforms by a large margin ‐ more than 0.10 ‐ four more conventional automated approaches based on intensities, scale‐invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper‐parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan‐rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automated EPVS scoring correlates similarly to age as visual scoring.

Fastr: A Workflow Engine for Advanced Data Flows in Medical Image Analysis

With the increasing number of datasets encountered in imaging studies, the increasing complexity of processing workflows, and a growing awareness for data stewardship, there is a need for managed, automated workflows. In this paper we introduce Fastr, an automated workflow engine with support for advanced data flows. Fastr has built-in data provenance for recording processing trails and ensuring reproducible results. The extensible plugin-based design allows the system to interface with virtually any image archive and processing infrastructure. This workflow engine is designed to consolidate quantitative imaging biomarker pipelines in order to enable easy application to new data.

XNAT imaging platform for BioMedBridges and CTMM TraIT

* Correspondence: s.klein@erasmusmc.nl Biomedical Imaging Group Rotterdam, Departments of Medical Informatics & Radiology, Erasmus MC, 3000CA Rotterdam, the Netherlands Full list of author information is available at the end of the article Figure 1 XNAT user interface. Example project with magnetic resonance imaging (MRI) data of the brain. Klein et al. Journal of Clinical Bioinformatics 2015, 5(Suppl 1):S18 http://www.jclinbioinformatics.com/content/5/S1/S18 JOURNAL OF CLINICAL BIOINFORMATICS

Towards Robust CT-Ultrasound Registration Using Deep Learning Methods

Multi-modal registration, especially CT/MR to ultrasound (US), is still a challenge, as conventional similarity metrics such as mutual information do not match the imaging characteristics of ultrasound. The main motivation for this work is to investigate whether a deep learning network can be used to directly estimate the displacement between a pair of multi-modal image patches, without explicitly performing similarity metric and optimizer, the two main components in a registration framework. The proposed DVNet is a fully convolutional neural network and is trained using a large set of artificially generated displacement vectors (DVs). The DVNet was evaluated on mono- and simulated multi-modal data, as well as real CT and US liver slices (selected from 3D volumes). The results show that the DVNet is quite robust on the single- and multi-modal (simulated) data, but does not work yet on the real CT and US images.

Automatic normative quantification of brain tissue volume to support the diagnosis of dementia: A clinical evaluation of diagnostic accuracy

Objectives To assesses whether automated brain image analysis with quantification of structural brain changes improves diagnostic accuracy in a memory clinic setting. Methods In 42 memory clinic patients, we evaluated whether automated quantification of brain tissue volumes, hippocampal volume and white matter lesion volume improves diagnostic accuracy for Alzheimers disease (AD) and frontotemporal dementia (FTD), compared to visual interpretation. Reference data were derived from a dementia-free aging population (nu202f=u202f4915, aged >45u202fyears), and were expressed as age- and sex-specific percentiles. Experienced radiologists determined the most likely imaging-based diagnosis based on structural brain MRI using three strategies (visual assessment of MRI only, quantitative normative information only, or a combination of both). Diagnostic accuracy of each strategy was calculated with the clinical diagnosis as the reference standard. Results Providing radiologists with only quantitative data decreased diagnostic accuracy both for AD and FTD compared to conventional visual rating. The combination of quantitative with visual information, however, led to better diagnostic accuracy compared to only visual ratings for AD. This was not the case for FTD. Conclusion Quantitative assessment of structural brain MRI combined with a reference standard in addition to standard visual assessment may improve diagnostic accuracy in a memory clinic setting.

Enlarged perivascular spaces in brain MRI: Automated quantification in four regions

&NA; Enlarged perivascular spaces (PVS) are structural brain changes visible in MRI, are common in aging, and are considered a reflection of cerebral small vessel disease. As such, assessing the burden of PVS has promise as a brain imaging marker. Visual and manual scoring of PVS is a tedious and observer‐dependent task. Automated methods would advance research into the etiology of PVS, could aid to assess what a “normal” burden is in aging, and could evaluate the potential of PVS as a biomarker of cerebral small vessel disease. In this work, we propose and evaluate an automated method to quantify PVS in the midbrain, hippocampi, basal ganglia and centrum semiovale. We also compare associations between (earlier established) determinants of PVS and visual PVS scores versus the automated PVS scores, to verify whether automated PVS scores could replace visual scoring of PVS in epidemiological and clinical studies. Our approach is a deep learning algorithm based on convolutional neural network regression, and is contingent on successful brain structure segmentation. In our work we used FreeSurfer segmentations. We trained and validated our method on T2‐contrast MR images acquired from 2115 subjects participating in a population‐based study. These scans were visually scored by an expert rater, who counted the number of PVS in each brain region. Agreement between visual and automated scores was found to be excellent for all four regions, with intraclass correlation coefficients (ICCs) between 0.75 and 0.88. These values were higher than the inter‐observer agreement of visual scoring (ICCs between 0.62 and 0.80). Scan‐rescan reproducibility was high (ICCs between 0.82 and 0.93). The association between 20 determinants of PVS, including aging, and the automated scores were similar to those between the same 20 determinants of PVS and visual scores. We conclude that this method may replace visual scoring and facilitate large epidemiological and clinical studies of PVS.