Arrow Research search

Author name cluster

Wiro J. Niessen

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

21 papers
1 author row

Possible papers

21

YNIMG Journal 2021 Journal Article

Analyzing the effect of APOE on Alzheimer’s disease progression using an event-based model for stratified populations

  • Vikram Venkatraghavan
  • Stefan Klein
  • Lana Fani
  • Leontine S. Ham
  • Henri Vrooman
  • M. Kamran Ikram
  • Wiro J. Niessen
  • Esther E. Bron

Alzheimer's disease (AD) is the most common form of dementia and is phenotypically heterogeneous. APOE is a triallelic gene which correlates with phenotypic heterogeneity in AD. In this work, we determined the effect of APOE alleles on the disease progression timeline of AD using a discriminative event-based model (DEBM). Since DEBM is a data-driven model, stratification into smaller disease subgroups would lead to more inaccurate models as compared to fitting the model on the entire dataset. Hence our secondary aim is to propose and evaluate novel approaches in which we split the different steps of DEBM into group-aspecific and group-specific parts, where the entire dataset is used to train the group-aspecific parts and only the data from a specific group is used to train the group-specific parts of the DEBM. We performed simulation experiments to benchmark the accuracy of the proposed approaches and to select the optimal approach. Subsequently, the chosen approach was applied to the baseline data of 417 cognitively normal, 235 mild cognitively impaired who convert to AD within 3 years, and 342 AD patients from the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset to gain new insights into the effect of APOE carriership on the disease progression timeline of AD. In the ε4 carrier group, the model predicted with high confidence that CSF Amyloidβ42 and the cognitive score of Alzheimer's Disease Assessment Scale (ADAS) are early biomarkers. Hippocampus was the earliest volumetric biomarker to become abnormal, closely followed by the CSF Phosphorylated Tau181 (PTAU) biomarker. In the homozygous ε3 carrier group, the model predicted a similar ordering among CSF biomarkers. However, the volume of the fusiform gyrus was identified as one of the earliest volumetric biomarker. While the findings in the ε4 carrier and the homozygous ε3 carrier groups fit the current understanding of progression of AD, the finding in the ε2 carrier group did not. The model predicted, with relatively low confidence, CSF Neurogranin as one of the earliest biomarkers along with cognitive score of Mini-Mental State Examination (MMSE). Amyloid β42 was found to become abnormal after PTAU. The presented models could aid understanding of the disease, and in selecting homogeneous group of presymptomatic subjects at-risk of developing symptoms for clinical trials.

Details DOI

YNICL Journal 2021 Journal Article

Cross-cohort generalizability of deep and conventional machine learning for MRI-based diagnosis and prediction of Alzheimer’s disease

  • Esther E. Bron
  • Stefan Klein
  • Janne M. Papma
  • Lize C. Jiskoot
  • Vikram Venkatraghavan
  • Jara Linders
  • Pauline Aalten
  • Peter Paul De Deyn

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI; 334 AD, 520 CN). Trained classifiers were subsequently applied to predict conversion to AD in ADNI MCI patients (231 converters, 628 non-converters) and in the independent Health-RI Parelsnoer Neurodegenerative Diseases Biobank data set. From this multi-center study representing a tertiary memory clinic population, we included 199 AD patients, 139 participants with subjective cognitive decline, 48 MCI patients converting to dementia, and 91 MCI patients who did not convert to dementia. AD-CN classification based on modulated GM maps resulted in a similar area-under-the-curve (AUC) for SVM (0.940; 95%CI: 0.924–0.955) and CNN (0.933; 95%CI: 0.918–0.948). Application to conversion prediction in MCI yielded significantly higher performance for SVM (AUC = 0.756; 95%CI: 0.720-0.788) than for CNN (AUC = 0.742; 95%CI: 0.709-0.776) (p<0.01 for McNemar's test). In external validation, performance was slightly decreased. For AD-CN, it again gave similar AUCs for SVM (0.896; 95%CI: 0.855–0.932) and CNN (0.876; 95%CI: 0.836–0.913). For prediction in MCI, performances decreased for both SVM (AUC = 0.665; 95%CI: 0.576-0.760) and CNN (AUC = 0.702; 95%CI: 0.624-0.786). Both with SVM and CNN, classification based on modulated GM maps significantly outperformed classification based on minimally processed images (p=0.01). Deep and conventional classifiers performed equally well for AD classification and their performance decreased only slightly when applied to the external cohort. We expect that this work on external validation contributes towards translation of machine learning to clinical practice.

Details DOI

YNIMG Journal 2021 Journal Article

Longitudinal diffusion MRI analysis using Segis-Net: A single-step deep-learning framework for simultaneous segmentation and registration

  • Bo Li
  • Wiro J. Niessen
  • Stefan Klein
  • Marius de Groot
  • M. Arfan Ikram
  • Meike W. Vernooij
  • Esther E. Bron

This work presents a single-step deep-learning framework for longitudinal image analysis, coined Segis-Net. To optimally exploit information available in longitudinal data, this method concurrently learns a multi-class segmentation and nonlinear registration. Segmentation and registration are modeled using a convolutional neural network and optimized simultaneously for their mutual benefit. An objective function that optimizes spatial correspondence for the segmented structures across time-points is proposed. We applied Segis-Net to the analysis of white matter tracts from N=8045 longitudinal brain MRI datasets of 3249 elderly individuals. Segis-Net approach showed a significant increase in registration accuracy, spatio-temporal segmentation consistency, and reproducibility compared with two multistage pipelines. This also led to a significant reduction in the sample-size that would be required to achieve the same statistical power in analyzing tract-specific measures. Thus, we expect that Segis-Net can serve as a new reliable tool to support longitudinal imaging studies to investigate macro- and microstructural brain changes over time.

Details DOI

YNIMG Journal 2021 Journal Article

Progression along data-driven disease timelines is predictive of Alzheimer’s disease in a population-based cohort

  • Vikram Venkatraghavan
  • Elisabeth J. Vinke
  • Esther E. Bron
  • Wiro J. Niessen
  • M. Arfan Ikram
  • Stefan Klein
  • Meike W. Vernooij

Data-driven disease progression models have provided important insight into the timeline of brain changes in AD phenotypes. However, their utility in predicting the progression of pre-symptomatic AD in a population-based setting has not yet been investigated. In this study, we investigated if the disease timelines constructed in a case-controlled setting, with subjects stratified according to APOE status, are generalizable to a population-based cohort, and if progression along these disease timelines is predictive of AD. Seven volumetric biomarkers derived from structural MRI were considered. We estimated APOE-specific disease timelines of changes in these biomarkers using a recently proposed method called co-initialized discriminative event-based modeling (co-init DEBM). This method can also estimate a disease stage for new subjects by calculating their position along the disease timelines. The model was trained and cross-validated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and tested on the population-based Rotterdam Study (RS) cohort. We compared the diagnostic and prognostic value of the disease stage in the two cohorts. Furthermore, we investigated if the rate of change of disease stage in RS participants with longitudinal MRI data was predictive of AD. In ADNI, the estimated disease timeslines for ϵ4 non-carriers and carriers were found to be significantly different from one another (p<0.001). The estimate disease stage along the respective timelines distinguished AD subjects from controls with an AUC of 0.83 in both APOEϵ4 non-carriers and carriers. In the RS cohort, we obtained an AUC of 0.83 and 0.85 in ϵ4 non-carriers and carriers, respectively. Progression along the disease timelines as estimated by the rate of change of disease stage showed a significant difference (p<0.005) for subjects with pre-symptomatic AD as compared to the general aging population in RS. It distinguished pre-symptomatic AD subjects with an AUC of 0.81 in APOEϵ4 non-carriers and 0.88 in carriers, which was better than any individual volumetric biomarker, or its rate of change, could achieve. Our results suggest that co-init DEBM trained on case-controlled data is generalizable to a population-based cohort setting and that progression along the disease timelines is predictive of the development of AD in the general population. We expect that this approach can help to identify at-risk individuals from the general population for targeted clinical trials as well as to provide biomarker based objective assessment in such trials.

Details DOI

YNIMG Journal 2020 Journal Article

Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study

  • Yaron Caspi
  • Rachel M. Brouwer
  • Hugo G. Schnack
  • Marieke E. van de Nieuwenhuijzen
  • Wiepke Cahn
  • René S. Kahn
  • Wiro J. Niessen
  • Aad van der Lugt

Normal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups. The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved. Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N = 482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line, and applying a global linear mixed model fitting. We report statistically significant increase in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decrease in the ICV afterward (-0.09%/y, or about -1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect. In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinalmeasure are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.

Details DOI

YNIMG Journal 2020 Journal Article

Neuro4Neuro: A neural network approach for neural tract segmentation using large-scale population-based diffusion imaging

  • Bo Li
  • Marius de Groot
  • Rebecca M.E. Steketee
  • Rozanna Meijboom
  • Marion Smits
  • Meike W. Vernooij
  • M. Arfan Ikram
  • Jiren Liu

Subtle changes in white matter (WM) microstructure have been associated with normal aging and neurodegeneration. To study these associations in more detail, it is highly important that the WM tracts can be accurately and reproducibly characterized from brain diffusion MRI. In addition, to enable analysis of WM tracts in large datasets and in clinical practice it is essential to have methodology that is fast and easy to apply. This work therefore presents a new approach for WM tract segmentation: Neuro4Neuro, that is capable of direct extraction of WM tracts from diffusion tensor images using convolutional neural network (CNN). This 3D end-to-end method is trained to segment 25 WM tracts in aging individuals from a large population-based study (N ​= ​9752, 1. 5T MRI). The proposed method showed good segmentation performance and high reproducibility, i. e. , a high spatial agreement (Cohen’s kappa, κ = 0. 72 − 0. 83 ) and a low scan-rescan error in tract-specific diffusion measures (e. g. , fractional anisotropy: ε = 1 % − 5 % ). The reproducibility of the proposed method was higher than that of a tractography-based segmentation algorithm, while being orders of magnitude faster (0. 5s to segment one tract). In addition, we showed that the method successfully generalizes to diffusion scans from an external dementia dataset (N ​= ​58, 3T MRI). In two proof-of-principle experiments, we associated WM microstructure obtained using the proposed method with age in a normal elderly population, and with disease subtypes in a dementia cohort. In concordance with the literature, results showed a widespread reduction of microstructural organization with aging and substantial group-wise microstructure differences between dementia subtypes. In conclusion, we presented a highly reproducible and fast method for WM tract segmentation that has the potential of being used in large-scale studies and clinical practice.

Details DOI

JBHI Journal 2020 Journal Article

Spatially Regularized Shape Analysis of the Hippocampus Using $P$-Spline Based Shape Regression

  • Hakim Christiaan Achterberg
  • Johan J. de Rooi
  • Meike W. Vernooij
  • M. Arfan Ikram
  • Wiro J. Niessen
  • Paul H. C. Eilers
  • Marleen de Bruijne

Shape analysis is increasingly becoming important to study changes in brain structures in relation to clinical neurological outcomes. This is a challenging task due to the high dimensionality of shape representations and the often limited number of available shapes. Current techniques counter the poor ratio between dimensions and sample size by using regularization in shape space, but do not take into account the spatial relations within the shapes. This can lead to models that are biologically implausible and difficult to interpret. We propose to use P-spline based regression, which combines a generalized linear model (GLM) with the coefficients described as B-splines and a penalty term that constrains the regression coefficients to be spatially smooth. Owing to the GLM, this method can naturally predict both continuous and discrete outcomes and can include non-spatial covariates without penalization. We evaluated our method on hippocampus shapes extracted from magnetic resonance (MR) images of 510 non-demented, elderly people. We related the hippocampal shape to age, memory score, and sex. The proposed method retained the good performance of current techniques, such as ridge regression, but produced smoother coefficient fields that are easier to interpret.

Details DOI

YNIMG Journal 2019 Journal Article

Disease progression timeline estimation for Alzheimer's disease using discriminative event based modeling

  • Vikram Venkatraghavan
  • Esther E. Bron
  • Wiro J. Niessen
  • Stefan Klein

Alzheimer's Disease (AD) is characterized by a cascade of biomarkers becoming abnormal, the pathophysiology of which is very complex and largely unknown. Event-based modeling (EBM) is a data-driven technique to estimate the sequence in which biomarkers for a disease become abnormal based on cross-sectional data. It can help in understanding the dynamics of disease progression and facilitate early diagnosis and prognosis by staging patients. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate than existing state-of-the-art EBM methods. The method first estimates for each subject an approximate ordering of events. Subsequently, the central ordering over all subjects is estimated by fitting a generalized Mallows model to these approximate subject-specific orderings based on a novel probabilistic Kendall's Tau distance. We also introduce the concept of relative distance between events which helps in creating a disease progression timeline. Subsequently, we propose a method to stage subjects by placing them on the estimated disease progression timeline. We evaluated the proposed method on Alzheimer's Disease Neuroimaging Initiative (ADNI) data and compared the results with existing state-of-the-art EBM methods. We also performed extensive experiments on synthetic data simulating the progression of Alzheimer's disease. The event orderings obtained on ADNI data seem plausible and are in agreement with the current understanding of progression of AD. The proposed patient staging algorithm performed consistently better than that of state-of-the-art EBM methods. Event orderings obtained in simulation experiments were more accurate than those of other EBM methods and the estimated disease progression timeline was observed to correlate with the timeline of actual disease progression. The results of these experiments are encouraging and suggest that discriminative EBM is a promising approach to disease progression modeling.

Details DOI

JBHI Journal 2019 Journal Article

Groupwise Multichannel Image Registration

  • Jean-Marie Guyader
  • Wyke Huizinga
  • Valerio Fortunati
  • Dirk H. J. Poot
  • Jifke F. Veenland
  • Margarethus M. Paulides
  • Wiro J. Niessen
  • Stefan Klein

Multichannel image registration is an important challenge in medical image analysis. Multichannel images result from modalities such as dual-energy CT or multispectral microscopy. Besides, multichannel feature images can be derived from acquired images, for instance, by applying multiscale feature banks to the original images to register. Multichannel registration techniques have been proposed, but most of them are applicable to only two multichannel images at a time. In the present study, we propose to formulate multichannel registration as a groupwise image registration problem. In this way, we derive a method that allows the registration of two or more multichannel images in a fully symmetric manner (i. e. , all images play the same role in the registration procedure), and therefore, has transitive consistency by definition. The method that we introduce is applicable to any number of multichannel images, any number of channels per image, and it allows to take into account correlation between any pair of images and not just corresponding channels. In addition, it is fully modular in terms of dissimilarity measure, transformation model, regularisation method, and optimisation strategy. For two multimodal datasets, we computed feature images from the initially acquired images, and applied the proposed registration technique to the newly created sets of multichannel images. MIND descriptors were used as feature images, and we chose total correlation as groupwise dissimilarity measure. Results show that groupwise multichannel image registration is a competitive alternative to the pairwise multichannel scheme, in terms of registration accuracy and insensitivity towards registration reference spaces.

Details DOI

YNIMG Journal 2019 Journal Article

Patterns of functional connectivity in an aging population: The Rotterdam Study

  • Hazel I. Zonneveld
  • Raimon HR. Pruim
  • Daniel Bos
  • Henri A. Vrooman
  • Ryan L. Muetzel
  • Albert Hofman
  • Serge ARB. Rombouts
  • Aad van der Lugt

Structural brain markers are studied extensively in the field of neurodegeneration, but are thought to occur rather late in the process. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain structure and function are also affected by ‘normal’ brain ageing. More information is needed on how functional connectivity relates to aging, particularly in the absence of overt neurodegenerative disease. We investigated the association of age with resting-state functional connectivity in 2878 non-demented persons between 50 and 95 years of age (54. 1% women) from the population-based Rotterdam Study. We obtained nine well-known resting state networks using data-driven methodology. Within the anterior default mode network, ventral attention network, and sensorimotor network, functional connectivity was significantly lower with older age. In contrast, functional connectivity was higher with older age within the visual network. Between resting state networks, we found patterns of both increases and decreases in connectivity in approximate equal proportions. Our results reinforce the notion that the aging brain undergoes a reorganization process, and serves as a solid basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease.

Details DOI

YNICL Journal 2018 Journal Article

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

  • Meike W. Vernooij
  • Bas Jasperse
  • Rebecca Steketee
  • Marcel Koek
  • Henri Vrooman
  • M. Arfan Ikram
  • Janne Papma
  • Aad van der Lugt

Objectives: To assesses whether automated brain image analysis with quantification of structural brain changes improves diagnostic accuracy in a memory clinic setting. Methods: = 4915, aged >45 years), 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.

Details DOI

YNIMG Journal 2018 Journal Article

Disconnection due to white matter hyperintensities is associated with lower cognitive scores

  • Carolyn D. Langen
  • Lotte G.M. Cremers
  • Marius de Groot
  • Tonya White
  • M. Arfan Ikram
  • Wiro J. Niessen
  • Meike W. Vernooij

Previous studies have linked global burden of age-related white matter hyperintensities (WMHs) to cognitive impairment. We aimed to determine how WMHs in individual white matter connections relate to measures of cognitive function relative to measures of connectivity which do not take WMHs into account. Brain connectivity and WMH-related disconnectivity were derived from 3714 participants of the population-based Rotterdam Study. Connectivity was represented by the structural connectome, which was defined using diffusion tensor data, whereas the disconnectome represented disconnectivity due to WMH. The relationship between (dis)connectivity and cognitive measures was estimated using linear regression. We found that lower disconnectivity and higher connectivity corresponded to better cognitive function. There were many more significant associations with cognitive function in the disconnectome than in the connectome. Most connectome associations attenuated when disconnection was included in the model. WMH-related disconnectivity was especially related to worse executive functioning. Better cognitive speed corresponded to higher connectivity in specific connections independent of WMH presence. We conclude that WMH-related disconnectivity explains more variation in cognitive function than does connectivity. Efficient wiring in specific connections is important to information processing speed independent of WMH presence.

Details DOI

JBHI Journal 2015 Journal Article

Feature Selection Based on the SVM Weight Vector for Classification of Dementia

  • Esther E. Bron
  • Marion Smits
  • Wiro J. Niessen
  • Stefan Klein

Computer-aided diagnosis of dementia using a support vector machine (SVM) can be improved with feature selection. The relevance of individual features can be quantified from the SVM weights as a significance map (p-map). Although these p-maps previously showed clusters of relevant voxels in dementia-related brain regions, they have not yet been used for feature selection. Therefore, we introduce two novel feature selection methods based on p-maps using a direct approach (filter) and an iterative approach (wrapper). To evaluate these p-map feature selection methods, we compared them with methods based on the SVM weight vector directly, t-statistics, and expert knowledge. We used MRI data from the Alzheimer's disease neuroimaging initiative classifying Alzheimer's disease (AD) patients, mild cognitive impairment (MCI) patients who converted to AD (MCIc), MCI patients who did not convert to AD (MCInc), and cognitively normal controls (CN). Features for each voxel were derived from gray matter morphometry. Feature selection based on the SVM weights gave better results than t-statistics and expert knowledge. The p-map methods performed slightly better than those using the weight vector. The wrapper method scored better than the filter method. Recursive feature elimination based on the p-map improved most for AD-CN: the area under the receiver-operating-characteristic curve (AUC) significantly increased from 90. 3% without feature selection to 92. 0% when selecting 1. 5%–3% of the features. This feature selection method also improved the other classifications: AD-MCI 0. 1% improvement in AUC (not significant), MCI-CN 0. 7%, and MCIc-MCInc 0. 1% (not significant). Although the performance improvement due to feature selection was limited, the methods based on the p-map generally had the best performance, and were therefore better in estimating the relevance of individual features.

Details DOI

YNIMG Journal 2015 Journal Article

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

  • Esther E. Bron
  • Marion Smits
  • Wiesje M. van der Flier
  • Hugo Vrenken
  • Frederik Barkhof
  • Philip Scheltens
  • Janne M. Papma
  • Rebecca M.E. Steketee

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n=30) and optionally on data from other sources (e. g. , the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63. 0% and an area under the receiver-operating-characteristic curve (AUC) of 78. 8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http: //caddementia. grand-challenge. org.

Details DOI

YNIMG Journal 2013 Journal Article

Improving alignment in Tract-based spatial statistics: Evaluation and optimization of image registration

  • Marius de Groot
  • Meike W. Vernooij
  • Stefan Klein
  • M. Arfan Ikram
  • Frans M. Vos
  • Stephen M. Smith
  • Wiro J. Niessen
  • Jesper L.R. Andersson

Anatomical alignment in neuroimaging studies is of such importance that considerable effort is put into improving the registration used to establish spatial correspondence. Tract-based spatial statistics (TBSS) is a popular method for comparing diffusion characteristics across subjects. TBSS establishes spatial correspondence using a combination of nonlinear registration and a “skeleton projection” that may break topological consistency of the transformed brain images. We therefore investigated feasibility of replacing the two-stage registration-projection procedure in TBSS with a single, regularized, high-dimensional registration. To optimize registration parameters and to evaluate registration performance in diffusion MRI, we designed an evaluation framework that uses native space probabilistic tractography for 23 white matter tracts, and quantifies tract similarity across subjects in standard space. We optimized parameters for two registration algorithms on two diffusion datasets of different quality. We investigated reproducibility of the evaluation framework, and of the optimized registration algorithms. Next, we compared registration performance of the regularized registration methods and TBSS. Finally, feasibility and effect of incorporating the improved registration in TBSS were evaluated in an example study. The evaluation framework was highly reproducible for both algorithms (R2 0. 993; 0. 931). The optimal registration parameters depended on the quality of the dataset in a graded and predictable manner. At optimal parameters, both algorithms outperformed the registration of TBSS, showing feasibility of adopting such approaches in TBSS. This was further confirmed in the example experiment.

Details DOI

YNIMG Journal 2012 Journal Article

Automated measurement of local white matter lesion volume

  • Fedde van der Lijn
  • Benjamin F.J. Verhaaren
  • M. Arfan Ikram
  • Stefan Klein
  • Marleen de Bruijne
  • Henri A. Vrooman
  • Meike W. Vernooij
  • Alexander Hammers

It has been hypothesized that white matter lesions at different locations may have different etiology and clinical consequences. Several approaches for the quantification of local white matter lesion load have been proposed in the literature, most of which rely on a distinction between lesions in a periventricular region close to the ventricles and a subcortical zone further away. In this work we present a novel automated method for local white matter lesion volume quantification in magnetic resonance images. The method segments and measures the white matter lesion volume in 43 regions defined by orientation and distance to the ventricles, which allows a more spatially detailed study of lesion load. The potential of the method was demonstrated by analyzing the effect of blood pressure on the regional white matter lesion volume in 490 elderly subjects taken from a longitudinal population study. The method was also compared to two commonly used techniques to assess the periventricular and subcortical lesion load. The main finding was that high blood pressure was primarily associated with lesion load in the vascular watershed area that forms the border between the periventricular and subcortical regions. It explains the associations found for both the periventricular and subcortical load computed for the same data, and that were reported in the literature. But the proposed method can localize the region of association with greater precision than techniques that distinguish between periventricular and subcortical lesions only.

Details DOI

YNIMG Journal 2011 Journal Article

Statistical analysis of minimum cost path based structural brain connectivity

  • Renske de Boer
  • Michiel Schaap
  • Fedde van der Lijn
  • Henri A. Vrooman
  • Marius de Groot
  • Aad van der Lugt
  • M. Arfan Ikram
  • Meike W. Vernooij

Diffusion MRI can be used to study the structural connectivity within the brain. Brain connectivity is often represented by a binary network whose topology can be studied using graph theory. We present a framework for the construction of weighted structural brain networks, containing information about connectivity, which can be effectively analyzed using statistical methods. Network nodes are defined by segmentation of subcortical structures and by cortical parcellation. Connectivity is established using a minimum cost path (mcp) method with an anisotropic local cost function based directly on diffusion weighted images. We refer to this framework as Statistical Analysis of Minimum cost path based Structural Connectivity (SAMSCo) and the weighted structural connectivity networks as mcp-networks. In a proof of principle study we investigated the information contained in mcp-networks by predicting subject age based on the mcp-networks of a group of 974 middle-aged and elderly subjects. Using SAMSCo, age was predicted with an average error of 3. 7years. This was significantly better than predictions based on fractional anisotropy or mean diffusivity averaged over the whole white matter or over the corpus callosum, which showed average prediction errors of at least 4. 8years. Additionally, we classified subjects, based on the mcp-networks, into groups with low and high white matter lesion load, while correcting for age, sex and white matter atrophy. The SAMSCo classification outperformed the classification based on the diffusion measures with a classification accuracy of 76. 0% versus 63. 2%. We also performed a classification in groups with mild and severe atrophy, correcting for age, sex and white matter lesion load. In this case, mcp-networks and diffusion measures yielded similar classification accuracies of 68. 3% and 67. 8% respectively. The SAMSCo prediction and classification experiments indicate that the mcp-networks contain information regarding age, white matter lesion load and white matter atrophy, and that in case of age and white matter lesion load the mcp-network based models outperformed the predictions based on diffusion measures.

Details DOI

YNIMG Journal 2010 Journal Article

Accuracy and reproducibility study of automatic MRI brain tissue segmentation methods

  • Renske de Boer
  • Henri A. Vrooman
  • M. Arfan Ikram
  • Meike W. Vernooij
  • Monique M.B. Breteler
  • Aad van der Lugt
  • Wiro J. Niessen

The ability to study changes in brain morphometry in longitudinal studies majorly depends on the accuracy and reproducibility of the brain tissue quantification. We evaluate the accuracy and reproducibility of four previously proposed automatic brain tissue segmentation methods: FAST, SPM5, an automatically trained k-nearest neighbor (kNN) classifier, and a conventional kNN classifier based on a prior training set. The intensity nonuniformity correction and skull-stripping mask were the same for all methods. Evaluations were performed on MRI scans of elderly subjects derived from the general population. Accuracy was evaluated by comparison to two manual segmentations of MRI scans of six subjects (mean age 65. 9±4. 4years). Reproducibility was assessed by comparing the automatic segmentations of 30 subjects (mean age 57. 0±3. 7years) who were scanned twice within a short time interval. All methods showed good accuracy and reproducibility, with only small differences between methods. The conventional kNN classifier was the most accurate method with similarity indices of 0. 82/0. 90/0. 94 for cerebrospinal fluid/gray matter/white matter, but it showed the lowest reproducibility. FAST yielded the most reproducible segmentation volumes with volume difference standard deviations of 0. 55/0. 49/0. 38 (percentage of intracranial volume) respectively. The results of the reproducibility experiment can be used to calculate the required number of subjects in the design of a longitudinal study with sufficient power to detect changes over time in brain (tissue) volume. Example sample size calculations demonstrate a rather large effect of the choice of segmentation method on the required number of subjects.

Details DOI

YNIMG Journal 2009 Journal Article

White matter lesion extension to automatic brain tissue segmentation on MRI

  • Renske de Boer
  • Henri A. Vrooman
  • Fedde van der Lijn
  • Meike W. Vernooij
  • M. Arfan Ikram
  • Aad van der Lugt
  • Monique M.B. Breteler
  • Wiro J. Niessen

A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

Details DOI

YNIMG Journal 2008 Journal Article

Hippocampus segmentation in MR images using atlas registration, voxel classification, and graph cuts

  • Fedde van der Lijn
  • Tom den Heijer
  • Monique M.B. Breteler
  • Wiro J. Niessen

Since hippocampal volume has been found to be an early biomarker for Alzheimer's disease, there is large interest in automated methods to accurately, robustly, and reproducibly extract the hippocampus from MRI data. In this work we present a segmentation method based on the minimization of an energy functional with intensity and prior terms, which are derived from manually labelled training images. The intensity energy is based on a statistical intensity model that is learned from the training images. The prior energy consists of a spatial and regularity term. The spatial prior is obtained from a probabilistic atlas created by registering the training images to the unlabelled target image, and deforming and averaging the training labels. The regularity prior energy encourages smooth segmentations. The resulting energy functional is globally minimized using graph cuts. The method was evaluated using image data from a population-based study on diseases among the elderly. Two set of images were used: a small set of 20 manually labelled MR images and a larger set of 498 images, for which manual volume measurements were available, but no segmentations. This data was previously used in a volumetry study that found significant associations between hippocampal volume and cognitive decline and incidence of dementia. Cross-validation experiments with the labelled set showed similarity indices of 0. 852 and 0. 864 and mean surface distances of 0. 40 and 0. 36 mm for the left and right hippocampus. 83% of the automated segmentations of the large set were rated as ‘good’ by a trained observer. Also, the proposed method was used to repeat the manual hippocampal volumetry study. The automatically obtained hippocampal volumes showed significant associations with cognitive decline and dementia, similar to the manually measured volumes. Finally, direct quantitative and qualitative comparisons showed that the proposed method outperforms a multi-atlas based segmentation method.

Details DOI

YNIMG Journal 2007 Journal Article

Multi-spectral brain tissue segmentation using automatically trained k-Nearest-Neighbor classification

  • Henri A. Vrooman
  • Chris A. Cocosco
  • Fedde van der Lijn
  • Rik Stokking
  • M. Arfan Ikram
  • Meike W. Vernooij
  • Monique M.B. Breteler
  • Wiro J. Niessen

Conventional k-Nearest-Neighbor (kNN) classification, which has been successfully applied to classify brain tissue in MR data, requires training on manually labeled subjects. This manual labeling is a laborious and time-consuming procedure. In this work, a new fully automated brain tissue classification procedure is presented, in which kNN training is automated. This is achieved by non-rigidly registering the MR data with a tissue probability atlas to automatically select training samples, followed by a post-processing step to keep the most reliable samples. The accuracy of the new method was compared to rigid registration-based training and to conventional kNN-based segmentation using training on manually labeled subjects for segmenting gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) in 12 data sets. Furthermore, for all classification methods, the performance was assessed when varying the free parameters. Finally, the robustness of the fully automated procedure was evaluated on 59 subjects. The automated training method using non-rigid registration with a tissue probability atlas was significantly more accurate than rigid registration. For both automated training using non-rigid registration and for the manually trained kNN classifier, the difference with the manual labeling by observers was not significantly larger than inter-observer variability for all tissue types. From the robustness study, it was clear that, given an appropriate brain atlas and optimal parameters, our new fully automated, non-rigid registration-based method gives accurate and robust segmentation results. A similarity index was used for comparison with manually trained kNN. The similarity indices were 0. 93, 0. 92 and 0. 92, for CSF, GM and WM, respectively. It can be concluded that our fully automated method using non-rigid registration may replace manual segmentation, and thus that automated brain tissue segmentation without laborious manual training is feasible.

Details DOI
v2026.09.13