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Alzheimers Disease Neuroimaging Initiative (1U01AG024904-01)
75 Research products (1 rule applied)
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  • 2014-2023
  • Open Access
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    Authors: Zuo, Qiankun; Chen, Ling; Wang, Shuqiang;

    Effective connectivity estimation plays a crucial role in understanding the interactions and information flow between different brain regions. However, the functional time series used for estimating effective connentivity is derived from certain software, which may lead to large computing errors because of different parameter settings and degrade the ability to model complex causal relationships between brain regions. In this paper, a brain diffuser with hierarchical transformer (BDHT) is proposed to estimate effective connectivity for mild cognitive impairment (MCI) analysis. To our best knowledge, the proposed brain diffuer is the first generative model to apply diffusion models in the application of generating and analyzing multimodal brain networks. Specifically, the BDHT leverages the structural connectivity to guide the reverse processes in an efficient way. It makes the denoising process more reliable and guarantees effective connectivity estimation accuracy. To improve denoising quality, the hierarchical denoising transformer is designed to learn multi-scale features in topological space. Furthermore, the GraphConFormer block can concentrate on both global and adjacent connectivity information. By stacking the multi-head attention and graph convolutional network, the proposed model enhances structure-function complementarity and improves the ability in noise estimation. Experimental evaluations of the denoising diffusion model demonstrate its effectiveness in estimating effective connectivity. The method achieves superior performance in terms of accuracy and robustness compared to existing approaches. It can captures both unidirectal and bidirectional interactions between brain regions, providing a comprehensive understanding of the brain's information processing mechanisms. Comment: 12pages, 14 figures

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    Authors: Lee, Brian N.; Wang, Junwen; Nho, Kwangsik; Saykin, Andrew J.; +1 Authors

    Alzheimer's Disease (AD) is a highly heritable neurodegenerative disorder characterized by memory impairments. Understanding how genetic factors contribute to AD pathology may inform interventions to slow or prevent the progression of AD. We performed stratified genetic analyses of 1,574 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to examine associations between levels of quantitative traits (QT's) and future diagnosis. The Chow test was employed to determine if an individual's genetic profile affects identified predictive relationships between QT's and future diagnosis. Our chow test analysis discovered that cognitive and PET-based biomarkers differentially predicted future diagnosis when stratifying on allelic dosage of AD loci. Post-hoc bootstrapped and association analyses of biomarkers confirmed differential effects, emphasizing the necessity of stratified models to realize individualized AD diagnosis prediction. This novel application of the Chow test allows for the quantification and direct comparison of genetic-based differences. Our findings, as well as the identified QT-future diagnosis relationships, warrant future investigation from a biological context.

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    Authors: Wang, Xinkai; Feng, Yanbo; Tong, Boning; Bao, Jingxuan; +5 Authors

    STREAMLINE is a simple, transparent, end-to-end automated machine learning (AutoML) pipeline for easily conducting rigorous machine learning (ML) modeling and analysis. The initial version is limited to binary classification. In this work, we extend STREAMLINE through implementing multiple regression-based ML models, including linear regression, elastic net, group lasso, and L21 norm. We demonstrate the effectiveness of the regression version of STREAMLINE by applying it to the prediction of Alzheimer's disease (AD) cognitive outcomes using multimodal brain imaging data. Our empirical results demonstrate the feasibility and effectiveness of the newly expanded STREAMLINE as an AutoML pipeline for evaluating AD regression models, and for discovering multimodal imaging biomarkers.

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    Authors: Tong, Boning; Risacher, Shannon L.; Bao, Jingxuan; Feng, Yanbo; +6 Authors

    Amyloid imaging has been widely used in Alzheimer's disease (AD) diagnosis and biomarker discovery through detecting the regional amyloid plaque density. It is essential to be normalized by a reference region to reduce noise and artifacts. To explore an optimal normalization strategy, we employ an automated machine learning (AutoML) pipeline, STREAMLINE, to conduct the AD diagnosis binary classification and perform permutation-based feature importance analysis with thirteen machine learning models. In this work, we perform a comparative study to evaluate the prediction performance and biomarker discovery capability of three amyloid imaging measures, including one original measure and two normalized measures using two reference regions (i.e., the whole cerebellum and the composite reference region). Our AutoML results indicate that the composite reference region normalization dataset yields a higher balanced accuracy, and identifies more AD-related regions based on the fractioned feature importance ranking.

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    Authors: Eitel, Fabian;

    Deep learning and especially convolutional neural networks (CNNs) have a high potential of being implemented into clinical decision support software for tasks such as diagnosis and prediction of disease courses. This thesis has studied the application of CNNs on structural MRI data for diagnosing neurological diseases. Specifically, multiple sclerosis and Alzheimer’s disease were used as classification targets due to their high prevalence, data availability and apparent biomarkers in structural MRI data. The classification task is challenging since pathology can be highly individual and difficult for human experts to detect and due to small sample sizes, which are caused by the high acquisition cost and sensitivity of medical imaging data. A roadblock in adopting CNNs to clinical practice is their lack of interpretability. Therefore, after optimizing the machine learning models for predictive performance (e.g. balanced accuracy), we have employed explainability methods to study the reliability and validity of the trained models. The deep learning models achieved good predictive performance of over 87% balanced accuracy on all tasks and the explainability heatmaps showed coherence with known clinical biomarkers for both disorders. Explainability methods were compared quantitatively using brain atlases and shortcomings regarding their robustness were revealed. Further investigations showed clear benefits of transfer-learning and image registration on the model performance. Lastly, a new CNN layer type was introduced, which incorporates a prior on the spatial homogeneity of neuro-MRI data. CNNs excel when used on natural images which possess spatial heterogeneity, and even though MRI data and natural images share computational similarities, the composition and orientation of neuro-MRI is very distinct. The introduced patch-individual filter (PIF) layer breaks the assumption of spatial invariance of CNNs and reduces convergence time on different data sets without reducing predictive performance. The presented work highlights many challenges that CNNs for disease diagnosis face on MRI data and defines as well as tests strategies to overcome those. In dieser Doktorarbeit wird die Frage untersucht, wie erfolgreich deep learning bei der Diagnostik von neurodegenerativen Erkrankungen unterstützen kann. In 5 experimentellen Studien wird die Anwendung von Convolutional Neural Networks (CNNs) auf Daten der Magnetresonanztomographie (MRT) untersucht. Ein Schwerpunkt wird dabei auf die Erklärbarkeit der eigentlich intransparenten Modelle gelegt. Mit Hilfe von Methoden der erklärbaren künstlichen Intelligenz (KI) werden Heatmaps erstellt, die die Relevanz einzelner Bildbereiche für das Modell darstellen. Die 5 Studien dieser Dissertation zeigen das Potenzial von CNNs zur Krankheitserkennung auf neurologischen MRT, insbesondere bei der Kombination mit Methoden der erklärbaren KI. Mehrere Herausforderungen wurden in den Studien aufgezeigt und Lösungsansätze in den Experimenten evaluiert. Über alle Studien hinweg haben CNNs gute Klassifikationsgenauigkeiten erzielt und konnten durch den Vergleich von Heatmaps zur klinischen Literatur validiert werden. Weiterhin wurde eine neue CNN Architektur entwickelt, spezialisiert auf die räumlichen Eigenschaften von Gehirn MRT Bildern.

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    Authors: Bouayed, Aymene Mohammed; Deslauriers-Gauthier, Samuel; Zucchelli, Mauro; Deriche, Rachid;

    Recently, a general analytical formula to extract all the Rotation Invariant Features (RIFs) of the diffusion Magnetic Resonance Imaging (dMRI) signal was proposed. The features extracted using this formula represent a generalisation of the usual second degree RIFs such as the mean diffusivity. In this work, we study the usefulness of all the 12 algebraically independent RIFs extracted from 4th degree spherical harmonics that model the dMRI signal per voxel in the context of Alzheimer Disease (AD) identification. To do so, and since we are working with imbalanced data sets, we first introduce a non-linear metric to evaluate the performance of the models, the (B-score). This proposed metric allows high score only when both classes are distinguished correctly. We use the proposed metric in conjunction with a deep Convolutional Neural Network that operates on subject slices to identify if a subject has AD or not. We find that micro-structure information communicated by RIFs is indeed useful to AD identification and that not all RIFs are equivalently useful. We also identify the two best RIF combinations for the ADNI-SIEMENS and the ADNI-GE medical data sets respectively. The combination of these RIFs achieves a classification B-score of 73.62% and 72.31% on the previous data sets respectively. We note the importance of combining high degree RIFs with low degree ones to improve the classification performance. International audience

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    Authors: Khorramyar, Pooriya;

    A Neurodegenerative Disease (ND) is progressive damage to brain neurons, which the human body cannot repair or replace. The well-known examples of such conditions are Dementia and Alzheimer’s Disease (AD), which affect millions of lives each year. Although conducting numerous researches, there are no effective treatments for the mentioned diseases today. However, early diagnosis is crucial in disease management. Diagnosing NDs is challenging for neurologists and requires years of training and experience. So, there has been a trend to harness the power of deep learning, including state-of-the-art Convolutional Neural Network (CNN), to assist doctors in diagnosing such conditions using brain scans. The CNN models lead to promising results comparable to experienced neurologists in their diagnosis. But, the advent of transformers in the Natural Language Processing (NLP) domain and their outstanding performance persuaded Computer Vision (CV) researchers to adapt them to solve various CV tasks in multiple areas, including the medical field. This research aims to develop Vision Transformer (ViT) models using Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset to classify NDs. More specifically, the models can classify three categories (Cognitively Normal (CN), Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD)) using brain Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) scans. Also, we take advantage of Automated Anatomical Labeling (AAL) brain atlas and attention maps to develop explainable models. We propose three ViTs, the best of which obtains an accuracy of 82% on the test dataset with the help of transfer learning. Also, we encode the AAL brain atlas information into the best performing ViT, so the model outputs the predicted label, the most critical region in its prediction, and overlaid attention map on the input scan with the crucial areas highlighted. Furthermore, we develop two CNN models with 2D and 3D convolutional kernels as baselines to classify NDs, which achieve accuracy of 77% and 73%, respectively, on the test dataset. We also conduct a study to find out the importance of brain regions and their combinations in classifying NDs using ViTs and the AAL brain atlas. This thesis was awarded a prize of 50,000 SEK by Getinge Sterilization for projects within Health Innovation.

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    Authors: Sakr, Fatemah;

    In dieser Dissertation wurden neue Biomarker untersucht, die die diagnostische Genauigkeit verbessern und das Fortschreiten der Alzheimer-Krankheit in den frühen Phasen vorhersagen könnten. Es wird erwartet, dass sie Risiko basierte Stratifizierung von Personen ermöglichen, die mit ihrer spezifischen Krankheitslast verbunden sind, d.h. kortikale Amyloidose und Lipidstörungen. Beide Ansätze ermöglichten eine präzisere Charakterisierung der Probanden, was für die Planung klinischer Studien und die Annahme neuer Maßnahmen in Präventionsstudien entscheidend sein könnte. This doctoral dissertation explored novel biomarkers that could reinforce diagnostic accuracy and predict disease progression in the early phases of AD. Such biomarkers are expected to allow the stratification of individuals based on the risk associated with their specific pathology burden, i.e., region-specific cortical amyloidosis and lipids dysregulations. Both approaches enabled higher precision in research participants' characterization, which could be crucial in planning clinical trials and adopting new interventions in prevention trials.

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    https://doi.org/10.18453/rosdo...
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      https://doi.org/10.18453/rosdo...
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    Convolutional neural networks have enabled significant improvements in medical image-based diagnosis. It is, however, increasingly clear that these models are susceptible to performance degradation when facing spurious correlations and dataset shift, leading, e.g., to underperformance on underrepresented patient groups. In this paper, we compare two classification schemes on the ADNI MRI dataset: a simple logistic regression model using manually selected volumetric features, and a convolutional neural network trained on 3D MRI data. We assess the robustness of the trained models in the face of varying dataset splits, training set sex composition, and stage of disease. In contrast to earlier work in other imaging modalities, we do not observe a clear pattern of improved model performance for the majority group in the training dataset. Instead, while logistic regression is fully robust to dataset composition, we find that CNN performance is generally improved for both male and female subjects when including more female subjects in the training dataset. We hypothesize that this might be due to inherent differences in the pathology of the two sexes. Moreover, in our analysis, the logistic regression model outperforms the 3D CNN, emphasizing the utility of manual feature specification based on prior knowledge, and the need for more robust automatic feature selection.

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    Authors: Lila, Eardi; Zhang, Wenbo; Rane, Swati;

    We introduce a novel framework for the classification of functional data supported on non-linear, and possibly random, manifold domains. The motivating application is the identification of subjects with Alzheimer's disease from their cortical surface geometry and associated cortical thickness map. The proposed model is based upon a reformulation of the classification problem into a regularized multivariate functional linear regression model. This allows us to adopt a direct approach to the estimation of the most discriminant direction while controlling for its complexity with appropriate differential regularization. Our approach does not require prior estimation of the covariance structure of the functional predictors, which is computationally not feasible in our application setting. We provide a theoretical analysis of the out-of-sample prediction error of the proposed model and explore the finite sample performance in a simulation setting. We apply the proposed method to a pooled dataset from the Alzheimer's Disease Neuroimaging Initiative and the Parkinson's Progression Markers Initiative, and are able to estimate discriminant directions that capture both cortical geometric and thickness predictive features of Alzheimer's Disease, which are consistent with the existing neuroscience literature.

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Alzheimers Disease Neuroimaging Initiative (1U01AG024904-01)
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Zuo, Qiankun; Chen, Ling; Wang, Shuqiang;

    Effective connectivity estimation plays a crucial role in understanding the interactions and information flow between different brain regions. However, the functional time series used for estimating effective connentivity is derived from certain software, which may lead to large computing errors because of different parameter settings and degrade the ability to model complex causal relationships between brain regions. In this paper, a brain diffuser with hierarchical transformer (BDHT) is proposed to estimate effective connectivity for mild cognitive impairment (MCI) analysis. To our best knowledge, the proposed brain diffuer is the first generative model to apply diffusion models in the application of generating and analyzing multimodal brain networks. Specifically, the BDHT leverages the structural connectivity to guide the reverse processes in an efficient way. It makes the denoising process more reliable and guarantees effective connectivity estimation accuracy. To improve denoising quality, the hierarchical denoising transformer is designed to learn multi-scale features in topological space. Furthermore, the GraphConFormer block can concentrate on both global and adjacent connectivity information. By stacking the multi-head attention and graph convolutional network, the proposed model enhances structure-function complementarity and improves the ability in noise estimation. Experimental evaluations of the denoising diffusion model demonstrate its effectiveness in estimating effective connectivity. The method achieves superior performance in terms of accuracy and robustness compared to existing approaches. It can captures both unidirectal and bidirectional interactions between brain regions, providing a comprehensive understanding of the brain's information processing mechanisms. Comment: 12pages, 14 figures

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    Europe PubMed Central
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    Authors: Lee, Brian N.; Wang, Junwen; Nho, Kwangsik; Saykin, Andrew J.; +1 Authors

    Alzheimer's Disease (AD) is a highly heritable neurodegenerative disorder characterized by memory impairments. Understanding how genetic factors contribute to AD pathology may inform interventions to slow or prevent the progression of AD. We performed stratified genetic analyses of 1,574 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to examine associations between levels of quantitative traits (QT's) and future diagnosis. The Chow test was employed to determine if an individual's genetic profile affects identified predictive relationships between QT's and future diagnosis. Our chow test analysis discovered that cognitive and PET-based biomarkers differentially predicted future diagnosis when stratifying on allelic dosage of AD loci. Post-hoc bootstrapped and association analyses of biomarkers confirmed differential effects, emphasizing the necessity of stratified models to realize individualized AD diagnosis prediction. This novel application of the Chow test allows for the quantification and direct comparison of genetic-based differences. Our findings, as well as the identified QT-future diagnosis relationships, warrant future investigation from a biological context.

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    Authors: Wang, Xinkai; Feng, Yanbo; Tong, Boning; Bao, Jingxuan; +5 Authors

    STREAMLINE is a simple, transparent, end-to-end automated machine learning (AutoML) pipeline for easily conducting rigorous machine learning (ML) modeling and analysis. The initial version is limited to binary classification. In this work, we extend STREAMLINE through implementing multiple regression-based ML models, including linear regression, elastic net, group lasso, and L21 norm. We demonstrate the effectiveness of the regression version of STREAMLINE by applying it to the prediction of Alzheimer's disease (AD) cognitive outcomes using multimodal brain imaging data. Our empirical results demonstrate the feasibility and effectiveness of the newly expanded STREAMLINE as an AutoML pipeline for evaluating AD regression models, and for discovering multimodal imaging biomarkers.

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    Authors: Tong, Boning; Risacher, Shannon L.; Bao, Jingxuan; Feng, Yanbo; +6 Authors

    Amyloid imaging has been widely used in Alzheimer's disease (AD) diagnosis and biomarker discovery through detecting the regional amyloid plaque density. It is essential to be normalized by a reference region to reduce noise and artifacts. To explore an optimal normalization strategy, we employ an automated machine learning (AutoML) pipeline, STREAMLINE, to conduct the AD diagnosis binary classification and perform permutation-based feature importance analysis with thirteen machine learning models. In this work, we perform a comparative study to evaluate the prediction performance and biomarker discovery capability of three amyloid imaging measures, including one original measure and two normalized measures using two reference regions (i.e., the whole cerebellum and the composite reference region). Our AutoML results indicate that the composite reference region normalization dataset yields a higher balanced accuracy, and identifies more AD-related regions based on the fractioned feature importance ranking.

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    Authors: Eitel, Fabian;

    Deep learning and especially convolutional neural networks (CNNs) have a high potential of being implemented into clinical decision support software for tasks such as diagnosis and prediction of disease courses. This thesis has studied the application of CNNs on structural MRI data for diagnosing neurological diseases. Specifically, multiple sclerosis and Alzheimer’s disease were used as classification targets due to their high prevalence, data availability and apparent biomarkers in structural MRI data. The classification task is challenging since pathology can be highly individual and difficult for human experts to detect and due to small sample sizes, which are caused by the high acquisition cost and sensitivity of medical imaging data. A roadblock in adopting CNNs to clinical practice is their lack of interpretability. Therefore, after optimizing the machine learning models for predictive performance (e.g. balanced accuracy), we have employed explainability methods to study the reliability and validity of the trained models. The deep learning models achieved good predictive performance of over 87% balanced accuracy on all tasks and the explainability heatmaps showed coherence with known clinical biomarkers for both disorders. Explainability methods were compared quantitatively using brain atlases and shortcomings regarding their robustness were revealed. Further investigations showed clear benefits of transfer-learning and image registration on the model performance. Lastly, a new CNN layer type was introduced, which incorporates a prior on the spatial homogeneity of neuro-MRI data. CNNs excel when used on natural images which possess spatial heterogeneity, and even though MRI data and natural images share computational similarities, the composition and orientation of neuro-MRI is very distinct. The introduced patch-individual filter (PIF) layer breaks the assumption of spatial invariance of CNNs and reduces convergence time on different data sets without reducing predictive performance. The presented work highlights many challenges that CNNs for disease diagnosis face on MRI data and defines as well as tests strategies to overcome those. In dieser Doktorarbeit wird die Frage untersucht, wie erfolgreich deep learning bei der Diagnostik von neurodegenerativen Erkrankungen unterstützen kann. In 5 experimentellen Studien wird die Anwendung von Convolutional Neural Networks (CNNs) auf Daten der Magnetresonanztomographie (MRT) untersucht. Ein Schwerpunkt wird dabei auf die Erklärbarkeit der eigentlich intransparenten Modelle gelegt. Mit Hilfe von Methoden der erklärbaren künstlichen Intelligenz (KI) werden Heatmaps erstellt, die die Relevanz einzelner Bildbereiche für das Modell darstellen. Die 5 Studien dieser Dissertation zeigen das Potenzial von CNNs zur Krankheitserkennung auf neurologischen MRT, insbesondere bei der Kombination mit Methoden der erklärbaren KI. Mehrere Herausforderungen wurden in den Studien aufgezeigt und Lösungsansätze in den Experimenten evaluiert. Über alle Studien hinweg haben CNNs gute Klassifikationsgenauigkeiten erzielt und konnten durch den Vergleich von Heatmaps zur klinischen Literatur validiert werden. Weiterhin wurde eine neue CNN Architektur entwickelt, spezialisiert auf die räumlichen Eigenschaften von Gehirn MRT Bildern.

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    Authors: Bouayed, Aymene Mohammed; Deslauriers-Gauthier, Samuel; Zucchelli, Mauro; Deriche, Rachid;

    Recently, a general analytical formula to extract all the Rotation Invariant Features (RIFs) of the diffusion Magnetic Resonance Imaging (dMRI) signal was proposed. The features extracted using this formula represent a generalisation of the usual second degree RIFs such as the mean diffusivity. In this work, we study the usefulness of all the 12 algebraically independent RIFs extracted from 4th degree spherical harmonics that model the dMRI signal per voxel in the context of Alzheimer Disease (AD) identification. To do so, and since we are working with imbalanced data sets, we first introduce a non-linear metric to evaluate the performance of the models, the (B-score). This proposed metric allows high score only when both classes are distinguished correctly. We use the proposed metric in conjunction with a deep Convolutional Neural Network that operates on subject slices to identify if a subject has AD or not. We find that micro-structure information communicated by RIFs is indeed useful to AD identification and that not all RIFs are equivalently useful. We also identify the two best RIF combinations for the ADNI-SIEMENS and the ADNI-GE medical data sets respectively. The combination of these RIFs achieves a classification B-score of 73.62% and 72.31% on the previous data sets respectively. We note the importance of combining high degree RIFs with low degree ones to improve the classification performance. International audience

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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/