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      Stroke atlas of the brain: Voxel-wise density-based clustering of infarct lesions topographic distribution

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          Abstract

          Objective

          The supply territories of main cerebral arteries are predominantly identified based on distribution of infarct lesions in patients with large arterial occlusion; whereas, there is no consensus atlas regarding the supply territories of smaller end-arteries. In this study, we applied a data-driven approach to construct a stroke atlas of the brain using hierarchical density clustering in large number of infarct lesions, assuming that voxels/regions supplied by a common end-artery tend to infarct together.

          Methods

          A total of 793 infarct lesions on MRI scans of 458 patients were segmented and coregistered to MNI-152 standard brain space. Applying a voxel-wise data-driven hierarchical density clustering algorithm, we identified those voxels that were most likely to be part of same infarct lesions in our dataset. A step-wise clustering scheme was applied, where the clustering threshold was gradually decreased to form the first 20 mother (>50 cm 3) or main (1–50 cm 3) clusters in addition to any possible number of tiny clusters (<1 cm 3); and then, any resultant mother clusters were iteratively subdivided using the same scheme. Also, in a randomly selected 2/3 subset of our cohort, a bootstrapping cluster analysis with 100 permutations was performed to assess the statistical robustness of proposed clusters.

          Results

          Approximately 91% of the MNI-152 brain mask was covered by 793 infarct lesions across patients. The covered area of brain was parcellated into 4 mother, 16 main, and 123 tiny clusters at the first hierarchy level. Upon iterative clustering subdivision of mother clusters, the brain tissue was eventually parcellated into 1 mother cluster (62.6 cm 3), 181 main clusters (total volume 1107.3 cm 3), and 917 tiny clusters (total volume of 264.8 cm 3). In bootstrap analysis, only 0.12% of voxels, were labelled as “unstable” – with a greater reachability distance in cluster scheme compared to their corresponding mean bootstrapped reachability distance. On visual assessment, the mother/main clusters were formed along supply territories of main cerebral arteries at initial hierarchical levels, and then tiny clusters emerged in deep white matter and gray matter nuclei prone to small vessel ischemic infarcts.

          Conclusions

          Applying voxel-wise data-driven hierarchical density clustering on a large number of infarct lesions, we have parcellated the brain tissue into clusters of voxels that tend to be part of same infarct lesion, and presumably representing end-arterial supply territories. This hierarchical stroke atlas of the brain is shared publicly, and can potentially be applied for future infarct location-outcome analysis.

          Highlights

          • Using data-driven density clustering, a hierarchical brain atlas is constructed to identify voxels likely to infarct together.

          • Different clusters can potentially be extracted from dendrogram through thresholding at different reachability thresholds.

          • The hierarchical stroke atlas hypothetically represents the detailed anatomical distribution of distal arties in the brain.

          • The stroke atlas is made publicly available for potential future location-outcome correlation studies in stroke patients.

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          Most cited references23

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          Stereotaxic display of brain lesions.

          Traditionally lesion location has been reported using standard templates, text based descriptions or representative raw slices from the patient's CT or MRI scan. Each of these methods has drawbacks for the display of neuroanatomical data. One solution is to display MRI scans in the same stereotaxic space popular with researchers working in functional neuroimaging. Presenting brains in this format is useful as the slices correspond to the standard anatomical atlases used by neuroimagers. In addition, lesion position and volume are directly comparable across patients. This article describes freely available software for presenting stereotaxically aligned patient scans. This article focuses on MRI scans, but many of these tools are also applicable to other modalities (e.g. CT, PET and SPECT). We suggest that this technique of presenting lesions in terms of images normalized to standard stereotaxic space should become the standard for neuropsychological studies.
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            Bootstrapping cluster analysis: assessing the reliability of conclusions from microarray experiments.

            We introduce a general technique for making statistical inference from clustering tools applied to gene expression microarray data. The approach utilizes an analysis of variance model to achieve normalization and estimate differential expression of genes across multiple conditions. Statistical inference is based on the application of a randomization technique, bootstrapping. Bootstrapping has previously been used to obtain confidence intervals for estimates of differential expression for individual genes. Here we apply bootstrapping to assess the stability of results from a cluster analysis. We illustrate the technique with a publicly available data set and draw conclusions about the reliability of clustering results in light of variation in the data. The bootstrapping procedure relies on experimental replication. We discuss the implications of replication and good design in microarray experiments.
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              A large, open source dataset of stroke anatomical brain images and manual lesion segmentations

              Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities. Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation. However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation. Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise. While algorithms have been developed to automate this process, the results often lack accuracy. Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance. Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata. This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods. We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                13 August 2019
                2019
                13 August 2019
                : 24
                : 101981
                Affiliations
                [a ]Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
                [b ]Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
                [c ]Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA
                [d ]Stevens Neuroimaging and Informatics Institute, Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
                [e ]Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, USA
                [f ]Department of Radiology, University of Minnesota, Minneapolis, MN, USA
                [g ]Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA
                Author notes
                [* ]Correspondence to: Y. Wang, Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden. yanlu.wang@ 123456ki.se
                [** ]Correspondence to: S. Payabvash, Department of Radiology and Biomedical, maging, Yale School of Medicine, Box 208042, Tompkins East 2, 333 Cedar St, New Haven, CT 06520-8042, USA. sam.payabvash@ 123456yale.edu
                [1]

                Drs. Wang and Payabvash contributed equally to this work.

                Article
                S2213-1582(19)30331-6 101981
                10.1016/j.nicl.2019.101981
                6728875
                31473544
                f638152f-003b-4f3c-9b46-70894b773706
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 April 2019
                : 19 July 2019
                : 11 August 2019
                Categories
                Regular Article

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