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arXiv 2020年

作者： Chen, Antong Saouaf, Jennifer Zhou, Bo Crawford, Randolph Yuan, Jianda Ma, Junshui Baumgartner, Richard Wang, Shubing Goldmacher, Gregory Image Data Analytics Merck & Co. Inc. West PointPA United States School of Computer Science Carnegie Mellon University PittsburghPA United States Translational Oncology Merck & Co. Inc. RahwayNJ United States Biostatistics and Research Decision Science Merck & Co. Inc. RahwayNJ United States Translational Biomarkers Merck & Co. Inc. West PointPA United States

Herein we propose a deep learning-based approach for the prediction of lung lesion response based on radiomic features extracted from clinical CT scans of patients in non-small cell lung cancer trials. The approach starts with the classification of lung lesions from the set of primary and metastatic lesions at various anatomic locations. Focusing on the lung lesions, we perform automatic segmentation to extract their 3D volumes. Radiomic features are then extracted from the lesion on the pre-treatment scan and the first follow-up scan to predict which lesions will shrink at least 30% in diameter during treatment (either Pembrolizumab or combinations of chemotherapy and Pembrolizumab), which is defined as a partial response by the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. A 5-fold cross validation on the training set led to an AUC of 0.84 ± 0.03, and the prediction on the testing dataset reached AUC of 0.73 ± 0.02 for the outcome of 30% diameter shrinkage. Copyright © 2020, The Authors. All rights reserved.

关键词： Forecasting

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Cross-scale functional connectivity patterns of the aging brain learned from the multi-cohort iSTAGing study

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Alzheimer's & Dementia 2023年第S17期19卷

作者： Zhen Zhou Hongming Li Chau B Tran Yuncong Ma Dhivya Srinivasan Ahmed Abdulkadir Junhao Wen Guray Erus Elizabeth Mamourian Ilya M. Nasrallah Nick Bryan David A. Wolk Lori L Beason-Held Susan M. Resnick Haochang Shou Christos Davatzikos Yong Fan University of Pennsylvania philadelphia PA USA Perelman School of Medicine University of Pennsylvania Philadelphia PA USA University of Pennsylvania Philadelphia PA USA Center for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA Laboratory for Research in Neuroimaging Department of Clinical Neurosciences Lausanne University Hospital (CHUV) and University of Lausanne Lausanne Switzerland Centre for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Radiology University of Pennsylvania Philadelphia PA USA Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA University of Texas at Austin Austin TX USA Department of Pathology and Laboratory Medicine Alzheimer’s Disease Center Perelman School of Medicine University of Pennsylvania Philadelphia PA USA National Institute on Aging Baltimore MD USA Laboratory of Behavioral Neuroscience National Institute on Aging Baltimore MD USA Department of Biostatistics Epidemiology & Informatics University of Pennsylvania Philadelphia PA USA Correspondece

Background Brain functional connectivity (FC) measures derived from resting-state fMRI (rsfMRI) data have advanced our understanding of the brain organization. However, most existing studies investigate the brain functional networks (FNs) at a specific scale, ignoring potentially complementary FC information at different levels of spatial granularity as well as the cross-scale information. Given that the brain is a multi-scale, hierarchical system, FCs between FNs at different spatial scales may provide complementary information to those measured within-scales for characterizing the aging brain. Method We computed multiscale FNs to capture their FC measures across multiple scales and investigated the associations between cross-scale FCs and the brain aging based on rsfMRI data of a diverse cohort (n = 4186, aged 22 to 97 years) from seven sites of the iSTAGING study [1]. For each subject, we computed the FNs at seven scales, yielding seven sets of k (k = 17, 25, 50, 75, 100, 125 and 150) FNs, same as our previous study [2-3]. We estimated FC measures between the 542 FNs using Pearson’s correlation, yielding the cross-scale FC matrices that were harmonized across sites in the tangent space using ComBat-GAM [4] with sex and age as covariates. The harmonized FC measures were used as features to build an age prediction model using Ridge regression as illustrated in Figure 1. The brain age prediction model was compared with that built on harmonized FC measures between FNs of the same scales, with the performance estimated with a nested five-fold cross-validation. Result The cross-scale FC measures performed significantly better than the within-scale FC measures for the brain age prediction, as summarized in Table 1. Figure 2 shows the most informative FC measures for the brain age prediction. Specifically, FC measures computed both cross- and within-scales between the visual, somatomotor, and frontoparietal networks provided relatively more useful information for the bra

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Artificial intelligence reveals brain aging patterns in 27,402 individuals without diagnosed cognitive impairment that are linked to genetics, biomedical measures, and cognitive decline

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Alzheimer's & Dementia 2023年第S17期19卷

作者： Ioanna Skampardoni Ilya M. Nasrallah Junhao Wen Yuhan Cui Ahmed Abdulkadir Zhijian Yang Guray Erus Elizabeth Mamourian Ashish Singh Haochang Shou Li Shen Konstantina Nikita Christos Davatzikos iSTAGING consortium School of Electrical and Computer Engineering National Technical University of Athens Athens Greece Centre for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA Correspondece Department of Radiology University of Pennsylvania Philadelphia PA USA Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Laboratory for Research in Neuroimaging Department of Clinical Neurosciences Lausanne University Hospital (CHUV) and University of Lausanne Lausanne Switzerland 1Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Biostatistics Epidemiology & Informatics University of Pennsylvania Philadelphia PA USA University of Pennsylvania Philadelphia PA USA

Background Understanding heterogeneity of structural brain changes in aging may provide insights into susceptibility to neurodegenerative diseases. We characterize the genetics underlying brain structural heterogeneity within cognitively unimpaired (CU) individuals using data-driven machine learning applied to a diverse dataset of 27,402 individuals from 11 neuroimaging studies from the iSTAGING consortium. Method Structural brain morphologic patterns of CU individuals were independently examined in four decade-long intervals spanning ages 45 to 85. Within each interval, Smile-GAN (Yang et al., 2021) was trained on baseline anatomic and white matter hyperintensity (WMH) volumes. Smile-GAN probability scores were used as phenotypes in genome-wide association studies (GWAS). Specifically, we performed multiple linear regressions controlling for confounders (e.g., age) via Plink (Purcell et al., 2007). We observed longitudinal clustering stability across decades, so individuals from adjacent age groups were combined into broader age groups ([45,65), [65,85)) due to the large sample requirement of GWAS. Genomic loci, represented by the top leading single nucleotide polymorphisms (SNPs), were defined considering linkage disequilibrium. We investigated associations of SNPs with clinical traits and mapped them to genes using the GWAS Catalog (Buniello et al., 2019). Result Three structural brain aging patterns, relative to resilient agers (A0), consistent across decades, emerged: A1, or ‘typical’ aging with low atrophy and WMHs, and two ‘advanced’ aging patterns, one showing elevated WMHs and modest atrophy (A2) and the other displaying severe, widespread atrophy and moderate WMH load (A3) (Figure 1). GWAS discovered eight and six genomic loci in [45,65) and [65,85) age groups, respectively (Table 1, Figure 2). The lead SNPs for A1 and A2 were previously associated with several cardiometabolic risk factors, WMHs, and regional brain volumes. Interestingly, rs4843552, previo

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Development of a national pathology training system using digital pathology and SNOMED-CT

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Journal of Pathology Informatics 2025年

作者： Clare McGenity Alyn Cratchley Jocelyn Aldridge Craig Sayers W. Scott Campbell Rajesh C. Dash Adrienne M. Flanagan Neil Sebire Alexander Wright Waseem Akhtar Darren Treanor Leeds Teaching Hospitals NHS Trust Leeds UK Pathology and Data Analytics University of Leeds Leeds UK Department of Histopathology Mid Yorkshire NHS Foundation Trust Wakefield UK University of Nebraska Medical Center Department of Pathology Microbiology and Immunology Omaha NE USA Department of Pathology Duke University Health System Durham NC USA Department of Histopathology Royal National Orthopaedic Hospital Middlesex UK UCL Cancer Institute London UK Department of Histopathology National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Center and UCL London UK Department of Clinical Pathology and Department of Clinical and Experimental Medicine Linköping University Linköping Sweden Centre for Medical Image Science and Visualization (CMIV) Linköping University Linköping Sweden

Introduction Digital pathology is an important resource in modern pathology education, with many examples of large databases of educational cases now available online. However, there remains a lack of standardization in retrieval and categorization of cases for training within and between institutions. Methods Over 1600 teaching terms applicable to histopathology were developed and mapped to corresponding SNOMED CT terms to create a large directory of teaching cases. This was then integrated as a pre-defined list into a clinical PACS system for a national digital pathology project covering multiple hospitals and pathology training programs. Results This resource allows easy allocation of teaching term labels to cases with educational value. A substantial catalog of educational cases has been generated already, with ongoing efforts to expand this with cases from routine clinical practice. The catalog is fully searchable by term for use in training and examinations. Conclusions A large directory of digital pathology teaching cases was developed with associated corresponding SNOMED CT terms. The directory of terms will be shared with other healthcare providers to expand its use and utility.

关键词： Digital pathology Teaching Education Ontology SNOMED CT

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Dynamic radiomics: A new methodology to extract quantitative time-related features from tomographic images

arXiv

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arXiv 2020年

作者： Che, Fengying Shi, Ruichuan Li, Shuqin Wu, Jian Li, Haoran Chen, Weixing Zhang, Hao Qu, Hui Li, Zhi Cui, Xiaoyu College of Medicine and Biological Information Engineering Northeastern University Liaoning Shenyang China Key Laboratory of Intelligent Computing in Medical Image Ministry of Education Key Laboratory of Data Analytics and Optimization for Smart Industry Northeastern University Liaoning Shenyang China Department of Medical Oncology The First Affiliated Hospital of China Medical University Liaoning110001 China Shenzhen College of Advanced Technology University of the Chinese Academy of Sciences Beijing100049 China Department of Breast Surgery Liaoning Cancer Hospital and Institute Cancer Hospital of China Medical University Liaoning Shenyang110042 China

The feature extraction methods of radiomics are mainly based on static tomographic images at a certain moment, while the occurrence and development of disease is a dynamic process that cannot be fully reflected by only static characteristics. This study proposes a new dynamic radiomics feature extraction workflow that uses time-dependent tomographic images of the same patient, focuses on the changes in image features over time, and then quantifies them as new dynamic features for diagnostic or prognostic evaluation. We first define the mathematical paradigm of dynamic radiomics and introduce three specific methods that can describe the transformation process of features over time. Three different clinical problems are used to validate the performance of the proposed dynamic feature with conventional 2D and 3D static *** results show that compared with static features, dynamic feature extraction can achieve higher robustness and accuracy for time-dependent tomographic images. We also found that the dynamic features that influence different clinical problems are also quite different. Copyright © 2020, The Authors. All rights reserved.

关键词： Tomography

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Saliency Weighted Convolutional Features for Instance Search

Saliency Weighted Convolutional Features for Instance Search

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International Workshop on Content-Based Multimedia Indexing, CBMI

作者： Eva Mohedano Kevin McGuinness Xavier Giró-i-Nieto Noel E. O'Connor Insight Centre for Data Analytics Dublin City University Ireland Image Processing Group Universitat Politècnica de Catalunya Spain

ISBN: (纸本)9781538670224

This work explores attention models to weight the contribution of local convolutional representations for the instance search task. We present a retrieval framework based on bags of local convolutional features (BLCF) that benefits from saliency weighting to build an efficient image representation. The use of human visual attention models (saliency) allows significant improvements in retrieval performance without the need to conduct region analysis or spatial verification, and without requiring any feature fine tuning. We investigate the impact of different saliency models, finding that higher performance on saliency benchmarks does not necessarily equate to improved performance when used in instance search tasks. The proposed approach outperforms the state-of-the-art on the challenging INSTRE benchmark by a large margin, and provides similar performance on the Oxford and Paris benchmarks compared to more complex methods that use off-the-shelf representations. Source code is publicly available at https:***/imatge-upc/salbow.

关键词： Benchmark testing Visualization Task analysis Convolutional codes Vocabulary image representation Training

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Discovering Alzheimer’s disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering

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Alzheimer's & Dementia 2023年第S17期19卷

作者： Zhijian Yang Junhao Wen Ahmed Abdulkadir Yuhan Cui Guray Erus Elizabeth Mamourian Randa Melhem Dhivya Srinivasan Sindhuja Tirumalai Govindarajan Jiong Chen Mohamad Habes Colin L Masters Paul Maruff Jurgen Fripp Luigi Ferrucci Marilyn S. Albert Sterling C Johnson John C Morris Pamela LaMontagne Daniel S. Marcus Tammie L.S. Benzinger David A. Wolk Li Shen Jingxuan Bao Susan M. Resnick Duygu Tosun Haochang Shou Ilya M. Nasrallah Christos Davatzikos the Alzheimer’s Disease Neuroimaging Initiative, the Preclinical AD Consortium, the Baltimore Longitudinal Study of Aging, and the iSTAGING study 1Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Correspondece Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA University of Bern Bern Switzerland Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL) Center for and Data Science for Integrated Diagnostics (AI2D) Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Center for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA Centre for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia PA USA University of Texas Health San Antonio San Antonio TX USA Florey Institute of Neuroscience and Mental Health Parkville VIC Australia The Florey Institute of Neuroscience and Mental Health University of Melbourne Parkville VIC Australia CSIRO Health and Biosecurity Australian E-Health Research Centre Brisbane QLD Australia National Institute on Aging NIH Baltimore MD USA Department of Neurology Johns Hopkins University School of Medicine Baltimore MD USA Wisconsin Alzheimer’s Institute University of Wisconsin-Madison School of Medicine and Public Health Madison WI USA Knight Alzheimer Disease Research Center St. Louis MO USA Washington University School of Medicine Saint Louis MO USA Washington University School of Medicine St. Louis MO USA Department of Neurology University of Pennsylvania School of Medicine Philadelphia PA USA Institute for Biomedical Informatics University of Pennsylvania ATHENS PA USA University of Pennsylvania Philadelphia PA USA Laboratory of Behavioral Neuroscience National Institute on Aging Baltimore MD USA Department of Radiology and Biomedical Imaging University of Cal

Background The heterogeneity of neurodegenerative diseases, including Alzheimer’s disease (AD), has hampered precision diagnosis and treatment. Machine learning methods enable the identification of genetically-explained disease subtypes with distinct brain phenotypes. Method Gene-SGAN is a novel, multi-view, weakly-supervised deep clustering method that jointly considers phenotypic and genetic data, thereby deriving subtypes of disease-related brain changes with genetic associations. We apply the method to derive subtypes related to AD. Analyses used structural MRIs and whole-genome sequencing data from the Alzheimer’s Disease Neuroimaging Initiative (1,533 participants, including controls and patients with Mild Cognitive Impairment (MCI) and AD). Result Gene-SGAN identified four distinct subtypes within MCI/AD: A1, normal anatomy; A2, focal medial temporal lobe (MTL) atrophy; A3, severe atrophy in neocortex and MTL; A4, severe cortical but relatively modest MTL atrophy (Figure 1). The four subtypes reveal significant differences in seven known AD-related genetic variants (Figure 2). The identified subtype-associated SNPs not only resemble previous findings, but also suggest genetic protective effects contributing to the observed resilience (A1), potential inflammatory mechanisms underlying subtypes (A2&A3), and the effect of SNPs on atypical atrophy patterns of AD (A4). Clinically, A1 and A3 participants showed the best and the worst cognitive performances (Figure 3). A3 participants had the most abnormal CSF Aβ (p<0.001 vs. A1&A4 and p = 0.039 vs. A2), and exhibited the highest white matter hyperintensity (WMH) volumes (p<0.001 vs. A1&A4 and p = 0.017 vs. A2). However, A2 participants showed significantly higher CSF phospho-tau than A3 participants (p = 0.019). A4 participants were the youngest group (p<0.001 vs. all other groups), suggesting the inclusion of early onset AD participants, who have a higher prevalence of hippocampal-sparing variants such as posterio

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Why is the Winner the Best?

Why is the Winner the Best?

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Conference on Computer Vision and Pattern Recognition (CVPR)

作者： M. Eisenmann A. Reinke V. Weru M. D. Tizabi F. Isensee T. J. Adler S. Ali V. Andrearczyk M. Aubreville U. Baid S. Bakas N. Balu S. Bano J. Bernal S. Bodenstedt A. Casella V. Cheplygina M. Daum M. De Bruijne A. Depeursinge R. Dorent J. Egger D. G. Ellis S. Engelhardt M. Ganz N. Ghatwary G. Girard P. Godau A. Gupta L. Hansen K. Harada M. Heinrich N. Heller A. Hering A. Huaulmé P. Jannin A. E. Kavur O. Kodym M. Kozubek J. Li H. Li J. Ma C. Martín-Isla B. Menze A. Noble V. Oreiller N. Padoy S. Pati K. Payette T. Rädsch J. Rafael-Patiño V. Singh Bawa S. Speidel C. H. Sudre K. Van Wijnen M. Wagner D. Wei A. Yamlahi M. H. Yap C. Yuan M. Zenk A. Zia D. Zimmerer D. Aydogan B. Bhattarai L. Bloch R. Brüngel J. Cho C. Choi Q. Dou I. Ezhov C. M. Friedrich C. Fuller R. R. Gaire A. Galdran Á. García Faura M. Grammatikopoulou S. Hong M. Jahanifar I. Jang A. Kadkhodamohammadi I. Kang F. Kofler S. Kondo H. Kuijf M. Li M. Luu T. Martinčič P. Morais M. A. Naser B. Oliveira D. Owen S. Pang J. Park S. Park S. Płotka E. Puybareau N. Rajpoot K. Ryu N. Saeed A. Shephard P. Shi D. Štepec R. Subedi G. Tochon H. R. Torres H. Urien J. L. Vilaça K. A. Wahid H. Wang J. Wang L. Wang X. Wang B. Wiestler M. Wodzinski F. Xia J. Xie Z. Xiong S. Yang Y. Yang Z. Zhao K. Maier-Hein P. F. Jäger A. Kopp-Schneider L. Maier-Hein Division of Intelligent Medical Systems German Cancer Research Center (DKFZ) Heidelberg Germany Helmholtz Imaging German Cancer Research Center (DKFZ) Heidelberg Germany Faculty of Mathematics and Computer Science Heidelberg University Heidelberg Germany Division of Biostatistics German Cancer Research Center (DKFZ) Heidelberg Germany Division of Medical Image Computing German Cancer Research Center (DKFZ) Heidelberg Germany Faculty of Engineering and Physical Sciences School of Computing University of Leeds Leeds UK Institute of Informatics School of Management HES-SO Valais-Wallis University of Applied Sciences and Arts Western Switzerland Sierre Switzerland Department of Nuclear Medicine and Molecular Imaging Lausanne University Hospital Lausanne Switzerland Technische Hochschule Ingolstadt Ingolstadt Germany Center for Artificial Intelligence and Data Science for Integrated Diagnostics (AI2D) and Center for Biomedical Image Computing and Analytics (CBICA) University of Pennsylvania Philadelphia PA USA Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Radiology University of Washington Seattle WA USA Department of Computer Science Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) University College London London UK Universitat Autònoma de Barcelona & Computer Vision Center Barcelona Spain Division of Translational Surgical Oncology National Center for Tumor Diseases (NCT/UCC) Dresden Dresden Germany Department of Advanced Robotics Istituto Italiano di Tecnologia Italy Department of Electronics Information and Bioengineering Politecnico di Milano Milan Italy IT University of Copenhagen Copenhagen Denmark Department of General Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany Department of Radiology and Nuc

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multicenter study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and post-processing (66%). The “typical” lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

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Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease

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Computers in Biology and Medicine 2024年 176卷 108588-108588页

作者： Gómez-Pascual, Alicia Naccache, Talel Xu, Jin Hooshmand, Kourosh Wretlind, Asger Gabrielli, Martina Lombardo, Marta Tiffany Shi, Liu Buckley, Noel J. Tijms, Betty M. Vos, Stephanie J.B. ten Kate, Mara Engelborghs, Sebastiaan Sleegers, Kristel Frisoni, Giovanni B. Wallin, Anders Lleó, Alberto Popp, Julius Martinez-Lage, Pablo Streffer, Johannes Barkhof, Frederik Zetterberg, Henrik Visser, Pieter Jelle Lovestone, Simon Bertram, Lars Nevado-Holgado, Alejo J. Gualerzi, Alice Picciolini, Silvia Proitsi, Petroula Verderio, Claudia Botía, Juan A. Legido-Quigley, Cristina Department of Information and Communications Engineering Faculty of Informatics University of Murcia Murcia Spain Steno Diabetes Center Copenhagen Herlev Denmark Department of Data Science City University of London United Kingdom Institute of Pharmaceutical Science King's College London London United Kingdom CNR Institute of Neuroscience Vedano al Lambro20854 Italy School of Medicine and Surgery University of Milano-Bicocca 20126 Italy Oxford United Kingdom Department of Psychiatry University of Oxford United Kingdom Kavli Institute for Nanoscience Discovery Denmark Alzheimer Center VU University Medical Center Amsterdam Netherlands Department of Psychiatry and Neuropsychology Alzheimer Centrum Limburg Maastricht University Maastricht Netherlands Department of Biomedical Sciences University of Antwerp Antwerp Belgium Vrije Universiteit Brussel Brussels Belgium Complex Genetics Group VIB Center for Molecular Neurology VIB Antwerp Belgium Institute Born-Bunge Department of Biomedical Sciences University of Antwerp Antwerp Belgium University of Geneva Geneva Switzerland IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia Italy Institute of Neuroscience and Physiology Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden Barcelona Spain Old age psychiatry University Hospital of Lausanne University of Lausanne Switzerland Department of Geriatric Psychiatry University Hospital of Psychiatry Zürich University of Zürich Switzerland CITA-Alzheimer Foundation San Sebastian Spain AC Immune SA formerly Janssen R&D LLC. Beerse Belgium at the time of study conduct Lausanne Switzerland Department of Radiology and Nuclear Medicine Amsterdam UMC Vrije Universiteit Netherlands Queen Square Institute of Neurology and Centre for Medical Image Computing University College London United Kingdom Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden Department of Psychiatry and Neurochemistry Institute of

Background: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Method: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Results: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. Conclusions: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways. © 2024 The Authors

关键词： Metabolites

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LGG-52. Volumetry-based response characterization of recurrent pediatric low-grade gliomas in PNOC clinical Neuro-oncology trials

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Neuro-Oncology 2022年第SUPPLEMENT_1期24卷 i100–i100页

作者： Marc von Reppert MingDe Lin Khaled Bousabarah Ariana Familiar Ryan Velasco Angela Waanders Arastoo Vossough Amanda Haddock Theodore Nicolaides Kristin Swanson Anahita Kazerooni Cassie Kline Ali Nabavizadeh Daphne Haas-Kogan Michael Prados Joshua Rubin Sabine Mueller Mariam Aboian Department of Radiology &amp Biomedical Imaging Yale School of Medicine New Haven CT USA Visage Imaging Inc San Diego CA USA Visage Imaging GmbH Berlin Germany Center for Data Driven Discovery in Biomedicine Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago IL USA Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Children' s Brain Tumor Network Center for Biomedical Image Computing and Analytics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Division of Pediatric Hematology/Oncology NYU Langone Medical Center New York NY USA Mathematical NeuroOncology Lab Precision Neurotherapeutics Innovation Program Mayo Clinic Phoenix AZ USA Center for Biomedical Image Computing and Analytics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Division of Oncology Children’s Hospital of Philadelphia Philadelphia PA USA Department of Radiation Oncology Dana-Farber Cancer Institute Brigham and Women's Hospital Harvard Medical School Boston MA USA Division of Neuro-Oncology Department of Neurological Surgery University of California San Francisco CA USA Department of Pediatrics and Neuroscience Washington University School of Medicine St. Louis MO USA Departments of Pediatrics Neurology and Neurological Surgery University of California San Francisco San Francisco CA USA

BACKGROUND : Endpoints in clinical trials using novel treatments are evaluated by RANO criteria, which provide an estimate of tumor size from two-dimensional measurements along the most prominent axial slice. However, pediatric low-grade gliomas (pLGG) commonly have variegated shapes with solid and cystic components, potentially resulting in misevaluation of true tumor volume and thus, ultimately, trial outcome. OBJECTIVES : We aim to characterize treatment response through volumetric assessment of progressive/recurrent pLGGs treated with single-agent everolimus on PNOC001 clinical trial. We seek to identify clinically relevant criteria that provide added value to response assessment beyond 2D measurements. METHODS : In a cohort of 44 patients we performed 3D-segmentation of solid, cystic and whole tumor within our PACS-framework and compared results to previously carried-out central imaging review by RANO criteria which had yielded 15 PD, 27 SD, 2 PR and 0 CR. RESULTS : 8 tumors were solid only and 36 had a mixed solid-cystic appearance. When evaluating the entire tumor (i.e. solid and cystic components combined) and using the same RANO cutoff criteria, one case changed from PR to SD, one changed from SD to PR, 3 changed from SD to PD, and 7 changed from PD to SD, resulting in an overall discordance of 27% of cases. CONCLUSION : We propose that incorporation of volumetrics into response assessment provides additional and potentially more accurate information beyond RANO-based measurements. It is crucial to note that the above-reported changes represent numerical discrepancies as opposed to true-to-reality changes in clinical outcome. Determining representative thresholds for the deployment of volumetric measures in clinical trials will be critical. Future work will include data from the PNOC002 clinical trial and evaluate inter-reader agreement and reader discordance. With the availability of PACS-based 3D-tools in neuroradiology practice, well-defined volumetric c

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