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2. Fully Automated 3D Segmentation of MR-Imaged Calf Muscle Compartments: Neighborhood Relationship Enhanced Fully Convolutional Network

Author

Guo, Zhihui, Zhang, Honghai, Chen, Zhi, van der Plas, Ellen, Gutmann, Laurie, Thedens, Daniel, Nopoulos, Peggy, and Sonka, Milan

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Automated segmentation of individual calf muscle compartments from 3D magnetic resonance (MR) images is essential for developing quantitative biomarkers for muscular disease progression and its prediction. Achieving clinically acceptable results is a challenging task due to large variations in muscle shape and MR appearance. Although deep convolutional neural networks (DCNNs) achieved improved accuracy in various image segmentation tasks, certain problems such as utilizing long-range information and incorporating high-level constraints remain unsolved. We present a novel fully convolutional network (FCN), called FilterNet, that utilizes contextual information in a large neighborhood and embeds edge-aware constraints for individual calf muscle compartment segmentations. An encoder-decoder architecture with flexible backbone blocks is used to systematically enlarge convolution receptive field and preserve information at all resolutions. Edge positions derived from the FCN output muscle probability maps are explicitly regularized using kernel-based edge detection in an end-to-end optimization framework. Our FilterNet was evaluated on 40 T1-weighted MR images of 10 healthy and 30 diseased subjects by 4-fold cross-validation. Mean DICE coefficients of 88.00%--91.29% and mean absolute surface positioning errors of 1.04--1.66 mm were achieved for the five 3D muscle compartments., Comment: To be appeared in journal Computerized Medical Imaging and Graphics

Published
2020

15. Sex-Based Differences in Functional Brain Activity During Working Memory in Survivors of Pediatric Acute Lymphoblastic Leukemia

Author

Gandy, Kellen, primary, Scoggins, Matthew A, additional, Phillips, Nicholas, additional, van der Plas, Ellen, additional, Fellah, Slim, additional, Jacola, Lisa M, additional, Pui, Ching-Hon, additional, Hudson, Melissa M, additional, Reddick, Wilburn E, additional, Sitaram, Ranganatha, additional, and Krull, Kevin R, additional

Published
2022
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17. Characterizing academic performance in pediatric acute lymphoblastic leukemia with population‐based achievement tests

Author

Al‐Kaylani, Hend M., primary, Reasoner, Erin E., additional, Loeffler, Bradley T., additional, Mott, Sarah L., additional, Madasu, Susan, additional, Liu, Audrey, additional, Langbehn, Kathleen, additional, Conrad, Amy L., additional, Dickens, David, additional, Grafft, Amanda, additional, Harshman, Lyndsay, additional, Modi, Arunkumar J., additional, and van der Plas, Ellen, additional

Published
2021
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24. Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia

Author

van der Plas, Ellen, primary, Spencer Noakes, T. Leigh, additional, Butcher, Darci T., additional, Weksberg, Rosanna, additional, Galin-Corini, Laura, additional, Wanstall, Elizabeth A., additional, Te, Patrick, additional, Hopf, Laura, additional, Guger, Sharon, additional, Hitzler, Johann, additional, Schachar, Russell J., additional, Ito, Shinya, additional, and Nieman, Brian J., additional

Published
2020
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25. Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities

Author

Solomon, Matthew A., primary, van der Plas, Ellen, additional, Langbehn, Kathleen E., additional, Novak, Marci, additional, Schultz, Jordan L., additional, Koscik, Timothy R., additional, Conrad, Amy L., additional, Brophy, Patrick D., additional, Furth, Susan L., additional, Nopoulos, Peggy C., additional, and Harshman, Lyndsay A., additional

Published
2020
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26. Sex-Specific Associations Between Chemotherapy, Chronic Conditions, and Neurocognitive Impairment in Acute Lymphoblastic Leukemia Survivors: A Report From the Childhood Cancer Survivor Study

Author

van der Plas, Ellen, primary, Qiu, Weiyu, additional, Nieman, Brian J, additional, Yasui, Yutaka, additional, Liu, Qi, additional, Dixon, Stephanie B, additional, Kadan-Lottick, Nina S, additional, Weldon, Christopher B, additional, Weil, Brent R, additional, Jacola, Lisa M, additional, Gibson, Todd M, additional, Leisenring, Wendy, additional, Oeffinger, Kevin, additional, Hudson, Melissa M, additional, Robison, Leslie L, additional, Armstrong, Gregory T, additional, and Krull, Kevin R, additional

Published
2020
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28. Quantitative MRI outcomes in child and adolescent leukemia survivors: Evidence for global alterations in gray and white matter

Author

van der Plas, Ellen, primary, Spencer Noakes, T. Leigh, additional, Butcher, Darci T., additional, Weksberg, Rosanna, additional, Galin-Corini, Laura, additional, Wanstall, Elizabeth A., additional, Te, Patrick, additional, Hopf, Laura, additional, Guger, Sharon, additional, Spiegler, Brenda J., additional, Hitzler, Johann, additional, Schachar, Russell J., additional, Ito, Shinya, additional, and Nieman, Brian J., additional

Published
2020
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31. Brain Development and Heart Function after Systemic Single-Agent Chemotherapy in a Mouse Model of Childhood Leukemia Treatment

Author

Spencer Noakes, T. Leigh, primary, Przybycien, Thomas S., additional, Forwell, Amanda, additional, Nicholls, Connor, additional, Zhou, Yu-Qing, additional, Butcher, Darci T., additional, Weksberg, Rosanna, additional, Guger, Sharon L., additional, Spiegler, Brenda J., additional, Schachar, Russell J., additional, Hitzler, Johann, additional, Ito, Shinya, additional, van der Plas, Ellen, additional, and Nieman, Brian J., additional

Published
2018
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32. Sex-Specific Associations Between Chemotherapy, Chronic Conditions, and Neurocognitive Impairment in Acute Lymphoblastic Leukemia Survivors: A Report From the Childhood Cancer Survivor Study.

Author

van der Plas, Ellen, Qiu, Weiyu, Nieman, Brian J, Yasui, Yutaka, Liu, Qi, Dixon, Stephanie B, Kadan-Lottick, Nina S, Weldon, Christopher B, Weil, Brent R, Jacola, Lisa M, Gibson, Todd M, Leisenring, Wendy, Oeffinger, Kevin, Hudson, Melissa M, Robison, Leslie L, Armstrong, Gregory T, and Krull, Kevin R

Subjects
*LYMPHOBLASTIC leukemia, *ACUTE leukemia, *CHRONIC diseases, *CHILDHOOD cancer, *CANCER survivors, *RESEARCH, *CROSS-sectional method, *RESEARCH methodology, *EVALUATION research, *COMPARATIVE studies, *RESEARCH funding
Abstract

Background: The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only.Methods: This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided.Results: Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92).Conclusion: Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship. [ABSTRACT FROM AUTHOR]

Published
2021
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37. Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate.

Author

van der Plas, Ellen, Nieman, Brian J., Butcher, Darci T., Hitzler, Johann K., Weksberg, Rosanna, Ito, Shinya, and Schachar, Russell

Subjects
*CHEMOTHERAPY-related cognitive impairment, *LYMPHOBLASTIC leukemia, *METHOTREXATE, *MENTAL health of cancer patients, *OCCUPATIONAL achievement, *QUALITY of life, *PATHOLOGICAL psychology, *PATIENTS
Abstract

Childhood cancer survivors frequently experience long-lasting consequences of chemotherapy on health outcomes. Neurocognitive late effects of chemotherapy occur in 40 – 60% of acute lymphoblastic leukemia (ALL) survivors. These deficits affect mental health, school performance, job success, and are associated with poor quality of life, therefore presenting a clinical challenge for psychiatrists. However, not all cancer survivors are impacted by treatment in the same manner and emerging evidence suggests that genetic variation may modulate neurocognitive outcomes. Much like other complex psychopathologies, neurocognitive deficits in cancer survivors are the result of complex interactions between genetic and environmental variables. This review describes adverse neurocognitive outcomes observed in survivors of acute lymphoblastic leukemia (ALL) and discusses genetic variability in biochemical pathways targeted by chemotherapeutic agents as a possible mechanism contributing to psychopathology in ALL survivors. [ABSTRACT FROM AUTHOR]

Published
2015

39. GLI2 promoter hypermethylation in saliva of children with a respiratory allergy

Author

Greet Schoeters, Diether Lambrechts, Wim Vanden Berghe, Tijs Louwies, Katarzyna Szarc vel Szic, Guy Van Camp, Matthieu Moisse, Vera Nelen, Sofie De Prins, Sabine A. S. Langie, Patrick De Boever, Ellen van der Plas, Gudrun Koppen, LANGIE, Sabine, Moisse, Matthieu, Szic, Katarzyna Szarc Vel, Van der Plas, Ellen, Koppen, Gudrun, De Prins, Sofie, LOUWIES, Tijs, Nelen, Vera, Van Camp, Guy, Lambrechts, Diether, Schoeters, Greet, Vanden Berghe, Wim, and DE BOEVER, Patrick

Subjects
0301 basic medicine, Male, Saliva, lcsh:QH426-470, GLI2, lcsh:Medicine, Zinc Finger Protein Gli2/genetics, Epigenesis, Genetic, 03 medical and health sciences, DNA methylation, saliva, respiratory allergy, illumina methylation 450K beadChip, Belgium, Genetics, medicine, Humans, Epigenetics, Longitudinal Studies, Promoter Regions, Genetic, Child, Molecular Biology, Gene, Genetics (clinical), Lung, business.industry, Research, lcsh:R, Promoter, Saliva/chemistry, Methylation, Respiratory allergy, Human genetics, Illumina Methylation 450K BeadChip, Nuclear Proteins/genetics, lcsh:Genetics, 030104 developmental biology, medicine.anatomical_structure, Child, Preschool, Case-Control Studies, Immunology, CpG Islands, Female, Human medicine, business, Developmental Biology, Genome-Wide Association Study, Respiratory Hypersensitivity/genetics
Abstract

Background: The prevalence of respiratory allergy in children is increasing. Epigenetic DNA methylation changes are plausible underlying molecular mechanisms. Results: Saliva samples collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) were used to discover and confirm DNA methylation signatures that can differentiate individuals with respiratory allergy from healthy subjects. Genome-wide analysis with Illumina Methylation 450K BeadChips revealed 23 differentially methylated gene regions (DMRs) in saliva from 11y old allergic children (N=26) vs. controls (N=20) in FLEHS1. A subset of 7 DMRs was selected for confirmation by iPLEX MassArray analysis. First, iPLEX analysis was performed in the same 46 FLEHS1 samples for analytical confirmation of the findings obtained during the discovery phase. iPLEX results correlated significantly with the 450K array data (P < 0.0001) and confirmed 4 out of the 7 DMRs. Aiming for additional biological confirmation, the 7 DMRs were analyzed using iPLEX in a substudy of an independent birth cohort (FLEHS2; N=19 cases vs. 20 controls, aged 5 years). One DMR in the GLI2 promoter region showed a consistent statistically significant hypermethylation in individuals with respiratory allergy across the two birth cohorts and technologies. In addition to its involvement in TGF-beta signaling and T-helper differentiation, GLI2 has a regulating role in lung development. Conclusion: GLI2 is considered an interesting candidate DNA methylation marker for respiratory allergy. SL was the beneficiary of a post-doctoral grant from the AXA Research Fund and the Cefic-LRI Innovative Science Award 2013 and has currently a post-doctoral fellowship (12L5216N) provided by The Research Foundation-Flanders (FWO) and the Flemish Institute of Technological Research (VITO). The methylation work was funded by the Cefic-LRI Innovative Science Award 2013. PDB is recipient of a Bill & Melinda Gates Foundation Grand Challenges Exploration Grant (OPP119403) in the field of saliva biomarker discovery.

Published
2018

40. Characterization of brain development with neuroimaging in a female mouse model of chemotherapy treatment of acute lymphoblastic leukemia.

Author

Gandy K, Koscik TR, Alexander T, Steinberg JD, Krull KR, and van der Plas E

Abstract

Background: Survivors of pediatric acute lymphoblastic leukemia (ALL) exhibit abnormal neurocognitive outcomes that are possibly due to exposures to neurotoxic chemotherapy agents. This study aimed to determine the feasibility of characterizing long-term neuroanatomical changes with in vivo neuroimaging in a preclinical model of treatment for ALL., Methods: Female mice (C57BL/6) were randomly assigned to a saline control group (n=10) or a treatment group (n=10) that received intrathecal methotrexate and oral dexamethasone (IT-MTX + DEX). Mice were subsequently scanned three times on a 7T MRI at ages 3, 6, and 12 months (T1, T2, and T3, respectively), which corresponds with human age-equivalents spanning early to late adulthood. Regional brain volumes were automatically segmented, and volume change between timepoints (i.e., T1 to T2; and T2 to T3) were compared between groups (i.e., saline vs. IT-MTX + DEX)., Results: Five mice in the IT-MTX + DEX group, and seven mice in the saline group completed all three scans. Between T1 and T2, volumetric change was significantly different between groups in total gray matter [estimate =2.06, 95% confidence interval (CI): 0.27-3.84], the cerebrum (estimate =1.62, 95% CI: 0.14-3.09), claustrum (estimate =0.06, 95% CI: 0.02-0.09), amygdala (estimate =0.16, 95% CI: 0.03-0.29), and striatum (estimate =0.18, 95% CI: 0.01-0.35), with the IT-MTX + DEX group exhibiting a more robust increase in volume than the saline-treated group. Between T2 and T3, group differences in structural brain development were evident for total white matter (estimate =-0.14, 95% CI: -0.27 to -0.01), and the corpus callosum (estimate =-0.09, 95% CI: -0.19 to 0.00) and amygdala (estimate =-0.05, 95% CI: -0.10 to 0.00). In contrast to the rapid brain growth observed earlier in development (i.e., T1 to T2), the IT-MTX + DEX group exhibited an attenuated increase in volume relative to the saline-treated group between T2 and T3., Conclusions: The results demonstrate feasibility of modeling pediatric ALL treatment in a preclinical model and highlight the potential of using preclinical neuroimaging models to gain insight into brain development throughout survivorship., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-458/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Published
2024
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