scholarly journals QOL-09. WHOLE-BRAIN WHITE MATTER NETWORK CONNECTIVITY IS DISRUPTED BY PEDIATRIC BRAIN TUMOR TREATMENT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii432-iii432
Author(s):  
Adeoye Oyefiade ◽  
Kiran Beera ◽  
Iska Moxon-Emre ◽  
Jovanka Skocic ◽  
Ute Bartels ◽  
...  
Keyword(s):  
White Matter ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Magnetic Resonance Images ◽  
Long Term Effects ◽  
Brain White Matter ◽  
The Right ◽  
Pediatric Brain ◽  
Betweeness Centrality

Abstract INTRODUCTION Treatments for pediatric brain tumors (PBT) are neurotoxic and lead to long-term deficits that are driven by the perturbation of underlying white matter (WM). It is unclear if and how treatment may impair WM connectivity across the entire brain. METHODS Magnetic resonance images from 41 PBT survivors (mean age: 13.19 years, 53% M) and 41 typically developing (TD) children (mean age: 13.32 years, 51% M) were analyzed. Image reconstruction, segmentation, and node parcellation were completed in FreeSurfer. DTI maps and probabilistic streamline generation were completed in MRtrix3. Connectivity matrices were based on the number of streamlines connecting two nodes and the mean DTI (FA) index across streamlines. We used graph theoretical analyses to define structural differences between groups, and random forest (RF) analyses to identify hubs that reliably classify PBT and TD children. RESULTS For survivors treated with radiation, betweeness centrality was greater in the left insular (p < 0.000) but smaller in the right pallidum (p < 0.05). For survivors treated without radiation (surgery-only), betweeness centrality was smaller in the right interparietal sulcus (p < 0.05). RF analyses showed that differences in WM connectivity from the right pallidum to other parts of the brain reliably classified PBT survivors from TD children (classification accuracy = 77%). CONCLUSIONS The left insular, right pallidum, and right inter-parietal sulcus are structurally perturbed hubs in PBT survivors. WM connectivity from the right pallidum is vulnerable to the long-term effects of treatment for PBT.

Abstract TMP56: Differential Effect of Left versus Right White Matter Hyperintensity Burden on Functional Decline: The Northern Manhattan Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mandip S Dhamoon ◽  
Ying-Kuen Cheung ◽  
Ahmet M Bagci ◽  
Dalila Varela ◽  
Noam Alperin ◽  
...  
Keyword(s):  
White Matter ◽  
Large Population ◽  
Functional Decline ◽  
Frontal Lobes ◽  
White Matter Hyperintensity ◽  
Periventricular White Matter ◽  
Parietal Lobes ◽  
Brain White Matter ◽  
The Right

Background: We previously showed that overall brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right WMHV asymmetry was associated with functional trajectories. Methods: In the Northern Manhattan MRI study, participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter) was determined separately by combining bimodal image intensity distribution and atlas based methods.. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years. Generalized estimating equations models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up. Results: Among 1195 participants, mean age was 71 (SD 9) years, 39% were male, 67% had hypertension and 19% diabetes. Greater WMHV asymmetry in the frontal lobes (-3.53 BI points per unit greater WMHV on the right compared to left, 95% CI -0.18, -6.88) and whole brain (-7.23 BI points, 95% CI 0.07, -14.54) was associated with lower overall function. Greater WMHV asymmetry in the frontal lobes (-0.74 additional BI points per year per unit greater WMHV on the right compared to left, 95% CI 0.05, -1.54) and parietal lobes (1.11 additional BI points per year, 95% CI 0.30, 1.93) was independently associated with accelerated functional decline. Periventricular WMHV asymmetry was not associated with function. Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline, especially with greater WMHV on the right. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional decline.

scholarly journals A Diffusion Tensor Imaging Study on the Phonology-related Pathways in Cantonese-mandarin Bilinguals.

2021 ◽  
Author(s):  
Xiaoyu Xu ◽  
Yuying Jin ◽  
Ning Pan ◽  
Muqing Cao ◽  
Jin Jing ◽  
...  
Keyword(s):  
White Matter ◽  
Phonological Processing ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Study ◽  
Brain White Matter ◽  
The Mean ◽  
The Right ◽  
Long Term Experience

Abstract Cantonese and Mandarin are logographic languages, and the phonology is the main difference between the two languages. It is unclear whether long-term experience of Cantonese-Mandarin bilingualism will shape different brain white matter structures of pathways related to phonological processing. 30 Cantonese-Mandarin bilinguals and 30 Mandarin monolinguals completed diffusion-weighted imaging (DWI) scans and phonological processing tasks. The tractography and TBSS were used to investigate the structural differences in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) between Cantonese-Mandarin bilinguals and Mandarin monolinguals. Post-hoc correlation analysis was conducted to investigate the relationship between the different structures with phonological processing skills. Compared to the Mandarin monolinguals, the Cantonese-Mandarin bilinguals had higher fractional anisotropy (FA) along the left ILF, higher mean diffusivity (MD) in the clusters along the temporoparietal segment of SLF (tSLF), as well as higher axial diffusivity (AD) in the right tSLF, IFOF, bilateral ILF. The mean AD of the different voxels in the right IFOF and the mean FA of the different voxels in the left ILF were positively correlated with the inverse efficiency score (IES) of the Cantonese auditory and Mandarin visual rhyming judgment tasks respectively within the bilingual group. Long-term experience of Cantonese-Mandarin bilinguals shape different brain white matter structures including right tSLF, IFOF, bilateral ILF. The bilinguals’ white matter showed higher diffusivity, especially in the axonal direction, than the monolinguals. These changes were related to bilinguals’ phonological processing.

Management and Surveillance of Short- and Long-Term Sequelae of Radiation Therapy for the Treatment of Pediatric Brain Tumors

2020 ◽  
Vol 18 (06) ◽  
pp. 307-312
Author(s):  
Fred Chiu-Lai Lam ◽  
Ekkehard M Kasper ◽  
Anand Mahadevan
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Pediatric Brain Tumors ◽  
Special Edition ◽  
Long Term Effects ◽  
Transition Into Adulthood ◽  
Short And Long Term ◽  
Pediatric Brain

AbstractRadiation therapy (RT) is a mainstay for the treatment of pediatric brain tumors. As improvements in and sophistication of this modality continue to increase the survival of patients, the long-term sequelae of RT pose significant challenges in the clinical management of this patient population as they transition into adulthood. In this special edition, we review the short- and long-term effects of RT for the treatment of pediatric brain tumors and the necessary surveillance required for follow-up.

scholarly journals NIMG-56. A MULTIMODAL 7 TELSA MRI INVESTIGATION OF LONG-TERM EFFECTS OF RADIOTHERAPY ON THE ADOLESCENT BRAIN & COGNITION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi173-vi174 ◽  
Author(s):  
Melanie Morrison ◽  
Sivakami Avadiappan ◽  
Justin Yuan ◽  
Schuyler Stoller ◽  
Angela Jakary ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
White Matter ◽  
Vascular Injury ◽  
7 Tesla ◽  
Long Term Effects ◽  
Whole Brain ◽  
Serial Imaging ◽  
Brain White Matter

Abstract INTRODUCTION Radiation therapy (RT) remains an integral role in the treatment of adolescent brain tumors, despite evidence of its long-term effects including cognitive impairment, vascular injury and reduced white matter integrity. While prior studies have related vascular injury to cognitive decline and associated more severe cognitive impairment with a whole-brain versus a focal RT approach, the relationship between underlying imaging, clinical, and treatment parameters has yet to be explored in this population. In this study we used multimodal 7 Tesla MR imaging to probe RT-induced changes in the brain and identified risk factors for clinical outcome. METHODS Twenty-three patients (age 6–25 years) with non-supratentorial tumors treated with RT as children and 4 nonirradiated control patients (ages 13–16 years) were scanned on a 7T MRI system; eight patients underwent serial imaging 0.9–3.7 years following the first scan. Simultaneous MR-veniography and angiography, and 90-direction, dual-shell multi-band diffusion MRI were used to assess the relationships among cerebral microbleed (CMB) development, changes in arterial radii, and whole-brain white matter connectivity. A computerized cognitive battery (Cogstate) evaluated multiple domains of cognitive function. Multiple univariate and multivariate regression models with multiple comparison corrections identified risk factors. RESULTS Cognitive status measured via executive function and working memory tasks revealed the strongest associations with type of RT and imaging parameters. Specific risk factors for worse outcome included whole-brain RT, RT at a younger age, and time since RT. On imaging this corresponded to increased CMB burden, decreased arterial volume, and reduced global structural connectivity; intrasubject serial imaging followed these trends. CONCLUSION 7T-MRI was highly sensitive to CMBs with cumulative incidence rates greatly exceeding prior 3T studies in this population. This work demonstrates the value of multimodal 7T-MRI in providing metrics that reflect cognitive deficits arising from RT and identifying patients who would benefit the most from cognitive rehabilitation.

Investigating The Long–Term Effects Of Preterm Birth On Brain White Matter Using Diffusion Tensor Imaging

NeuroImage ◽  
2009 ◽  
Vol 47 ◽  
pp. S46
Author(s):  
Z Nagy ◽  
J Ashburner ◽  
J Andersson ◽  
S Jbabdi ◽  
B Draganski ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Preterm Birth ◽  
White Matter ◽  
Diffusion Tensor ◽  
Long Term Effects ◽  
Brain White Matter

scholarly journals A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiqun Zhang ◽  
Fengju Chen ◽  
Lawrence A. Donehower ◽  
Michael E. Scheurer ◽  
Chad J. Creighton
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tyrosine Kinases ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Altered Expression ◽  
Critical Pathways ◽  
Cis Regulation ◽  
Or Gene ◽  
Pediatric Brain

AbstractThe global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children’s Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.

scholarly journals DIPG-60. PILOT STUDY OF CIRCULATING TUMOR CELLS IN PEDIATRIC HIGH GRADE BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii299-iii299
Author(s):  
Wafik Zaky ◽  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Izhar Bath ◽  
Sofia Yi ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Disease Assessment ◽  
Liquid Biopsies ◽  
Capture Method ◽  
Pediatric Brain

Abstract BACKGROUND Despite its increasing use, circulating tumor cells (CTCs) have not been studied in pediatric brain tumors. METHODS Cell surface vimentin (CSV) is a marker for CTC detection. We developed an automated CSV-based CTC capture method for pediatric brain tumor using the Abnova Cytoquest platform. PBMCs isolated from blood samples from 52 brain tumor patients were processed to isolate CSV+ CTCs. Captured cells were then stained for CSV and CD45 and scanned to determine the number of CTCs. DIPG samples were additionally examined for H3K27M expression on CSV+ cells. Long term cancer survivors were used as a control cohort. RESULTS 86.4% of all the samples exhibited between 1–13 CSV+ CTCs, with a median of 2 CSV+ CTCs per sample. Using a value of ≥ 1 CTC as a positive result, the sensitivity and specificity of this test was 83.05% and 60.0% respectively. 19 DIPG samples were analyzed and 70% (13 samples) were positive for 1–5 CTCs. Five of these 7 positive CSV+ CTCs DIPG samples were also positive for H3K27M mutations by immunohistochemistry (71%). Mean survival in days for the CTC positive and negative DIPG samples were 114 and 211 days, respectively (p= 0.13). CONCLUSION This is the first study of CTCs in pediatric CNS tumors using an automated approach. Patients with brain tumors can exhibit CSV+ CTCs within peripheral blood. The use of specific molecular markers such as H3K27M can improve the diagnostic capability of liquid biopsies and may enable future disease assessment for personalized therapy.

scholarly journals EPEN-33. PHARMACOGENOMICS REVEALS SYNERGISTIC INHIBITION OF ERBB2 AND PI3K SIGNALING AS A THERAPEUTIC STRATEGY FOR EPENDYMOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii314-iii314
Author(s):  
David Pauck ◽  
Eunice Paisana ◽  
Rita Cascão ◽  
Sevgi Sarikaya-Seiwert ◽  
Viktoria Marquardt ◽  
...  
Keyword(s):  
Primary Cultures ◽  
Single Agent ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Primary Diagnosis ◽  
High Throughput Drug Screening ◽  
Established Cell ◽  
Set Up ◽  
Pediatric Brain

Abstract Subgroups of ependymoma, especially RELA fusion-positive and posterior fossa type A tumors, are associated with poor prognosis. Curative therapeutic strategies have not yet been identified. We set up a high-throughput drug screening (HTS) pipeline to evaluate clinically established compounds (n=196) in primary ependymoma cultures (n=12). As culturing ependymoma is challenging, assay miniaturization to 1536-well microplates emerged as a key feature to process HTS despite smallest cell numbers. DNA methylation profiling showed that entity and subgroup affiliation from primary diagnosis was maintained in primary cultures, as assessed through molecular neuropathology 2.0 based classification (MNP 2.0, Capper, D. et al., Nature, 2018). A comparison of HTS data of ependymoma and other pediatric brain tumor models (n=48) revealed a remarkable chemoresistance in vitro. However, we identified Neratinib, an irreversible ERBB2 inhibitor, as the most prominent candidate which was preferentially active in a subset of the investigated ependymoma cultures (n=5). Combinatory treatment with Copanlisib, a PI3K inhibitor, was able to overcome resistance to single agent treatment using Neratinib in established cell lines of ependymoma (n=3) and 2/4 primary cultures for which combinatory treatment could be tested. Finally, we validated efficacy of Neratinib combined with Copanlisib in mice bearing ependymoma xenografts which revealed significantly reduced tumor size compared to vehicle-treated animals. In summary, our study demonstrates that HTS may reveal targeted therapies for pediatric brain tumors. Specifically, we found a synergistic interaction of Neratinib and Copanlisib for treatment of ependymoma, thereby providing a novel therapeutic approach in an otherwise largely chemoresistant entity.

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