Abstract WP192: Periventricular White Matter Hyperintensities Are Associated With Functional Decline: The Northern Manhattan Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mandip S Dhamoon ◽  
Ying-Kuen Cheung ◽  
Ahmet M Bagci ◽  
Chensy Marquez ◽  
Noam Alperin ◽  
...  
Keyword(s):  
White Matter ◽  
Repeated Measures ◽  
Brain Mri ◽  
Large Population ◽  
Functional Decline ◽  
Brain Regions ◽  
White Matter Hyperintensity ◽  
Periventricular White Matter ◽  
Brain White Matter

Background: We previously showed that overall brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. However, it was unclear whether WMHV in particular brain regions was more predictive of decline. We hypothesized that WMHV in particular brain regions would be more predictive of functional decline. 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 [PVWM]) 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 and were followed for stroke and myocardial infarction (MI). Due to multiple collinear variables, lasso regression was used to select regional WMHV variables, and adjusted generalized estimating equations models estimated associations with baseline BI and change over time. Results: Among 1195 participants, mean age was 71 (SD 9) years, 460 (39%) were male, 802 (67%) had hypertension and 224 (19%) diabetes. Using lasso regularization, only right anterior PVWM was selected, and each SD increase was associated with accelerated functional decline, of -0.95 additional BI points per year (95% CI -1.20, -0.70) in an unadjusted model, -0.92 points per year (95% CI -1.18, -0.67) with baseline covariate adjustment, and -0.87 points per year (95% CI -1.12, -0.62) after adjusting for stroke and MI. This decline was in addition to a mean decline of -1.13 (95% CI -1.29, -0.97), -1.19 (95% CI -1.36, -1.01), and -1.04 (95% CI -1.21, -0.88) BI points per year, respectively. Conclusions: In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline. Periventricular WMHV may have a greater effect on mobility due to dysfunction in descending leg motor tracts.

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.

The Clinical Value of Periventricular White Matter Hyperintensity on MRI in Sudden Sensorineural Hearing Loss

2021 ◽  
pp. 000348942110189
Author(s):  
Jung Woo Lee ◽  
Deoksu Kim ◽  
Seokhwan Lee ◽  
Sung-Won Choi ◽  
Soo-Keun Kong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Multivariate Analysis ◽  
White Matter ◽  
Brain Mri ◽  
Sudden Sensorineural Hearing Loss ◽  
White Matter Hyperintensity ◽  
Control Group ◽  
Periventricular White Matter ◽  
Clinical Value ◽  
Hearing Gain

Objectives: To assess the clinical value of periventricular white matter hyperintensity (PWMH) found on brain magnetic resonance imaging (MRI) in patients with sudden sensorineural hearing loss (SSNHL). Methods: In this prospective study, 115 patients who were diagnosed with SSNHL aged between 55 and 75 years were analyzed. All subjects underwent brain MRI and were divided into a PWMH and control groups, depending on the presence of PWMH on MRI. PWMH was subdivided into 3 groups according to severity. Pure-tone average results and hearing gain were compared between the 2 groups before treatment and 2 months after treatment. Hearing improvement was assessed using Sigel’s criteria. Results: A total of 106 patients (43 in the PWMH group and 63 in the control group) finally completed the 2-month follow-up. Average hearing gain in the PWMH group was significantly higher than in the control group (34.8 ± 20.3 and 25.9 ± 20.3, respectively, P = .029). PWMH score 1 showed significantly better hearing levels and hearing gain compared to PWMH score 3 and the control group. Multivariate analysis revealed that younger age, better initial hearing level, and the presence of PVWM score 1 were associated with good recovery. Conclusions: The presence of PWMH score 1 on brain MRI in patients with SSNHL was associated with better treatment response and was a good prognostic factor in a multivariate analysis while the hearing recovery in more severe PWMH (scores 2, 3) was not different from the control group.

scholarly journals Association of White Matter Hyperintensity Markers on MRI and Long-term Risk of Mortality and Ischemic Stroke

Neurology ◽  
2021 ◽  
Vol 96 (17) ◽  
pp. e2172-e2183 ◽  
Author(s):  
Rashid Ghaznawi ◽  
Mirjam I. Geerlings ◽  
Myriam Jaarsma-Coes ◽  
Jeroen Hendrikse ◽  
Jeroen de Bresser ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Cox Regression ◽  
Brain Mri ◽  
Arterial Disease ◽  
White Matter Hyperintensity ◽  
Risk Of Mortality ◽  
Mri Scans

ObjectiveTo determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke.MethodsWe included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease.ResultsWe included 999 patients (59 ± 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2–16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13–1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26–1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01–2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05–1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03–1.42) and ischemic stroke (HR 1.28, 95% CI 1.05–1.55).ConclusionsWMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.

Abstract P121: Twenty-two-year Cognitive Decline Was Significantly Associated With Vascular And Neurodegenerative Brain Changes In The Aric Neurocognitive Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Alessandro Orlando ◽  
A Richey Sharrett ◽  
Rebecca F Gottesman ◽  
David Knopman ◽  
Andrea L Schneider ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Imaging ◽  
Temporal Lobe ◽  
Brain Volume ◽  
Brain Mri ◽  
Amyloid Deposition ◽  
White Matter Hyperintensity ◽  
Β Amyloid ◽  
The Mean

Introduction: Studies have found that smaller brain volumes, cerebral infarcts, and white matter abnormalities are associated with dementia and mild cognitive impairment. However, these studies have been limited by short follow-up precluding a strong establishment of temporality. Therefore, it is unknown whether brain imaging findings are preceded by long-term changes in cognition. We sought to address this gap by examining brain imaging and two decades of cognitive changes in and a large, representative population-based cohort of older adults of black and white race. Hypothesis: We hypothesized that 22-year declines in global cognitive factor scores (GCFS) would be associated with a pattern of smaller total brain and temporal lobe meta region of interest (likely to be affected by Alzheimer’s disease) volumes, larger white matter hyperintensity volumes, and greater odds of ≥1 lacunar infarct and elevated brain β-amyloid deposition. Methods: ARIC participants with brain imaging data, complete cognitive factor score, and not missing key covariates were included. GCFS were collected at three visits across 22 years (1990-2013), and brain MRI and florbetapir PET imaging were collected in 2011-13; PET in subset of n=327. Mixed effects models with random intercepts and slopes predicted individual change in GCFS. Outcomes of interest were total brain volume (cc), temporal lobe meta region volume, log 2 (white matter hyperintensity volume), ≥1 lacunar infarct, and elevated brain β-amyloid deposition (SUVR >1.2). Multivariable linear and logistic regression was used to relate outcomes to GCFS slopes after adjusting for confounders, including vascular risk factors. As appropriate, models were also adjusted for total intracranial volume. Results: Among 1957 with complete brain MRI imaging, 1830 were included in the study, 60% (n=1096) women and 26% (n=480) black. At the first visit, the mean (SD) baseline age was 55 (5.2) yrs. The mean (SD) observed GCFS at the three visits were 0.16 (0.79), 0.05 (0.75), and -0.78 (0.86). After adjustment, a 1-SD larger decline in GCFS was significantly associated with a smaller brain volume by 1.6% [95%CI: 1.3, 1.8] relative to mean brain volume, a smaller temporal lobe meta region volume by 2.4% [2.1, 2.8] relative to the mean volume, a 15% [11, 19] larger volume of white matter hyperintensities, 1.3-fold [1.2, 1.4] higher odds of having ≥1 lacune, and 1.8-fold [1.4, 2.4] higher odds of elevated brain β-amyloid deposition. Associations remained significant after further adjustment for first or last GCFS. Conclusions: Greater declines in long-term cognitive functioning were significantly associated with smaller brain volumes and dementia-related brain characteristics and were independent of last visit GCFS. This suggests long-term changes in cognition may precede late-life brain morphology and outperform cross-sectional cognitive measures.

scholarly journals Fluctuating Asymmetry and Individual Variation in Regional Gray and White Matter Volumes: A Voxel-Based Morphometry Study

2008 ◽  
Vol 6 (4) ◽  
pp. 147470490800600 ◽  
Author(s):  
Matthew Euler ◽  
Robert J. Thoma ◽  
Lauren Parks ◽  
Steven W. Gangestad ◽  
Ronald A. Yeo
Keyword(s):  
White Matter ◽  
Fluctuating Asymmetry ◽  
Gray Matter Volume ◽  
Brain Mri ◽  
Brain Regions ◽  
Voxel Based Morphometry ◽  
Whole Brain ◽  
Matter Volume ◽  
Brain White Matter ◽  
Mri Scans

Composite measures of fluctuating asymmetry (FA) of skeletal features are commonly used to estimate developmental instability (DI), the imprecise expression of developmental design due to perturbations during an individual's growth and maturation. Though many studies have detailed important behavioral correlates of FA, very little is known about its possible neuroanatomical correlates. In this study we obtained structural brain MRI scans from 20 adults and utilized voxel-based morphometry (VBM) to identify specific regions linked to FA. Greater FA predicted greater whole brain white matter volume, and a trend in the same direction was noted for whole brain gray matter volume. Greater FA was associated with significantly greater gray and white matter volumes in discrete brain regions, most prominently in the frontal lobes and in the right cerebral hemisphere. Developmental studies are needed to identify when FA-related brain differences emerge and to elucidate the specific neurobiological mechanisms leading to these differences.

scholarly journals White matter microstructural abnormalities in euthymic bipolar disorder

2010 ◽  
Vol 196 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Karine A. N. Macritchie ◽  
Adrian J. Lloyd ◽  
Mark E. Bastin ◽  
Kamini Vasudev ◽  
Peter Gallagher ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Substance Use ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
Brain Regions ◽  
White Matter Hyperintensity ◽  
Sign Test ◽  
Periventricular White Matter ◽  
Diffusion Parameters

BackgroundAbnormal diffusion parameters are reported in specific brain regions and white matter tracts in bipolar disorder.AimsTo investigate whether these abnormalities are generalised, and thus evident in large regions of white matter.MethodDiffusion parameters were measured at several regions in the corpus callosum and in deep/periventricular white matter in 28 currently euthymic patients with bipolar disorder and controls. White matter hyperintensity loads were assessed.ResultsComparing the whole data-sets using the sign test, in the group with bipolar disorder, mean diffusivity was greater at all 15 sites (P<0.001) and fractional anisotropy was reduced at 13 (P<0.01). The effect of diagnosis was significant for callosal mean diffusivity and fractional anisotropy and for deep/periventricular mean diffusivity (MANCOVA). Comparing individual regions (Mann–Whitney U-test), prefrontal and periventricular mean diffusivity were significantly increased; callosal and occipital fractional anisotropy were significantly reduced. Former substance use and lithium were possible confounding factors. Periventricular white matter hyperintensities were associated with significantly increased periventricular mean diffusivity in individuals with bipolar disorder.ConclusionsGeneralised white matter microstructural abnormalities may exist in bipolar disorder, possibly exacerbated by past substance use and ameliorated by lithium.

scholarly journals Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI

Neurology ◽  
2019 ◽  
Vol 93 (9) ◽  
pp. e917-e926 ◽  
Author(s):  
Frank J. Wolters ◽  
Hazel I. Zonneveld ◽  
Silvan Licher ◽  
Lotte G.M. Cremers ◽  
M. Kamran Ikram ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Perfusion ◽  
Brain Mri ◽  
Structural Connectivity ◽  
Mean Diffusivity ◽  
Population Based ◽  
White Matter Hyperintensity ◽  
Dementia Risk ◽  
Increased Risk

ObjectiveTo determine the long-term association of hemoglobin levels and anemia with risk of dementia, and explore underlying substrates on brain MRI in the general population.MethodsSerum hemoglobin was measured in 12,305 participants without dementia of the population-based Rotterdam Study (mean age 64.6 years, 57.7% women). We determined risk of dementia and Alzheimer disease (AD) (until 2016) in relation to hemoglobin and anemia. Among 5,267 participants without dementia with brain MRI, we assessed hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion.ResultsDuring a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. We observed a U-shaped association between hemoglobin levels and dementia (p = 0.005), such that both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio [95% confidence interval (CI)], lowest vs middle quintile 1.29 [1.09–1.52]; highest vs middle quintile 1.20 [1.00–1.44]). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia (95% CI 11%–62%) and 41% (15%–74%) for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume (p = 0.03), and structural connectivity (for mean diffusivity, p < 0.0001), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion (p < 0.0001).ConclusionLow and high levels of hemoglobin are associated with an increased risk of dementia, including AD, which may relate to differences in white matter integrity and cerebral perfusion.

scholarly journals Baseline NAWM structural integrity and CBF predict periventricular WMH expansion over time

Neurology ◽  
2018 ◽  
Vol 90 (24) ◽  
pp. e2119-e2126 ◽  
Author(s):  
Nutta-on Promjunyakul ◽  
Hiroko H. Dodge ◽  
David Lahna ◽  
Erin L. Boespflug ◽  
Jeffrey A. Kaye ◽  
...  
Keyword(s):  
White Matter ◽  
Structural Integrity ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Estimating Equation ◽  
White Matter Hyperintensity ◽  
Periventricular White Matter ◽  
Normal Appearing White Matter ◽  
Over Time

ObjectiveWe aimed to describe and compare baseline cerebral blood flow (CBF) and microstructural characteristics of normal-appearing white matter (NAWM) within the vulnerable periventricular white matter hyperintensity (PVWMH) penumbra region in predicting white matter hyperintensity (WMH) growth over time.MethodsFifty-two patients, aged 82.8 years, underwent serial brain MRI, including pulsed arterial spin labeling and diffusion tensor imaging (DTI). New WMH and persistent NAWM voxels in relation to WMH penumbra at follow-up were identified. Mean baseline CBF and DTI variables of the new WMH and persistent NAWM voxels were computed. Univariate analyses with paired t tests were performed. Generalized estimating equation analyses were used to compare the relationships of baseline CBF, and structural penumbras with WMH growth, controlling for confounders.ResultsLow baseline CBF and fractional anisotropy, and high mean diffusivity (MD), were independently associated with new PVWMH voxels, with MD being the best predictor of WMH growth. A separate model demonstrated that radial diffusivity had the strongest relationship with WMH growth compared with CBF and axial diffusivity.ConclusionCBF and DTI measures independently predict WMH growth over time. DTI is a more sensitive predictor of WMH growth than CBF, with WMH progression likely due to demyelinating injury secondary to low perfusion. Findings support the use of MD as a sensitive marker of NAWM vulnerability in future trials aimed at preserving WM integrity.

Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

2019 ◽  
Vol 24 (2) ◽  
pp. 200-208
Author(s):  
Ravindra Arya ◽  
Francesco T. Mangano ◽  
Paul S. Horn ◽  
Sabrina K. Kaul ◽  
Serena K. Kaul ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Hippocampal Sclerosis ◽  
Brain Mri ◽  
Temporal Lobectomy ◽  
Seizure Freedom ◽  
Seizure Onset

OBJECTIVEThere is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.METHODSChildren who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.RESULTSOne hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.CONCLUSIONSA lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

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 &lt; 0.000) but smaller in the right pallidum (p &lt; 0.05). For survivors treated without radiation (surgery-only), betweeness centrality was smaller in the right interparietal sulcus (p &lt; 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.

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