Changes in indicators of cerebral metabolic stress following treatment with voxelotor in children and adolescents with sickle cell anemia.

Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin-oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction.

Connectivity of the Cerebello-Thalamo-Cortical Pathway in Survivors of Childhood Leukemia Treated With Chemotherapy Only.

Importance: Treatment with contemporary chemotherapy-only protocols is associated with risk for neurocognitive impairment among survivors of childhood acute lymphoblastic leukemia (ALL).

Objective: To determine whether concurrent use of methotrexate and glucocorticoids is associated with interference with the antioxidant system of the brain and damage and disruption of glucocorticoid-sensitive regions of the cerebello-thalamo-cortical network.

Design, Setting, And Participants: This cross-sectional study was conducted from December 2016 to July 2019 in a single pediatric cancer tertiary care center.

Developmental patterns of CBF and BOLD responses to visual stimulus.

To investigate the developmental changes of cerebral blood flow (CBF) and hemodynamic responses to changing neural activity, we used the arterial spin label (ASL) technique to measure resting CBF and simultaneous CBF / blood-oxygen-level dependent (BOLD) signal changes during visual stimulation in 97 typically developing children and young adults (age 13.35 [6.02, 25.

Neuroanatomical abnormalities related to dexamethasone exposure in survivors of childhood acute lymphoblastic leukemia.

Survivors of childhood acute lymphoblastic leukemia (ALL) treated with chemotherapy only are at risk for neurocognitive impairment. Regions of interest were identified a priori based on glucocorticoid receptor distribution, and sex-stratified multivariable linear regression models were used to test associations between brain MRI morphology and total number of intrathecal injections, and serum concentration of dexamethasone and methotrexate. Compared with controls, ALL survivors have persistently smaller volumes in the bilateral cerebellum (P < 0.

Cognitive Performance, Aerobic Fitness, Motor Proficiency, and Brain Function Among Children Newly Diagnosed With Craniopharyngioma.

Objectives: Craniopharyngioma survivors experience cognitive deficits that negatively impact quality of life. Aerobic fitness is associated with cognitive benefits in typically developing children and physical exercise promotes recovery following brain injury. Accordingly, we investigated cognitive and neural correlates of aerobic fitness in a sample of craniopharyngioma patients.

Ultrashort echo time imaging for quantification of hepatic iron overload: Comparison of acquisition and fitting methods via simulations, phantoms, and in vivo data.

Background: Current R2*-MRI techniques for measuring hepatic iron content (HIC) use various acquisition types and fitting models.

Purpose: To evaluate the accuracy and precision of R2*-HIC acquisition and fitting methods.

Study Type: Signal simulations, phantom study, and prospective in vivo cohort.

Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

Background: The impact of contemporary chemotherapy treatment for childhood acute lymphoblastic leukemia on central nervous system activity is not fully appreciated.

Methods: Neurocognitive testing and functional magnetic resonance imaging (fMRI) were obtained in 165 survivors five or more years postdiagnosis (average age = 14.4 years, 7.

Disseminability of computerized cognitive training: Performance across coaches.

Cogmed is a computerized cognitive intervention utilizing coaches who receive standardized instruction in analyzing training indices and tailoring feedback to remotely monitor participant's performance. The goal of this study was to examine adherence, satisfaction, and efficacy of Cogmed across coaches. Survivors of pediatric brain tumors and acute lymphoblastic leukemia (N = 68) were randomized to intervention (Cogmed) or waitlist control.

Overlapping Representation of Primary Tastes in a Defined Region of the Gustatory Cortex.

Both physiological and imaging approaches have led to often-disparate conclusions about the organization of taste information in gustatory cortex (GC). In this study, we used neuroanatomical and imaging approaches to delineate the likely area of insular cortex given to gustatory function and to characterize taste responses within this delineated area in female and male C57BL/6J mice. Anterograde tracers were injected into the taste thalamus (the medial parvicellular portion of the ventral posterior medial division, VPMpc) of mice and the thalamic terminal field was investigated across the cortex.

Disrupted development and integrity of frontal white matter in patients treated for pediatric medulloblastoma.

Background: Treatment of pediatric medulloblastoma is associated with known neurocognitive deficits that we hypothesize are caused by microstructural damage to frontal white matter (WM).

Methods: Longitudinal MRI examinations were collected from baseline (after surgery but before therapy) to 36 months in 146 patients and at 3 time points in 72 controls. Regional analyses of frontal WM volume and diffusion tensor imaging metrics were performed and verified with tract-based spatial statistics.

Long-Term Efficacy of Computerized Cognitive Training Among Survivors of Childhood Cancer: A Single-Blind Randomized Controlled Trial.

Objective: To investigate the long-term efficacy of computerized cognitive training in improving cognitive outcomes among childhood cancer survivors.

Methods: Sixty-eight survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) were randomly assigned to computerized cognitive intervention (23 ALL/11 BT, age = 12.21 ± 2.

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma.

Objective: Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy.

Methods: Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy.

Quantitative imaging analysis of posterior fossa ependymoma location in children.

Purpose: Imaging descriptions of posterior fossa ependymoma in children have focused on magnetic resonance imaging (MRI) signal and local anatomic relationships with imaging location only recently used to classify these neoplasms. We developed a quantitative method for analyzing the location of ependymoma in the posterior fossa, tested its effectiveness in distinguishing groups of tumors, and examined potential associations of distinct tumor groups with treatment and prognostic factors.

Methods: Pre-operative MRI examinations of the brain for 38 children with histopathologically proven posterior fossa ependymoma were analyzed.

Feasibility and acceptability of a remotely administered computerized intervention to address cognitive late effects among childhood cancer survivors.

Background: Childhood cancer survivors frequently develop working memory (WM) deficits as a result of disease and treatment. Medication-based and therapist-delivered interventions are promising but have limitations. Computerized interventions completed at home may be more appealing for survivors.

Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial.

Purpose: Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change.

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients.

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy.

Methods And Materials: Fifty-one patients (2.1-19.

Spatiotemporal Patterns of Tumor Occurrence in Children with Intraocular Retinoblastoma.

Purpose: To accurately map the retinal area covered by tumor in a prospectively enrolled cohort of children diagnosed with retinoblastoma.

Methods: Orbital MRI in 106 consecutive retinoblastoma patients (44 bilateral) was analyzed. For MRI-visible tumors, the polar angle and angle of eccentricity of points defining tumor perimeter on the retina were determined by triangulation from images in three orthogonal planes.

Functional MRI in medulloblastoma survivors supports prophylactic reading intervention during tumor treatment.

Development of reading skills is vulnerable to disruption in children treated for brain tumors. Interventions, remedial and prophylactic, are needed to mitigate reading and other learning difficulties faced by survivors. A functional magnetic resonance imaging (fMRI) study was conducted to investigate long-term effects of a prophylactic reading intervention administered during radiation therapy in children treated for medulloblastoma.

Clinical utility of the N-back task in functional neuroimaging studies of working memory.

Introduction: N-back tasks are commonly used in functional neuroimaging studies to identify the neural mechanisms supporting working memory (WM). Despite widespread use, the clinical utility of these tasks is not well specified. This study compared N-back performance during functional magnetic resonance imaging (fMRI) with task data acquired outside of the scanner as a measure of reliability across environment.

Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.

Comparing segmented ASL perfusion of vascular territories using manual versus semiautomated techniques in children with sickle cell anemia.

Purpose: Elevated cerebral blood flow (CBF) in sickle cell anemia (SCA) is an adaptive pathophysiologic response associated with decreased vascular reserve and increased risk for ischemia. We compared manual (M) and semiautomated (SA) vascular territory delineation to facilitate standardized evaluation of CBF in children with SCA.

Materials And Methods: ASL perfusion values from 21 children were compared for gray matter and white matter (WM) in vascular territories defined by M and SA delineation.

Quantitative longitudinal evaluation of diaschisis-related cerebellar perfusion and diffusion parameters in patients with supratentorial hemispheric high-grade gliomas after surgery.

Decreased cerebral blood volume (CBV) in contralateral cerebellar gray matter (cGM) in conjunction with cerebellar white matter (cWM) damage, consistent with crossed cerebro-cerebellar diaschisis (cCCD) develop following supratentorial hemispheric stroke. In this study, we investigated the longitudinal evolution of diaschisis-related cerebellar perfusion and diffusion tensor-imaging (DTI) changes in patients after surgery for supratentorial brain tumors. Eight patients (M:F 5:3, age 8-22 years) who received surgery for supratentorial high-grade gliomas were evaluated.

The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy.

Survivors of childhood brain tumors (BTs) treated with CNS-directed therapy show changes in cerebral white matter that are related to neurocognitive late effects. We examined the association between white matter volume and working memory ability in survivors treated with conformal radiation therapy (CRT). Fifty survivors (25 males, age at assessment = 13.

Incidental detection of late subsequent intracranial neoplasms with magnetic resonance imaging among adult survivors of childhood cancer.

Purpose: Survivors of childhood cancer are at an increased risk of developing subsequent neoplasms. In long-term survivors of childhood malignancies treated with and without cranial radiation therapy (CRT), undergoing unenhanced magnetic resonance imaging (MRI) of the brain, we estimated detection of intracranial neoplasms.

Methods: To investigate neurocognitive outcomes, 219 survivors of childhood cancer underwent unenhanced screening MRI of the brain.

Investigating the relationship between COMT polymorphisms and working memory performance among childhood brain tumor survivors.

Background: Survivors of childhood brain tumors are at increased risk for neurocognitive impairments, including deficits in abilities supported by frontal brain regions. Catechol-O-methyltransferase (COMT) metabolizes dopamine in the prefrontal cortex, with the Met allele resulting in greater dopamine availability and better performance on frontally mediated tasks compared to the Val allele. Given the importance of identifying resiliency factors against the emergence of cognitive late effects, the current study examined the relationship between COMT genotype and working memory performance among childhood brain tumor survivors.