Multimodal Deep Learning Improves Recurrence Risk Prediction in Pediatric Low-Grade Gliomas.

Background: Postoperative recurrence risk for pediatric low-grade gliomas (pLGGs) is challenging to predict by conventional clinical, radiographic, and genomic factors. We investigated if deep learning of MRI tumor features could improve postoperative pLGG risk stratification.

Methods: We used pre-trained deep learning (DL) tool designed for pLGG segmentation to extract pLGG imaging features from preoperative T2-weighted MRI from patients who underwent surgery (DL-MRI features).

Stepwise Transfer Learning for Expert-level Pediatric Brain Tumor MRI Segmentation in a Limited Data Scenario.

Purpose To develop, externally test, and evaluate clinical acceptability of a deep learning pediatric brain tumor segmentation model using stepwise transfer learning. Materials and Methods In this retrospective study, the authors leveraged two T2-weighted MRI datasets (May 2001 through December 2015) from a national brain tumor consortium ( = 184; median age, 7 years [range, 1-23 years]; 94 male patients) and a pediatric cancer center ( = 100; median age, 8 years [range, 1-19 years]; 47 male patients) to develop and evaluate deep learning neural networks for pediatric low-grade glioma segmentation using a stepwise transfer learning approach to maximize performance in a limited data scenario. The best model was externally tested on an independent test set and subjected to randomized blinded evaluation by three clinicians, wherein they assessed clinical acceptability of expert- and artificial intelligence (AI)-generated segmentations via 10-point Likert scales and Turing tests.

Noninvasive Molecular Subtyping of Pediatric Low-Grade Glioma with Self-Supervised Transfer Learning.

Purpose To develop and externally test a scan-to-prediction deep learning pipeline for noninvasive, MRI-based mutational status classification for pediatric low-grade glioma. Materials and Methods This retrospective study included two pediatric low-grade glioma datasets with linked genomic and diagnostic T2-weighted MRI data of patients: Dana-Farber/Boston Children's Hospital (development dataset, = 214 [113 (52.8%) male; 104 (48.

Automated temporalis muscle quantification and growth charts for children through adulthood.

Lean muscle mass (LMM) is an important aspect of human health. Temporalis muscle thickness is a promising LMM marker but has had limited utility due to its unknown normal growth trajectory and reference ranges and lack of standardized measurement. Here, we develop an automated deep learning pipeline to accurately measure temporalis muscle thickness (iTMT) from routine brain magnetic resonance imaging (MRI).

Noninvasive molecular subtyping of pediatric low-grade glioma with self-supervised transfer learning.

Purpose: To develop and externally validate a scan-to-prediction deep-learning pipeline for noninvasive, MRI-based BRAF mutational status classification for pLGG.

Materials And Methods: We conducted a retrospective study of two pLGG datasets with linked genomic and diagnostic T2-weighted MRI of patients: BCH (development dataset, n=214 [60 (28%) BRAF fusion, 50 (23%) BRAF V600E, 104 (49%) wild-type), and Child Brain Tumor Network (CBTN) (external validation, n=112 [60 (53%) BRAF-Fusion, 17 (15%) BRAF-V600E, 35 (32%) wild-type]). We developed a deep learning pipeline to classify BRAF mutational status (V600E vs.

Expert-level pediatric brain tumor segmentation in a limited data scenario with stepwise transfer learning.

Purpose: Artificial intelligence (AI)-automated tumor delineation for pediatric gliomas would enable real-time volumetric evaluation to support diagnosis, treatment response assessment, and clinical decision-making. Auto-segmentation algorithms for pediatric tumors are rare, due to limited data availability, and algorithms have yet to demonstrate clinical translation.

Methods: We leveraged two datasets from a national brain tumor consortium (n=184) and a pediatric cancer center (n=100) to develop, externally validate, and clinically benchmark deep learning neural networks for pediatric low-grade glioma (pLGG) segmentation using a novel in-domain, stepwise transfer learning approach.

Changes in Bone Marrow Adipose Tissue in Transgender and Gender Non-Conforming Youth Undergoing Pubertal Suppression: A Pilot Study.

Pubertal suppression with gonadotropin-releasing hormone (GnRH) agonists in transgender and gender non-conforming (TGNC) youth may affect acquisition of peak bone mass. Bone marrow adipose tissue (BMAT) has an inverse relationship with bone mineral density (BMD). To evaluate the effect of pubertal suppression on BMAT, in this pilot study we prospectively studied TGNC youth undergoing pubertal suppression and cisgender control participants with similar pubertal status over a 12-month period.

Bone marrow adiposity in pediatric Crohn's disease.

Patients with Crohn's disease often have low bone mineral density and an increased risk of osteoporosis. Although decreased bone formation can be seen at diagnosis, the underlying pathophysiology of suboptimal bone accrual remains poorly understood. We sought to evaluate a novel mechanism affecting osteogenesis in patients with Crohn's disease.

Bone density and bone marrow composition in transgender girls prior to pubertal blockade: A case series.

Purpose: To determine bone mineral density (BMD) of transgender girls before pubertal blockade, and correlate with lifestyle and clinical variables.

Methods: Six transfemale peri-pubertal girls had knee magnetic resonance imaging (MRI) with T1-weighted images and single-voxel proton magnetic resonance spectroscopy (MRS). BMD measurements were obtained via dual-energy X-ray absorptiometry.

Quantifying radiation therapy response using apparent diffusion coefficient (ADC) parametric mapping of pediatric diffuse intrinsic pontine glioma: a report from the pediatric brain tumor consortium.

Background And Purpose: Baseline diffusion or apparent diffusion coefficient (ADC) characteristics have been shown to predict outcome related to DIPG, but the predictive value of post-radiation ADC is less well understood. ADC parametric mapping (FDM) was used to measure radiation-related changes in ADC and compared these metrics to baseline ADC in predicting progression-free survival and overall survival using a large multi-center cohort of DIPG patients (Pediatric Brain Tumor Consortium-PBTC).

Materials And Methods: MR studies at baseline and post-RT in 95 DIPG patients were obtained and serial quantitative ADC parametric maps were generated from diffusion-weighted imaging based on T2/FLAIR and enhancement regions of interest (ROIs).

Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa.

Purpose: Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy.

Methods: Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs.

Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic resonance imaging and magnetic resonance spectroscopy assessment.

Background: Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts.

Objective: The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa.

Materials And Methods: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE.

Correlation of F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

The purpose of this study was to describe baseline F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Baseline brain F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images.

Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium.

Background: Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT).

Methods: Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest.

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors.

Background: Cediranib (AZD2171), an oral pan-vascular endothelial growth factor (VEGF) inhibitor, was evaluated in this phase I study to determine its toxicity profile, dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics in children and adolescents with recurrent or refractory primary central nervous system (CNS) tumors.

Methods: Children and adolescents <22 years were enrolled into one of two strata: stratum I—those not receiving enzyme-inducing anticonvulsant drugs (EIACD) and stratum II—those receiving EIACDs. Dose-level selection was based on the continual reassessment method (CRM).

Pediatric brain tumor consortium multisite assessment of apparent diffusion coefficient z-axis variation assessed with an ice-water phantom.

Rationale And Objectives: Magnetic resonance diffusion imaging can characterize physiologic characteristics of pediatric brain tumors used to assess therapy response. The purpose of this study was to assess the variability of the apparent diffusion coefficient (ADC) along z-axis of scanners in the multicenter Pediatric Brain Tumor Consortium (PBTC).

Materials And Methods: Ice-water diffusion phantoms for each PBTC site were distributed with a specific diffusion imaging protocol.

White matter microstructure and cognition in adolescents with congenital heart disease.

Objective: To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA).

Study Design: We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing.

18F-FDG PET and MR imaging associations across a spectrum of pediatric brain tumors: a report from the pediatric brain tumor consortium.

Unlabelled: The purpose of this study was to describe (18)F-FDG uptake across a spectrum of pediatric brain tumors and correlate (18)F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS).

Methods: A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics.

Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a Pediatric Brain Tumor Consortium study.

Background: A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival.

Methods: Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9).

Exploratory evaluation of MR permeability with 18F-FDG PET mapping in pediatric brain tumors: a report from the Pediatric Brain Tumor Consortium.

Unlabelled: The purpose of this study was to develop a method of registering (18)F-FDG PET with MR permeability images for investigating the correlation of (18)F-FDG uptake, permeability, and cerebral blood volume (CBV) in children with pediatric brain tumors and their relationship with outcome.

Methods: Twenty-four children with brain tumors in a phase II study of bevacizumab and irinotecan underwent brain MR and (18)F-FDG PET within 2 wk. Tumor types included supratentorial high-grade astrocytoma (n = 7), low-grade glioma (n = 9), brain stem glioma (n = 4), medulloblastoma (n = 2), and ependymoma (n = 2).

Adolescents with D-transposition of the great arteries repaired in early infancy demonstrate reduced white matter microstructure associated with clinical risk factors.

Objective: Our objective was to use diffusion tensor imaging (DTI) to compare white matter microstructure in adolescents with D-transposition of the great arteries (D-TGA) who underwent the arterial switch operation in early infancy with typically developing control adolescents. We also examined correlates between patient demographic and medical risk factors and white matter as assessed by regional fractional anisotropy (FA) values.

Methods: We used with magnetic resonance imaging (MRI) to study 49 adolescents with D-TGA and 29 control adolescents.

Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma--a Pediatric Brain Tumor Consortium study.

A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in cases of pediatric recurrent ependymoma (EPN) to estimate sustained objective response rate and progression-free survival (PFS). Eligible patients received 2 doses of single-agent BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion-weighted and T1 dynamic contrast enhanced permeability imaging and tumor immunohistochemistry for vascular endothelial growth factor (VEGF)-A and -B, hypoxia inducible factor-2α, VEGF receptor (R)-2, and carbonic anhydrase (CA)-9.

The use of magnetic resonance imaging to predict ACL graft structural properties.

Magnetic resonance imaging (MRI) could potentially be used to non-invasively predict the strength of an ACL graft after ACL reconstruction. We hypothesized that the volume and T2 relaxation parameters of the ACL graft measured with MRI will predict the graft structural properties and anteroposterior (AP) laxity of the reconstructed knee. Nine goats underwent ACL reconstruction using a patellar tendon autograft augmented with a collagen or collagen-platelet composite.

MRI as a central component of clinical trials analysis in brainstem glioma: a report from the Pediatric Brain Tumor Consortium (PBTC).

We report MRI findings from 2 pediatric clinical trials of diffuse intrinsic brainstem glioma (BSG) incorporating concurrent radiation therapy (RT) with molecularly targeted agents (gefitinib and tipifarnib). We determined associations of MRI variables with progression-free survival and overall survival and investigated effects of treatment on these variables. MRI (including diffusion and perfusion) was done before treatment, every 8 weeks (first year), every 12 weeks (thereafter), and at the end of treatment or disease progression.

Evaluation of 18F-FDG PET and MRI associations in pediatric diffuse intrinsic brain stem glioma: a report from the Pediatric Brain Tumor Consortium.

Unlabelled: The purpose of this study was to assess (18)F-FDG uptake in children with a newly diagnosed diffuse intrinsic brain stem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS), and MRI indices.

Methods: Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: phase I/II study of gefitinib; PBTC-014: phase I/II study of tipifarnib). Baseline brain (18)F-FDG PET scans were obtained in 40 children in these trials.