Keywords: Adolescents, Brain

Motivation: Magnetic resonance elastography (MRE) sensitively captures structural changes in the brain. However, application of this technique has been limited to cross-sectional studies in adolescents.

Goal(s): Our aim was to examine, for the first time, longitudinal changes in MRE-derived brain tissue mechanical properties during adolescence.

Approach: Shear stiffness and damping ratio were calculated for 14 adolescents during two study visits separated by a year.

Results: Stiffness significantly decreased over one year. The largest stiffness declines were in subcortical gray matter, in agreement with cross-sectional studies. Changes in both shear stiffness and damping ratio were correlated with progression of puberty.

Impact: This longitudinal study found wide-spread softening of brain tissue during adolescence, supporting cross-sectional findings. These changes were also correlated with the progression of puberty. This confirms the sensitivity of mechanical properties to capture structural changes of brain maturation.

Keywords: Genetics, Normal development, screening; neonatal; brain connectivity; connectome; transcriptome

Motivation: Transcriptome, representing the set of gene expression, exhibits spatiotemporal heterogeneity during brain development, underlying the dramatic changes in brain structural connectivity as measured by diffusion MRI throughout development.

Goal(s): Our goal was to elucidate the association between macroscopic structural connectome and microscopic transcriptome across development.

Approach: Here, we revealed this dynamic association between structural connectome and gene expression from a large cohort of 336 participants from fetal stage to adulthood.

Results: The changes of associated genes’ enrichment in cell types, biological processes, cellular components, and molecular functions across different ages shed light into the dynamic transcriptomic roles in connectome maturation.

Impact: By associating transcriptome map from over 6500 protein-encoding genes and dMRI-derived structural network, we revealed spatiotemporally heterogeneous transcriptome-connectome association from fetal stage to adulthood, providing insights into genetically patterned process of brain topological changes in health and disease.

Keywords: Normal Development, Normal development, Infants, Myelination, Preterm, ASD

Motivation: Myelination in the human brain extends from late pregnancy to the end of adolescence. Yet, its developmental pattern during this period is not fully understand.

Goal(s): We use the BCP dataset to investigate early brain myelination between 0-6 years old.

Approach: We utilized T1-/T2-weighted intensity, a surrogate marker for myelin.

Results: We identified five spatial patterns with distinct developmental trajectories and investigated the biological implications of myelination on developmental diseases, finding that the myelin content of corpus callosum had a significant fully mediated effect on ASD-related indicators. Furthermore, we found an alternation of myelination development affected by preterm birth in a separate cohort.

Impact: We investigated myelination patterns in infants and toddlers by T1w/T2w based on the BCP dataset and identified five distinct regional developmental trajectories. Using a mediation analysis, we found an intrinsic association between myelination and ASD-related restricted repetitive behaviors.

Keywords: Normal Development, Pediatric

Motivation: Very preterm children have a risk of impaired cognitive function mediated by several risk factors. The association between structural alteration and high-order cognitive function remains unclear.

Goal(s): Very preterm children at 6 years old showed significant differences in cortical thickness associated with cognitive abilities compared with term infants.

Approach: Cortical thickness was assessed in 41 very preterm and 24 full-term children at 6 years of age. The cortical thickness analysis of structural T1-weighted images was performed using Advanced Normalization Tools.

Results: Perceptual reasoning indices, high-order cognitive function, were found to be broadly correlated with cortical thickness in both very preterm and term children
 

Impact: This study explores the between brain structure changes and cognitive abilities in very preterm and full-term children, providing insights for neurodevelopmental diagnosis.

Keywords: Normal Development, Brain, perfusion; global developmental delay; arterial spin labelling; cerebral blood flow

Motivation: Early detection of global developmental delay (GDD) in young children is imperative for effective intervention.

Goal(s): The goal of this study is to determine whether CBF values, measured through 3D-pcASL, can aid in early GDD diagnosis and intervention.

Approach: Twenty-six children with GDD and 13 age- and sex-matched healthy controls underwent 3D-T1 and 3D-pcASL imaging. CBF values in various brain regions were analyzed and compared using statistical tests.

Results: The study found significantly lower CBF values in the right occipital lobe and left basal ganglia in GDD children. CBF values in these regions demonstrated potential as diagnostic markers for GDD.

Impact: This study's findings suggest that 3D-pcASL perfusion imaging can aid in early diagnosis of global developmental delay (GDD) in young children. Detecting GDD through non-invasive imaging may enhance early intervention, ultimately improving developmental outcomes.

Keywords: Spectroscopy, Data Analysis, Neonatal, Data Acquisition, Data Processing

Motivation: The Healthy Brain and Child Development (HBCD) study is a longitudinal, multi-vendor, multi-site study of early brain development, which will enroll ~7,500 infants. HBCD includes MRS within the imaging protocol.

Goal(s): The goal of this abstract is to present HBCD MRS pilot data, and identify any vendor and site differences in MRS data quality and measured metabolite concentrations.

Approach: HBCD pilot MRS data were successfully acquired on 28 scanners, and analyzed using Osprey 2.5.0, to examine vendor and site differences.

Results: ANOVA results show minimal vendor and site differences which is encouraging for such a large-scale multi-site, multi-vendor study.

Impact: HBCD is an NIH-funded multicenter study of brain development across the first decade of life. It is the largest ever study to incorporate MRS. In this abstract, we present in vivo data demonstrating MRS performance across vendor and site. 

Keywords: Adolescents, Drug Development

Motivation: Medication response in adolescent depression is unpredictable and relationships between dose, brain concentrations and clinical response are unknown. 

Goal(s): ¹⁹F-MRS is uniquely suited to study pediatric brain disposition, as it’s non-invasive, non-radiolabeled and less than minimal risk. 

Approach: Youth (n=52) aged 12-21 taking fluoxetine completed ¹⁹F-MRS at 3T.

Results: Brain fluoxetine concentrations exceeded plasma concentrations by 9 to 304-fold. Dose-normalized brain concentrations varied 13-fold, explained by plasma concentration and dose with small contributions from BMI, CYP2D6 and ABCB1. ¹⁹F-MRS is a valuable tool for studying pediatric brain disposition of fluorine-containing medications and enables inquiry into patient factors that impact brain exposure and response.

Impact: In vivo 19F-MRS measures brain concentrations of fluorine-containing medications and enables inquiry into individual-level factors contributing to brain disposition. This approach fills a critical gap in pediatric drug development, especially where other imaging modalities (e.g., PET) are not feasible.

Keywords: Cancer, Cancer, survivorship, late effects, apnea, sleep

Motivation:  Survivors of pediatric Hodgkin’s lymphoma (HL) have excessive daytime sleepiness and fatigue, with substantial consequences to quality of life. Thoracic radiation therapy (TRT), traditionally used to treat HL, is associated with cardiopulmonary morbidity and may result in sleep apnea.

Goal(s): Although sleep is known to impact neurometabolites in the general population, its effect on neurometabolite concentrations in HL survivors has not been established.

Approach: The present study used magnetic resonance spectroscopy (MRS) to explore the relationship between neurometabolites and sleep quality in pediatric HL survivors and community controls.

Results: We found associations between metabolites associated with excitotoxicity and neuroinflammation with sleep and age.

Impact: Our findings may identify therapeutic targets for interventions that mitigate the treatment-related late effects commonly experienced by HL survivors. Our results suggest that excitotoxicity and neuroinflammation could mediate the impact of sleep disturbances on age-associated late effects of cancer treatment.

Keywords: Tumors (Pre-Treatment), Cancer, metabolism, spectroscopy

Motivation: Metabolic mapping in Diffuse intrinsic pontine glioma (DIPG) may indicate prognosis and potential therapeutic targets.

Goal(s): We intended to identify metabolic ratios that indicated dysregulated metabolic pathways using 1H-MRS and determine whether these metabolites are associated with overall survival length.

Approach: We performed CSI in patients with DIPG prior to radiation therapy. Then we assessed the predictive value of a metabolite ratio for patient overall survival.

Results: Lactate and total choline levels were found to be significantly associated with patient overall survival, making them potential prognostic predictors of overall survival in DIPG.

Impact: This study shows that more aggressive DIPGs are metabolically distinct from less aggressive tumors and that the metabolic differences can predict the overall survival of patients.

Keywords: Cancer, Radiomics

Motivation: Medulloblastoma (MB) is classified into different molecular (WNT, SHH, Group 3, and Group 4) subgroups. Accurate identification of molecular subgroups provides clinical value to the diagnosis of MB.

Goal(s): We aim to combine APT MRI and radiomic analysis to establish signatures for distinguishing molecular subgroups of pediatric medulloblastoma.

Approach: Fifty newly diagnosed pediatric patients with medulloblastoma were enrolled in this study. Radiomic features were extracted from APT-related metrics to differentiate MB subgroups.

Results: APT MRI-based radiomic signatures exhibited favorable performance in identifying WNT, SHH, Group 3, and Group 4 subgroups with AUCs ≥ 0.91.

Impact: Our research findings demonstrate that amide proton transfer MRI-based radiomic analysis offers a noninvasive and cost-effective method to distinguish molecular subgroups and holds great potential in providing valuable clinical insights for the diagnosis of pediatric medulloblastoma patients.

Keywords: Structural Connectivity, Cancer

Motivation: Cognitive impairment following treatment of medulloblastoma has been associated with white matter structural changes and altered structural brain connectivity.

Goal(s): We hypothesized that decreased intensity therapy would reduce acute change in the working memory structural connectome.

Approach: Working memory structural connectomes were assessed relative to baseline after 15 Gy craniospinal irradiation (RT), after subsequent reduced-intensity chemotherapy, and during follow-up for 24 children treated for WNT-subtype (WNT) medulloblastoma.

Results: Changes after RT or chemotherapy showed small increases in connectivity strength in frontal striatal edges indicating little acute change. Follow-up revealed significant decreases in connectivity of the bilateral connections between caudate/thalamus.

Impact: Increased connectivity of frontal striatal edges after therapy and decreased connectivity of caudate/thalamus edges in follow-up for patients receiving reduced intensity therapy for WNT medulloblastoma may indicate a low incidence of acute changes.

Keywords: Cancer, Brain, pediatric brain tumor

Motivation: Pediatric brain tumors is the most common cancer among the pediatric population, and DWI-imaging offers a non-invasive method to assess tumor grade to guide appropriate treatments. 

Goal(s): The study investigates the feasibility of DISMANTLE, an integrated DWI approach for simultaneous assessment of tissue cellularity, vascularity, and heterogeneity, in differentiating high-grade and low-grade pediatric brain tumors.

Approach: Seventy pediatric patients with brain tumors, categorized into high-grade and low-grade, were scanned with DWI sequence. Images were analyzed using DISMANTLE and 3 comparison models.

Results: Removing the perfusion-related signal in DISMANTLE improved the accuracy and sensitivity of diffusion-related parameters in assessing pediatric brain tumor grades.

Impact: The study emphasizes the importance of appropriate signal characterization and fitting strategies for high b-value DWI in robust assessment of brain tumors. Future DWI modeling should consider segmentally fitting the diffusion and perfusion-related signals.

Keywords: Visualization, Cardiovascular, UTE, Access, Vasculature, Quality, CHD, Contrast, Chest, Abdomen, Diagnostic

Motivation: The motivation for this study is to propose an alternative and more efficient imaging protocol for vascular access assessment for complex congenital heart disease (CHD) cases

Goal(s): To determine if UTE imaging can provide a supplemental tool to conventional MR imaging for evaluating vascular access in the context of CHD.

Approach: Selection of 15 patients undergoing pre-operative assessment for complex CHD, including ferumoxytol administration, implement a 3D UTE sequence and a quality scoring scale.

Results: The study concludes that UTE imaging is a time-efficient method to visualize vascular anomalies, patency, occlusion, and access, and it can complement MRI planning for cardiovascular procedures.

Impact: Our study demonstrates that UTE imaging with ferumoxytol can provide high-quality vascular access imaging for patients with complex CHD. This offers an improved diagnostic tool for assessing vascular access as an important addition to the tools available for CHD evaluation.

Keywords: Cancer, Tumor, Hepatoblastoma; Metastasis; UTE

Motivation: UTE MR has demonstrated its potential for evaluating pulmonary lesions, which could be employed for assessing pulmonary metastasis from hepatoblastoma.

Goal(s): To investigate the diagnostic performance of UTE MR for detecting pulmonary nodules and thus diagnosing pulmonary metastasis in pediatric hepatoblastoma patients.

Approach: Lung UTE was assessed for its capability to detect nodules and for its diagnostic performance for pulmonary metastasis.

Results: UTE has a moderate diagnostic sensitivity for metastasis, while its specificity is high. When it comes to single pulmonary nodules, UTE has a moderate detection rate with a relatively high false positive detection rate.

Impact: UTE has a moderate diagnostic sensitivity for pulmonary metastasis, while its specificity is high. To make MR imaging a reliable one-stop assessment tool, higher resolution UTE imaging technology will be needed in the future.

Keywords: Body, Pediatric, LAVA-Flex, 3D FLEX

Motivation: Fat suppressed T1 images, such as LAVA-FLEX, are routinely used in pediatric abdominal imaging, but can suffer for SNR and IQ issues. 

Goal(s): Our goal was to validate application of 3D deep learning to 3D LAVA-FLEX via image quality assessment and noise characterization.

Approach: DL and conventionally reconstructed images were assessed by two radiologists and noise characteristics were evaluated by calculation of total variation and number of detected edges. 

Results: The radiologists preferred DL in a majority of cases (>80%), with noticeably lower noise and improved sharpness in DL images. 

Impact: The application of DL to routine pediatric 3D LAVA-FLEX imaging provides enhanced diagnostic quality, and has the potential to improve pediatric patient care.

Keywords: Cardiovascular, Cardiovascular, Noonan syndrome; non-syndromic hypertrophic cardiomyopathy; cardaic MRI; young children

Motivation: The high prevalence of cardiac involvement necessitates comprehensive cardiac exploration at diagnosis and during follow-up in NS, especially when NS was found to be a risk factor in children with HCM

Goal(s): Our study aimed to identify and assess the cardiac MRI features of NS in comparison with non-syndromic HCM in a cohort of young children

Approach: 10 young children genetically confirmed with NS and 10 children genetically confirmed with HCM were evaluated by cardiac MRI

Results: ROC curves documented the diagnostic performance of MRI features(LGE quantification, T1 mapping and strain analysis) in differentiating NS patients from HCM patients

Impact: We performed comprehensive evaluation of pediatric NS by comparison with non-syndromic HCM, and defined a vital role of cardiac MRI in NS. Comprehensive cardiac MRI findings will provide more insights into the rare hereditary cardiomyopathy for researchers and clinicians