RPS 1912 - Imaging the growing brain

Author Block: J. Chuah, A. M. A. Manahan, S. Y. Chan, H. Pei, M. Fortier, M. Meaney, A. P. Tan; Singapore/SG
Purpose: Dysregulation of immune activation has been consistently shown in patients with mental health disorders. In this study, we mapped the trajectories of DNA-methylation based inflammation scores and examined how these trajectories relate to exposure to maternal depression, subsequent cognitive outcomes, and brain development at multiple levels.
Methods or Background: Inflammation scores were calculated for 293 children from DNA methylation data based on epigenome-wide association studies of serum C-reactive proteins at ages 9 and 48 months. We stratify these children into quartiles based on their inflammation scores at baseline and map the trajectories of inflammation scores for each quartile. Next, we examined if children with different inflammation score trajectories have different exposure to maternal depression, executive function performance, and brain changes evaluated using multimodal MRI at ages 4.5, 6.0, and 7.0 years.
Results or Findings: We observed a decreasing trend of our DNA-methylation based inflammation scores, primarily driven by children with higher levels of inflammation scores at baseline. Children with lower levels of inflammation scores at 9M and a slower decrease in inflammation scores between 9M and 48M were exposed to higher levels of maternal depressive symptoms and showed poorer executive function performance at ages 4.5 and 7. Children with different inflammation score trajectories exhibit significantly different brain structure and function, involving predominantly brain regions involved in executive function performance, emotion, and reward processing.
Conclusion: Children with lower baseline inflammation scores and slower rate of decrease across childhood are exposed to higher levels of maternal depression, possibly related to a blunted immune response from chronic stress exposure. This has a significant downstream impact on cognitive and brain development at multiple levels.
Limitations: Evaluation of executive function performance with questionnaires
Funding for this study: This research was supported by grants NMRC/TCR/004-NUS/2008 and NMRC/TCR/012-NUHS/2014 from the Singapore National Research Foundation (NRF) under the Translational and Clinical Research Flagship and grant OFLCG/MOH-000504 from the Open Fund Large Collaborative Grant Programmes and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore. In RIE2025, GUSTO is supported by funding from the NRF’s Human Health and Potential (HHP) Domain, under the Human Potential Programme. Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. MJM is supported by funding from the Hope for Depression Research Foundation, USA, the Toxic Stress Network of the JPB Foundation, USA, the Jacobs Foundation, Switzerland, and the NRF and A*STAR’s Human Potential Programme (H22P0M0001), Singapore. SYC is supported by funding from the NMRC Open Fund – Young Individual Research Grant (MOH-001149-00). EHT is supported by the NMRC Clinician-Scientist Award (CSA) (MOH-001415). APT is supported by funding from the NMRC Transition Award (MOH-001273-00) and A*STAR (Brain-Body Initiative, iGrants call ID #21718).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the National Healthcare Group Domain Specific Review Board (D/2009/021 and B/2014/00411) and the SingHealth Centralized Institutional Review Board (D/2018/2767 and A/2019/2406). All investigations were conducted according to the principles expressed in the Declaration of Helsinki. Written consent was obtained from all guardians on behalf of the enrolled children.

Author Block: M. Wang¹, H. Zhu², T. Huang³, J. Cheng², H. Jiang¹; ¹Wuxi/CN, ²Beijing/CN, ³Zhengzhou/CN
Purpose: To investigate the geometric microstructural changes in white matter in infants with periventricular white matter injury and spastic cerebral palsy (PWMI-SCP) and facilitate early prediction.
Methods or Background: PWMI is a high-risk factor for SCP. However, early identification of PWMI-SCP infants remains challenging. A novel mathematical framework, “Director Field Analysis” (DFA), reflects changes in the microstructural geometry of white matter and offers new insights into the pathological mechanisms of PWMI-SCP. DFA provides specific quantitative metrics, including splay, twist, bend, and total distortion index. Analysis of variance, correlation analysis, and receiver operating characteristics analysis were performed. Corrected p-values < 0.05 were considered significant.
Results or Findings: The PWMI-SCP group exhibited significantly elevated DFA metrics, primarily in the corpus callosum, posterior thalamic radiata, and corona radiata, comparing to the PWMI without SCP group, which were associated with enlarged lateral ventricles, reduced deep nuclear volumes and motor dysfunction. Mediation analysis indicated that increased geometric microstructure in the corpus callosum partially mediates the relationship between the lateral ventricles and motor function. A multi-parameter model based on DFA metrics can effectively predict PWMI-SCP with an AUC of 0.95.
Conclusion: Abnormal increases in white matter geometric microstructure in the sensorimotor circuit may be one of the neural substrates underlying the manifestation of SCP in PWMI infants. Monitoring fiber-orientational alterations may provide new insights into early prediction of PWMI-SCP.
Limitations: First, this study focused on infants aged 6−36 months; therefore, future research should investigate changes in white matter geometric microstructure in infants aged 0-6 months to improve the early diagnosis rate of PWMI-SCP. Additionally, biomolecular research is required to understand the interactions between brain morphology, tissue mechanics, and white matter geometric microstructure to elucidate the pathophysiological mechanisms of PWMI-SCP.
Funding for this study: This study was financially supported by grants from the STI 2030 - Major Project (Grant No. 2022ZD0209000); the Hong Kong global STEM scholar scheme; the internal fund of the Hong Kong Polytechnic University; the Wuxi Municipal Health Commission's 'Double Hundred' Medical Health Young Elite Talent Project (Grant No. BJ2023088) and the Wuxi Municipal Science and Technology Bureau's Medical and Health Tackling Project (Grant No. Y20232012); the Jiangsu Province Graduate Research Innovation Project (KYCX24_2647); National Natural Science Foundation of China (Grant No. 61971017, No. 82204933); Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning (Grant No. CNLZD2101).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study received institutional review board approval, and written informed consent was obtained from all participants.

Author Block: H. Ran, T. Zhang; Zunyi/CN
Purpose: Drug refractory left temporal lobe epilepsy (DRLTLE) often give rise to neuronal activity and cerebral vascular hemodynamics changes, which may result in neurovascular decoupling. However, neuroimaging evidence on neurovascular decoupling remains scarce, this study aimed to assess the manifestation of neurovascular coupling (NVC) in childhood DRLTLE using resting-state fMRI (rs-fMRI) and arterial spin labeling imaging (ASL).
Methods or Background: Based on the collected rs-fMRI and ASL imaging data, degree centrality (DC) and cerebral blood flow (CBF) were calculated respectively. Across voxel CBF-DC correlations used to evaluate the NVC within whole brain, and NVC of brain region was assessed by the CBF/DC ratio. We performed correlation analysis to evaluate the relationship between the variables. Finally, we explored classification problems between DRLTLE and healthy control (HC).
Results or Findings: Compared HC group, the DRLTLE children with higher across voxel CBF-DC correlations. The brain regions of abnormal CBF, DC, and CBF/DC ratio in predominantly in the default mode and the executive control network, the abnormally CBF, DC values in some brain regions were significantly correlated cognitive function. The classification model using CBF/DC ratio as features achieved the 72.8% accuracy, 0.764 area under the curve, 68.5% sensitivity, 87.5% specificity, the classification accuracy were higher than the model using CBF or DC feature.
Conclusion: The study reveals the cerebral blood perfusion, neuronal activity, global and regional NVC alteration in children with MRI-negative DRLTLE non-invasively, associated with lower cognitive performance. These findings indicating that NVC-based study can better integrate information of neuronal activity and cerebral hemodynamics, offering a new insight into the neuropathological mechanisms of DRLTLE, and NVC may help clinical classification for childhood DRLTLE.
Limitations: The sample size was relatively small and the potential impact of antiepileptic drugs could not totally eliminated.
Funding for this study: This study was supported by National Natural Science Foundation of China (Grant Nos .82171919) and Intelligent Medical Imaging Engineering Research Center of Guizhou Higher Education Institutions project (Grant No. Qianjiaoji [2023] 038)
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The ethic committee of Zunyi Medical University reviewed and granted ethical approval of this research (Ethical Batch Number: lunshen [2021] 1-080)

Author Block: P. D. Mika, J. Cydejko, B. Rowinski, D. Świętoń, E. Szurowska; Gdańsk/PL
Purpose: Important limitation of pediatric MRI imaging is requirement of general anesthesia (GA) in the youngest group of patients. Imaging in GA is not only stressful for children but also extends the time of the procedure. The solution is to use an incubator dedicated to work in a magnetic field. The MRI dedicated incubator allows a full spectrum of MRI imaging.
Analysis of examinations with the use of an MRI incubator performed at the Department of Radiology of the University Clinical Center in Gdansk .
Methods or Background: A retrospective evaluation of MRI examinations performed using an incubator carried out in the youngest group of patients. The study includes an analysis of the tests performed in terms of the child's age and the examined area.
The paper presents the benefits of using an MRI incubator. Sequences prepared specifically for test protocols in which the incubator is used are discussed Patients were tested in the "feed and sleep" protocol.
Results or Findings: Between 2020 and 2023, a total of 146 MRI examinations were performed. Most of the studies were brain scans without the administration of a contrast agent. Only in 1 case supplementary general sedation was necessary.
Conclusion: 1. The study showed a sharp increase in the number of studies using an incubator.
2. The incubator dedicated for MRI examinations allows to limit the amount of anesthesia in the youngest patients to 4 kg of body weight.
3. Increase in the cost of effectiveness of MRI examinations in the youngest group of patients due to the lack of anesthesia costs.
Limitations: Movement artifacts
Weight over 4kg
Implants not allowed for MRI
Funding for this study: No
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: No

Author Block: A. G. Gennari, L. Gaito, D. Cserpan, R. Kottke, R. Tuura O’Gorman, G. Ramantani; Zurich/CH
Purpose: In children with pharmacoresistant focal lesional epilepsy, lesion-associated brain perfusion changes captured by arterial spin labelling (ASL) are an emerging imaging tool improving lesion detection. However, their correlation with postsurgical seizure outcomes is still unexplored. This study aims to determine whether including ASL-derived perfusion changes in surgical planning is associated with favorable postsurgical seizure outcomes in children with focal cortical dysplasia (FCD) or low-grade epilepsy-associated tumors (LEAT).
Methods or Background: We retrospectively analyzed MRI scans from 18 children (median age at MRI: 4.8 years, IQR: 1.9–11.5) who underwent surgical resection for pharmacoresistant epilepsy and had at least 1 year of post-surgical follow-up. All patients received presurgical ASL imaging along with pre- and postsurgical structural MRI. Image postprocessing, including segmentation and coregistration, was used to qualitatively and quantitatively evaluate the completeness of resection of both the anatomical lesion and the ASL-detected perfusion changes. The DICE similarity index was adopted in quantitative analysis to grade the segmentations’ alignment. These findings were then correlated with seizure outcomes.
Results or Findings: Fourteen (78%) patients achieved complete seizure freedom. Qualitative analysis showed that complete resection of the ASL-detected perfusion changes significantly correlated with seizure freedom (p=0.009). Quantitative analysis indicated that higher degrees of alignment between perfusion and resection cavity segmentations, as measured by DICE score, were associated with seizure freedom (p=0.043), while lesion volume inclusion was not (p=0.44).
Conclusion: Including ASL perfusion imaging in the presurgical evaluation can help better define the epileptogenic zone, improving postsurgical seizure outcomes, and supporting it as a complementary tool in surgical planning for pharmacoresistant pediatric focal lesional epilepsy.
Limitations: Limitations:
- small sample size;
- focus on MRI-visible lesions only, limiting the generalizability to MRI-negative patients;
- manual segmentation, which may limit the reproducibility of our results.
Funding for this study: We thank the National Science Foundation (SNSF: 208184) (to G.R.), the Anna Mueller Grocholski Foundation, and the Theodor und Ida Herzog-Egli-Stiftung (to A.G.G.) for funding. The funders had no role in the design or analysis of the study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The collection and analysis of patient data were approved by and performed according to the guidelines and regulations of the local ethics committee (KEK-ZH PB-2024-00298). All parents gave written, informed general consent to reuse clinical data for research.

Author Block: R. Agarwal¹, U. Gupta², N. Jha²; ¹Bengaluru/IN, ²Ghaziabad/IN
Purpose: This study aims to assess MRI signal abnormalities in pediatric metabolic brain disorders, focusing on diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS). The goals are to identify specific imaging patterns, correlate them with clinical, biochemical, and genetic data, and enhance diagnostic accuracy for early intervention.
Methods or Background: Metabolic brain disorders in children are inherited conditions leading to progressive neurodegeneration, where early diagnosis is critical. This study evaluated 30 pediatric patients (aged 0-12 years) with suspected metabolic brain disorders using MRI, DWI, and proton MRS, along with biochemical and genetic testing. MRI findings were categorized based on the involvement of white matter, grey matter, or both.
Results or Findings: Of the 30 patients, 24 (80%) were diagnosed with metabolic brain disorders, predominantly in males (79.17%) and in the 0-3 years age group (62.5%). Common symptoms included regression of developmental milestones (70.83%) and seizures (58.33%). MRI showed white matter involvement in 10 cases, grey matter in 5, and both in 9. Diagnoses included X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Leigh disease, Wilson disease, glutaric aciduria type I, and neuronal ceroid lipofuscinosis. MRI findings included symmetrical T2 hyperintensities in 66.67%, diffusion restriction in 41.67%, and distinctive MRS peaks such as elevated N-acetylaspartate in Canavan disease and lactate in Leigh disease.
Conclusion: DWI and proton MRS are crucial for early diagnosis of pediatric metabolic brain disorders. Identifying characteristic imaging patterns enhances diagnostic precision and facilitates timely intervention, improving patient outcomes.
Limitations: The study's small sample size may limit the generalizability of the findings, and the cross-sectional design does not address disease progression over time. Future research should involve larger cohorts and longitudinal studies to validate these results and assess the long-term efficacy of imaging-based diagnostic methods.
Funding for this study: None
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Not required

Author Block: H. Ran, K. Huang, T. Zhang; Zunyi/CN
Purpose: Idiopathic generalized epilepsy(IGE) has been considered as a network disease, recurrent seizures may result in network reconfiguration and cognitive impairments. The dynamic changes in functional network in IGE children and the relationship with cognitive impairment and gene expression profiles needs to be explored.
Methods or Background: 26 IGE children and 35 healthy controls(HC) were recruited, the modular variability(MV) of constructed time-varying multi-layer network was calculated and compared between groups based on rs-fMRI. The correlation analysis was performed between MV and cognitive function scores and clinical variables. Allen Human Brain Atlas were used to identify gene sets associated with dynamic network remodeling in IGE. The associated biological processes, pathways were identified by gene enrichment tools.
Results or Findings: Compared to HC, IGE children demonstrated changed MV mainly located in the sensorimotor areas, salience/ventral attention, and default mode network, and at the sub-network level, children with IGE exhibited increased MV in the default mode network(p<0.05, FDR). MV changes in the left prefrontal, precuneus cortex were negatively correlated with the verbal IQ, full scale IQ and performance IQ scores, respectively(r=-0.400, -0.419, -0.408; p=0.042, 0.032, 0.038), while MV in the right orbitofrontal cortex was positively correlated with the verbal IQ and full scale IQ scores, respectively(r=0.488, 0.442; p=0.011, 0.023). Gene expression profiles was associated with dynamic network dysfunction in IGE(r=0.499, pperm < 0.05). Enrichment analysis indicated that the genes related to dynamic network reorganization were principally enriched in dendrite, axon, and nervous system development.
Conclusion: In IGE children, altered dynamic functional networks has been identified and correlated with cognitive function and gene expression, revealing the complex relationship between the dynamic changes of macroscopic modules and genetic pathological mechanisms in IGE patients.
Limitations: The sample size of this study was relative small.
Funding for this study: This study was supported by National Natural Science Foundation of China (Grant Nos .82171919) and Intelligent Medical Imaging Engineering Research Center of Guizhou Higher Education Institutions project (Grant No. Qianjiaoji [2023] 038)
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Ethics approval of this research was granted by the Ethic Committee of the Affiliated Hospital of Zunyi Medical University[KLL-2021-347]