Morphometry Longitudinal Study until Adolescence of Brain Growth after early lesion : Sex matters !
Poster No:
395
Submission Type:
Abstract Submission
Authors:
Pierre-Yves POSTIC1, Yann Leprince2, Soraya Brosset1, Inès Ben Abdallah1, Stephane Chabrier3, Mickael Dinomais4, Edouard Duchesnay5, Lucie HERTZ-PANNIER1
Institutions:
1CEA Saclay NeuroSpin/UNIACT/InDEV, U1141/Inserm, Gif-sur-Yvette, Ile-de-France, 2CEA Saclay Neurospin/UNIACT, Université Paris-Saclay, F-91191, Gif-sur-Yvette, Ile-de-France, 3CHU Saint-Etienne, Saint-Etienne, Auvergne-Rhône-Alpes, 4CHU Angers, Angers, Pays de la Loire, 5CEA Saclay NeuroSpin/BAOBAB/GAIA/SIGNATURE, Université Paris-Saclay, F-91191, Gif-sur-Yvette, Ile-de-France
First Author:
Co-Author(s):
Yann Leprince
CEA Saclay Neurospin/UNIACT, Université Paris-Saclay, F-91191
Gif-sur-Yvette, Ile-de-France
CEA Saclay Neurospin/UNIACT, Université Paris-Saclay, F-91191
Gif-sur-Yvette, Ile-de-France
Edouard Duchesnay
CEA Saclay NeuroSpin/BAOBAB/GAIA/SIGNATURE, Université Paris-Saclay, F-91191
Gif-sur-Yvette, Ile-de-France
CEA Saclay NeuroSpin/BAOBAB/GAIA/SIGNATURE, Université Paris-Saclay, F-91191
Gif-sur-Yvette, Ile-de-France
Introduction:
While plasticity of the immature brain is deemed critical for optimized neurodevelopmental outcome, early brain lesions may result in enduring neurocognitive impairments [1], suggesting global dysfunction. However, the varied outcomes across individuals remain insufficiently elucidated.
Neonatal ischemic stroke (NAIS) serves as a model for exploring the pivotal role of post-lesional plasticity in the immature brain. Among other variables, males represent 2/3 of NAIS cases, suggesting a potential sex-related effect on long-term neuroplasticity after early brain lesions.
We performed a longitudinal morphometric study until adolescence of the growth dynamics of brain compartments within both ipsilesional and contralesional hemispheres in patients (P) with NAIS compared to controls (C), with a focus on sex differences.
Neonatal ischemic stroke (NAIS) serves as a model for exploring the pivotal role of post-lesional plasticity in the immature brain. Among other variables, males represent 2/3 of NAIS cases, suggesting a potential sex-related effect on long-term neuroplasticity after early brain lesions.
We performed a longitudinal morphometric study until adolescence of the growth dynamics of brain compartments within both ipsilesional and contralesional hemispheres in patients (P) with NAIS compared to controls (C), with a focus on sex differences.
Methods:
The follow-up of the French AVCnn[2] cohort of neonates with unilateral NAIS involved clinical assessments and multimodal MRI imaging at ages 7 and 16.
- P : age 7y , N = 39 (23 M, 16 F) ; age 16y, N = 29 (18 M, 11 F). No M/F significant differences of lesion severity nor side (2/3 left).
- C : age 7y, N = 35 (17 M ,18 F); age 16y, N = 31 (16 M, 15 F)
- 22 P and 16 C assessed at both ages
3T MRI morphometry : 3DTI, 1mm and 0.9mm isotropic resolution at age 7 and 16, respectively
Volumes were computed in Regions of interest (ROIs) in both ipsi- (ILH) and contra-lesional (CLH) hemispheres, and compared to C. In the ILH, ROIs were restricted to non-lesioned areas, using a combination of clinical and imaging criteria, with careful QC at each step.
- Hemispheric white matter (WM), cortical grey matter (CGM) and total hemisphere (H) (CAT12, Hammers atlas [3,4])
- Lobar CGM (CerebrA atlas [5] registered from MNI to native space with ANTs[6])
- Sub-cortical GM structures (Vol2Brain [7], manually corrected)
A finer investigation of the CLH involved regional CGM volumes and thickness. (CAT12, Desikan-Killiany atlas [8]).
Metrics were analysed using a Generalized Linear Mixed Model (GLMM), with Age, Sex, Status (P vs. C), side and lesion severity, as co-variables. Post-hoc tests further compared P with C by age and sex.
- P : age 7y , N = 39 (23 M, 16 F) ; age 16y, N = 29 (18 M, 11 F). No M/F significant differences of lesion severity nor side (2/3 left).
- C : age 7y, N = 35 (17 M ,18 F); age 16y, N = 31 (16 M, 15 F)
- 22 P and 16 C assessed at both ages
3T MRI morphometry : 3DTI, 1mm and 0.9mm isotropic resolution at age 7 and 16, respectively
Volumes were computed in Regions of interest (ROIs) in both ipsi- (ILH) and contra-lesional (CLH) hemispheres, and compared to C. In the ILH, ROIs were restricted to non-lesioned areas, using a combination of clinical and imaging criteria, with careful QC at each step.
- Hemispheric white matter (WM), cortical grey matter (CGM) and total hemisphere (H) (CAT12, Hammers atlas [3,4])
- Lobar CGM (CerebrA atlas [5] registered from MNI to native space with ANTs[6])
- Sub-cortical GM structures (Vol2Brain [7], manually corrected)
A finer investigation of the CLH involved regional CGM volumes and thickness. (CAT12, Desikan-Killiany atlas [8]).
Metrics were analysed using a Generalized Linear Mixed Model (GLMM), with Age, Sex, Status (P vs. C), side and lesion severity, as co-variables. Post-hoc tests further compared P with C by age and sex.
Results:
Models Factors (Fig1) showed expected developmental trajectories of most volumes in both groups:
- Smaller volumes in females than in males at both ages, in P and C
- CGM decreases, WM increases between 7 and 16
In patients, growth trajectories differed between ILH and CLH, according to lesion severity and sex. Lesion side had no impact on the hemisphere/lobar results, but showed varied impacts on finer assessment with the DK40 atlas (not shown here).
ILH volumes were consistently 15% lower on average in patients than in controls, irrespective of age or sex (Fig2).
Lesion severity impacted most ILH volumes, but not CLH ones (except caudate nucleus).
In the CLH, male patients exhibited significantly lower volumes than controls, in all regions except the occipital lobe (-8 to -12%, significant). By contrast, female patients volumes were 2 to 5% larger than controls (not significant, except for the hippocampus and pallidum at age 16). These effects were similar at age 7 and 16
- Smaller volumes in females than in males at both ages, in P and C
- CGM decreases, WM increases between 7 and 16
In patients, growth trajectories differed between ILH and CLH, according to lesion severity and sex. Lesion side had no impact on the hemisphere/lobar results, but showed varied impacts on finer assessment with the DK40 atlas (not shown here).
ILH volumes were consistently 15% lower on average in patients than in controls, irrespective of age or sex (Fig2).
Lesion severity impacted most ILH volumes, but not CLH ones (except caudate nucleus).
In the CLH, male patients exhibited significantly lower volumes than controls, in all regions except the occipital lobe (-8 to -12%, significant). By contrast, female patients volumes were 2 to 5% larger than controls (not significant, except for the hippocampus and pallidum at age 16). These effects were similar at age 7 and 16
Conclusions:
Results show that the long-term impact of NAIS on ILH growth is mostly contingent on lesion severity. Conversely, the CLH is not affected by lesion severity, but shows sex-related differential effects, being more profoundly impacted in males, with females deviating minimally from the typical trajectory. This pattern is visible from childhood on, and puberty seems to exert minimal influence.
Overall, these results are in line with the known perinatal vulnerability of male brains and their higher susceptibility to neurodevelopmental disorders. Preliminary clinical analyses suggest that sex-related variance of neurocognitive outcomes remains modest in comparison to other determinants, thus is often overlooked. Our results advocate for systematic differential analysis of sex effects when studying neurodevelopmental conditions.
Overall, these results are in line with the known perinatal vulnerability of male brains and their higher susceptibility to neurodevelopmental disorders. Preliminary clinical analyses suggest that sex-related variance of neurocognitive outcomes remains modest in comparison to other determinants, thus is often overlooked. Our results advocate for systematic differential analysis of sex effects when studying neurodevelopmental conditions.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Lifespan Development:
Early life, Adolescence, Aging 2
Modeling and Analysis Methods:
Segmentation and Parcellation
Keywords:
Development
Morphometrics
Pediatric Disorders
Plasticity
Sexual Dimorphism
Spatial Normalization
STRUCTURAL MRI
Other - Longitudinal study
1|2Indicates the priority used for review
Provide references using author date format
[2] Chabrier, S., Peyric, E., Drutel, L., Deron, J., Kossorotoff, M., Dinomais, M., ... & Vuillerot, C. (2016). Multimodal outcome at 7 years of age after neonatal arterial ischemic stroke. The Journal of pediatrics, 172, 156-161
[3] Gaser, C., Dahnke, R., Thompson, P. M., Kurth, F., Luders, E., & Alzheimer’s Disease Neuroimaging Initiative. (2022). CAT–A computational anatomy toolbox for the analysis of structural MRI data. biorxiv, 2022-06
[4] Hammers, A., Allom, R., Koepp, M. J., Free, S. L., Myers, R., Lemieux, L., ... & Duncan, J. S. (2003). Three‐dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Human brain mapping, 19(4), 224-247
[5] Manera, A. L., Dadar, M., Fonov, V., & Collins, D. L. (2020). CerebrA, registration and manual label correction of Mindboggle-101 atlas for MNI-ICBM152 template. Scientific Data, 7(1), 237
[6] Avants, B. B., Tustison, N., & Song, G. (2009). Advanced normalization tools (ANTS). Insight j, 2(365), 1-35
[7] Manjón, J. V., Romero, J. E., Vivo-Hernando, R., Rubio, G., Aparici, F., de la Iglesia-Vaya, M., & Coupé, P. (2022). vol2Brain: A new online Pipeline for whole Brain MRI analysis. Frontiers in Neuroinformatics, 16, 862805
[8] Desikan, R. S., Ségonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., ... & Killiany, R. J. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage, 31(3), 968-980