Analysis of cortical dysplasias using b-tensor encoding diffusion MRI in an animal model
Presented During:
Thursday, June 27, 2024: 11:30 AM - 12:45 PM
COEX
Room:
Grand Ballroom 101-102
Poster No:
2365
Submission Type:
Abstract Submission
Authors:
Olimpia Ortega-Fimbres1, Alonso Ramírez-Manzanares2, Mónica López-Hidalgo1, Ricardo Rios-Carrillo1, Mirelta Regalado1, Hiram Luna-Munguía1, Luis Concha1
Institutions:
1Universidad Nacional Autónoma de México, Querétaro, Mexico, 2Centro de Investigación en Matemáticas, Guanajuato, Mexico
First Author:
Co-Author(s):
Introduction:
Focal cortical dysplasias (FCD) are cortical malformations that represent a major cause of drug-resistant focal epilepsy (Blümcke, 2011). Magnetic resonance images (MRI) are the main tool for their diagnosis and subsequent surgical intervention. However, despite clear histopathological changes, many FCDs lack macro-anatomical abnormalities, often going undetected (Guerrini & Barba, 2021). It is necessary to find better methods for their detection.
Diffusion weighted MRI (dMRI) is ideally suited to probe the architecture of tissue. However, in complex structures such as the cortex, conventional dMRI methods (e.g. DTI) are insufficient (Benjamini, 2021). Novel dMRI methods have been used to reflect regional and layer-level abnormalities in the cerebral cortex of rodents (Villaseñor et al., 2023) and humans (Lampinen 2020, Lorio 2020).
The b-tensor encoding method provides additional information contained in the dMRI signal and yields parameters more specific to the microstructure of tissue. Q-space trajectory imaging (QTI), an analysis technique for b-tensor encoding images, is used to derive micro fractional anisotropy (µFA) and orientation coherence (Cc), information that is not available with standard dMRI (Westin, 2016).
We show the ability of b-tensor dMRI to evaluate the characteristics of the microarchitecture of the cerebral cortex in a rodent model of cortical dysplasia, aiming to improve the detection of FCDs in clinical populations.
Diffusion weighted MRI (dMRI) is ideally suited to probe the architecture of tissue. However, in complex structures such as the cortex, conventional dMRI methods (e.g. DTI) are insufficient (Benjamini, 2021). Novel dMRI methods have been used to reflect regional and layer-level abnormalities in the cerebral cortex of rodents (Villaseñor et al., 2023) and humans (Lampinen 2020, Lorio 2020).
The b-tensor encoding method provides additional information contained in the dMRI signal and yields parameters more specific to the microstructure of tissue. Q-space trajectory imaging (QTI), an analysis technique for b-tensor encoding images, is used to derive micro fractional anisotropy (µFA) and orientation coherence (Cc), information that is not available with standard dMRI (Westin, 2016).
We show the ability of b-tensor dMRI to evaluate the characteristics of the microarchitecture of the cerebral cortex in a rodent model of cortical dysplasia, aiming to improve the detection of FCDs in clinical populations.
Methods:
Cortical abnormalities akin to those in FCD were created in Sprague-Dawley rats descended from females that were injected with either BCNU (20 mg/kg) or saline solution at the 15th day of pregnancy (Benardete & Kriegstein, 2002). The experimental animals (n=20/18 BCNU/control) were examined at 120 days after birth (P120).
Scanning was performed on a pre-clinical 7T scanner. b-tensor encoding dMRI were acquired using the sequence available in the Preclinical Neuro MRI repository (https://osf.io/ngu4a/) and consisted of 3 b-tensor shapes: linear, spherical and planar (Szczepankiewicz, 2019). Gradient waveforms were optimized using the NOW toolbox (https://github.com/jsjol/NOW), tuned (Lundell, 2019), and scaled in magnitude to achieve 4 b-values (200, 700, 1400 and 2000 s/mm²). Images were denoised with MP-PCA and corrected for geometric distortions. QTI was used to obtain fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), Cc and µFA. We used a curvilinear coordinate system to sample the dMRI parameters in the animal's cerebral cortex thus providing anatomical correspondence between animals. QTI metrics were obtained at each point, and t-tests were used to assess between-group differences.
After scanning, the animals were euthanized, the brains removed, and Nissl staining and immunofluorescence of myelin (MBP), glial cells (GFAP) and neurons (NeuN) were performed.
Scanning was performed on a pre-clinical 7T scanner. b-tensor encoding dMRI were acquired using the sequence available in the Preclinical Neuro MRI repository (https://osf.io/ngu4a/) and consisted of 3 b-tensor shapes: linear, spherical and planar (Szczepankiewicz, 2019). Gradient waveforms were optimized using the NOW toolbox (https://github.com/jsjol/NOW), tuned (Lundell, 2019), and scaled in magnitude to achieve 4 b-values (200, 700, 1400 and 2000 s/mm²). Images were denoised with MP-PCA and corrected for geometric distortions. QTI was used to obtain fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), Cc and µFA. We used a curvilinear coordinate system to sample the dMRI parameters in the animal's cerebral cortex thus providing anatomical correspondence between animals. QTI metrics were obtained at each point, and t-tests were used to assess between-group differences.
After scanning, the animals were euthanized, the brains removed, and Nissl staining and immunofluorescence of myelin (MBP), glial cells (GFAP) and neurons (NeuN) were performed.
Results:
The largest and most widespread between-group differences corresponded to µFA, which showed reductions in BCNU-treated animals throughout the mid-cortical layers. Other diffusion metrics showed abnormalities interspersed throughout the cortex at different depths.
Immunofluorescence analysis showed disorganized neuronal nuclei characteristic of cortical dysplasia. Moreover, myelin content was reduced in BCNU-treated animals, with overall less coherence in the spatial arrangement of myelinated fibers. Finally, experimental animals showed astrocytes that were increased in number and with enlarged processes.
Immunofluorescence analysis showed disorganized neuronal nuclei characteristic of cortical dysplasia. Moreover, myelin content was reduced in BCNU-treated animals, with overall less coherence in the spatial arrangement of myelinated fibers. Finally, experimental animals showed astrocytes that were increased in number and with enlarged processes.
·Figure 1
·Figure 2
Conclusions:
Advanced dMRI is able to detect abnormalities of the cortex in animals with histological features similar to those seen in FCD. µFA is highly sensitive to detect disorganized myeloarchitecture, which corresponds to alterations seen with immunofluorescence. Glial cells and neuronal dyslamination are also likely responsible for the identified diffusion alterations. b-tensor dMRI metrics are therefore promising for the detection of FCD in humans.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Cyto- and Myeloarchitecture 2
Novel Imaging Acquisition Methods:
Diffusion MRI 1
Keywords:
Cortex
Cortical Columns
Cortical Layers
Development
Epilepsy
MRI
1|2Indicates the priority used for review
Provide references using author date format
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