Fatemeh Fadaie - Academia.edu (original) (raw)

Papers by Fatemeh Fadaie

Research paper thumbnail of Temporal lobe epilepsy

Neurology, Apr 19, 2019

Objective To assess whether hippocampal sclerosis (HS) severity is mirrored at the level of large... more Objective To assess whether hippocampal sclerosis (HS) severity is mirrored at the level of large-scale networks. Methods We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 temporal lobe epilepsy (TLE) patients with histopathologic diagnosis of HS (n = 25; TLE-HS) and isolated gliosis (n = 19; TLE-G) and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm that simulates functional dynamics from structural network data. Results Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from gray matter atrophy. Conclusions Severe HS is associated with marked remodeling of connectome topology and structurally governed functional dynamics in TLE, as opposed to isolated gliosis, which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales.

Research paper thumbnail of MRI-Derived Modeling of Disease Progression Patterns in Patients With Temporal Lobe Epilepsy

Research paper thumbnail of A Neuroimaging Network-Level Approach to Drug-Resistant Epilepsy

Cambridge University Press eBooks, Dec 31, 2022

Research paper thumbnail of Orginal Article Comparative Neurocognitive Functions of Schizophrenics and Temporal Lobe Ep- ileptic Patients

Introduction: Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has be... more Introduction: Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has been introduced long term ago. Similar neuropathology leads to the analogous clinical features like neuropsychological features as an example. The aim of this study was to examine this hypothesis by the means of comparing neuropsychological functions in these two patient groups. Methods: Present study consisted of 28 DSM_IV_TR schizophrenics and 29 patients with temporal lobe epilepsy recruited from Roozbeh, Razi and khatamolanbia hospital in Tehran by convenient sampling method. SCID in schizophrenic group and EEG, MRI in epileptic patients were taken in regard to diagnostic determination. Neuropsychological tests were taken later. Package of neuropsychological tests consisted of Modified Wisconsin Card Sorting Test, Stroop Color- Word Test, Logic Memory, Visual Reproduction and Digit Span subscales of Wechsler Memory Scale- Revised and Block Design, Vocabulary and Symbol Digit subscales ...

Research paper thumbnail of Unsupervised machine learning reveals lesional variability in focal cortical dysplasia at mesoscopic scale

NeuroImage: Clinical

Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a ... more Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a prevalent cause of surgically amenable epilepsy. While cellular and molecular biology data suggest that FCD lesional characteristics lie along a spectrum, this notion remains to be verified in vivo. We tested the hypothesis that machine learning applied to MRI captures FCD lesional variability at a mesoscopic scale. Methods: We studied 46 patients with histologically verified FCD Type II and 35 age-and sex-matched healthy controls. We applied consensus clustering, an unsupervised learning technique that identifies stable clusters based on bootstrap-aggregation, to 3 T multicontrast MRI (T1-weighted MRI and FLAIR) features of FCD normalized with respect to distributions in controls. Results: Lesions were parcellated into four classes with distinct structural profiles variably expressed within and across patients: Class-1 with isolated white matter (WM) damage; Class-2 combining grey matter (GM) and WM alterations; Class-3 with isolated GM damage; Class-4 with GM-WM interface anomalies. Class membership was replicated in two independent datasets. Classes with GM anomalies impacted local function (resting-state fMRI derived ALFF), while those with abnormal WM affected large-scale connectivity (assessed by degree centrality). Overall, MRI classes reflected typical histopathological FCD characteristics: Class-1 was associated with severe WM gliosis and interface blurring, Class-2 with severe GM dyslamination and moderate WM gliosis, Class-3 with moderate GM gliosis, Class-4 with mild interface blurring. A detection algorithm trained on class-informed data outperformed a class-naïve paradigm. Significance: Machine learning applied to widely available MRI contrasts uncovers FCD Type II variability at a mesoscopic scale and identifies tissue classes with distinct structural dimensions, functional and histopathological profiles. Integrating in vivo staging of FCD traits with automated lesion detection is likely to inform the development of novel personalized treatments.

Research paper thumbnail of Data from: Temporal lobe epilepsy: hippocampal pathology modulates white matter connectome topology and controllability

OBJECTIVE. To assess whether HS severity is mirrored at the level of large-scale networks. METHOD... more OBJECTIVE. To assess whether HS severity is mirrored at the level of large-scale networks. METHODS. We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 TLE patients with histopathological diagnosis of HS (n=25; TLE-HS) and isolated gliosis (n=19; TLE-G), and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm which simulates functional dynamics from structural network data. RESULTS. Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from grey matter atrophy. CONCLUSIONS. Severe HS is associated with marked remodeling of connectome topology and structurally-governed functional dynamics in TLE, as opposed to isolated gliosis which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales

Research paper thumbnail of Atypical functional connectome hierarchy impacts cognition in temporal lobe epilepsy

Epilepsia, 2021

Drug‐resistant temporal lobe epilepsy (TLE) is typically associated with hippocampal pathology. H... more Drug‐resistant temporal lobe epilepsy (TLE) is typically associated with hippocampal pathology. However, widespread network alterations are increasingly recognized and suggested to perturb cognitive function in multiple domains. Here we tested (1) whether TLE shows atypical cortical hierarchical organization, differentiating sensory and higher order systems; and (2) whether atypical hierarchy predicts cognitive impairment.

Research paper thumbnail of Automated Detection of Epileptogenic Cortical Malformations Using Multimodal MRI

Deep Learning in Medical Image Analysis and Multimodal Learning for Clinical Decision Support, 2017

Focal cortical dysplasia (FCD), a malformation of cortical development, is a frequent cause of dr... more Focal cortical dysplasia (FCD), a malformation of cortical development, is a frequent cause of drug-resistant epilepsy. This surgically-amenable lesion is histologically characterized by cortical dyslamination, dysmorphic neurons, and balloon cells, which may extend into the immediate subcortical white matter. On MRI, FCD is typically associated with cortical thickening, blurring of the cortical boundary, and intensity anomalies. Notably, even histologically-verified FCD may not be clearly visible on preoperative MRI. We propose a novel FCD detection algorithm, which aggregates surface-based descriptors of morphology and intensity derived from T1-weighted (T1w) MRI, T2-weighted fluid attenuation inversion recovery (FLAIR) MRI, and FLAIR/T1w ratio images. Features were systematically sampled at multiple intracortical/subcortical levels and fed into a two-stage classifier for automated lesion detection based on ensemble learning. Using 5-fold cross-validation, we evaluated the approach in 41 patients with histologically-verified FCD and 38 age-and sex-matched healthy controls. Our approach showed excellent sensitivity (83%, 34/41 lesions detected) and specificity (92%, no findings in 35/38 controls), suggesting benefits for presurgical diagnostics.

Research paper thumbnail of Deep Convolutional Networks for Automated Detection of Epileptogenic Brain Malformations

Focal cortical dysplasia (FCD) is a prevalent surgically-amenable epileptogenic malformation of c... more Focal cortical dysplasia (FCD) is a prevalent surgically-amenable epileptogenic malformation of cortical development. On MRI, FCD typically presents with cortical thickening, hyperintensity, and blurring of the gray-white matter interface. These changes may be visible to the naked eye, or subtle and be easily overlooked. Despite advances in MRI analytics, current surface-based algorithms fail to detect FCD in 50% of cases. Moreover, arduous data pre-processing and specialized expertise preclude widespread use. Here we propose a novel algorithm that harnesses feature-learning capability of convolutional neural networks (CNNs) with minimal data pre-processing. Our classifier, trained on a patch-based augmented dataset derived from patients with histologically-validated FCD operates directly on MRI voxels to distinguish the lesion from healthy tissue. The algorithm was trained and cross-validated on multimodal MRI data from a single site (S1) and evaluated on independent data from S1 a...

Research paper thumbnail of Decomposing MRI phenotypic heterogeneity in epilepsy: a step towards personalized classification

Brain, 2021

In drug-resistant temporal lobe epilepsy, precise predictions of drug response, surgical outcome ... more In drug-resistant temporal lobe epilepsy, precise predictions of drug response, surgical outcome and cognitive dysfunction at an individual level remain challenging. A possible explanation may lie in the dominant ‘one-size-fits-all’ group-level analytical approaches that does not allow parsing interindividual variations along the disease spectrum. Conversely, analysing inter-patient heterogeneity is increasingly recognized as a step towards person-centred care. Here, we used unsupervised machine learning to estimate latent relations (or disease factors) from 3 T multimodal MRI features [cortical thickness, hippocampal volume, fluid-attenuated inversion recovery (FLAIR), T1/FLAIR, diffusion parameters] representing whole-brain patterns of structural pathology in 82 patients with temporal lobe epilepsy. We assessed the specificity of our approach against age- and sex-matched healthy individuals and a cohort of frontal lobe epilepsy patients with histologically verified focal cortical ...

Research paper thumbnail of MRI-Based Machine Learning Prediction Framework to Lateralize Hippocampal Sclerosis in Patients With Temporal Lobe Epilepsy

Neurology, 2021

Background and ObjectivesMRI fails to reveal hippocampal pathology in 30% to 50% of temporal lobe... more Background and ObjectivesMRI fails to reveal hippocampal pathology in 30% to 50% of temporal lobe epilepsy (TLE) surgical candidates. To address this clinical challenge, we developed an automated MRI-based classifier that lateralizes the side of covert hippocampal pathology in TLE.MethodsWe trained a surface-based linear discriminant classifier that uses T1-weighted (morphology) and T2-weighted and fluid-attenuated inversion recovery (FLAIR)/T1 (intensity) features. The classifier was trained on 60 patients with TLE (mean age 35.6 years, 58% female) with histologically verified hippocampal sclerosis (HS). Images were deemed to be MRI negative in 42% of cases on the basis of neuroradiologic reading (40% based on hippocampal volumetry). The predictive model automatically labeled patients as having left or right TLE. Lateralization accuracy was compared to electroclinical data, including side of surgery. Accuracy of the classifier was further assessed in 2 independent TLE cohorts with ...

Research paper thumbnail of Whole-brain multimodal MRI phenotyping of periventricular nodular heterotopia

Neurology, 2020

ObjectiveTo test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and ... more ObjectiveTo test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and function of cortical areas overlying the heterotopic gray matter are preferentially affected.MethodsWe studied a group of 40 patients with PVNH and normal-appearing cortex and compared their quantitative MRI markers of brain development, structure, and function to those of 43 age- and sex-matched healthy controls. Inspired by models of neocortical development suggesting that neuronal migration follows a curvilinear path to preserve topologic correspondence between the outer ventricular zone and the cortical surface, we computationally defined the overlying cortex using the Laplace equation and generated synthetic streamlines that link the ventricles, where nodules are located, and the neocortex.ResultsWe found multilobar cortical thickening encompassing prefrontal, latero-basal temporal, and temporoparietal cortices largely corresponding with the PVNH group-averaged map of the overlying ...

Research paper thumbnail of Comparative Neurocognitive Functions of Schizophrenics and temporal lobe epileptic Patients

Introduction : Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has b... more Introduction : Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has been introduced long term ago. Similar neuropathology leads to the analogous clinical features like neuropsychological features as an example. The aim of this study was to examine this hypothesis by the means of comparing neuropsychological functions in these two patient groups. Method : Present study consisted of 28 DSM_IV_TR schizophrenics and 29 patients with temporal lobe epilepsy recruited from Roozbeh, Razi and khatamolanbia hospital in Tehran by convenient sampling method. SCID in schizophrenic group and EEG, MRI in epileptic patients were taken in regard to diagnostic determination. Neuropsychological tests were taken later. Package of neuropsychological tests consisted of Modified Wisconsin Card Sorting Test, Stroop Color- Word Test, Logic Memory, Visual Reproduction and Digit Span subscales of Wechsler Memory Scale- Revised and Block Design, Vocabulary and Symbol Digit subscales...

Research paper thumbnail of Altered communication dynamics reflect cognitive deficits in temporal lobe epilepsy

Epilepsia, 2021

Although temporal lobe epilepsy (TLE) is recognized as a system‐level disorder, little work has i... more Although temporal lobe epilepsy (TLE) is recognized as a system‐level disorder, little work has investigated pathoconnectomics from a dynamic perspective. By leveraging computational simulations that quantify patterns of information flow across the connectome, we tested the hypothesis that network communication is abnormal in this condition, studied the interplay between hippocampal‐ and network‐level disease effects, and assessed associations with cognition.

Research paper thumbnail of 1H-MRS metabolite’s ratios show temporal alternation in temporal lobe seizure: Comparison between interictal and postictal phases

Epilepsy Research, 2016

PURPOSES To determine 1H-MRSI metabolites changes in interictal and postictal phases of patients ... more PURPOSES To determine 1H-MRSI metabolites changes in interictal and postictal phases of patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis and lateralization of seizure foci. MATERIALS AND METHODS MR spectroscopic imaging was performed in 5 adult patients with refractory temporal lobe epilepsy interictally and immediately after the seizure and in 4 adult control subjects. All patients underwent MR imaging and VideoEEG Monitoring. RESULTS The results showed statistically significant decreases in N-acetylaspartate/Creatine, N-acetylaspartate/Choline and N-acetylaspartate/(creatine+choline) immediately after ictus in ipsilateral hippocampus as compared with control data and contralateral hippocampus of patients while no statistically significant difference was presented in interictal phase. CONCLUSION The present study clearly indicates 1H-MRS abnormalities following an ictus of temporal lobe epilepsy with metabolite recovery in interictal phase. This finding suggests postictal 1H-MRS as a possible useful tool to assist in lateralizing and localizing of seizure foci in epileptic patients with structural lesions.

Research paper thumbnail of The Use of Proton MR Spectroscopy in Epilepsy: A Methodological Review

Frontiers in Biomedical Technologies

Magnetic Resonance Spectroscopy (MRS) has at least two major roles in the evaluation of epileptic... more Magnetic Resonance Spectroscopy (MRS) has at least two major roles in the evaluation of epileptic patients. First, MRS can help to understand the interaction between seizures and metabolic function. Thus, MRS is particularly interesting for basic science studies of seizures and epilepsy. Second, MRS can explain the nature of seizure control and/or provide localization information by measuring metabolic changes. So MRS can be used as a powerful complementary technique to structural MRI for diagnosis and assessment of response to therapy, and measurement of disease progression. The aim of this paper is to review the methodological aspects of 1H-MRS publications between 1994 to 2016, which utilized 1H-MRS in lateralizing the epileptogenic zone in lesional and non-lesional Temporal Lobe Epilepsy (TLE), Extra-Temporal Lobe Epilepsy (ETLE), and generalized epileptic patients to help the spectroscopist, magnetic resonance imaging technologists, and radiologists to improve the overall diagn...

Research paper thumbnail of Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study

NeuroImage, Jan 3, 2017

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map wide... more The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effect...

Research paper thumbnail of Developmental MRI markers cosegregate juvenile patients with myoclonic epilepsy and their healthy siblings

Neurology

ObjectiveMRI studies of genetic generalized epilepsies have mainly described group-level changes ... more ObjectiveMRI studies of genetic generalized epilepsies have mainly described group-level changes between patients and healthy controls. To determine the endophenotypic potential of structural MRI in juvenile myoclonic epilepsy (JME), we examined MRI-based cortical morphologic markers in patients and their healthy siblings.MethodsIn this prospective, cross-sectional study, we obtained 3T MRI in patients with JME, siblings, and controls. We mapped sulco-gyral complexity and surface area, morphologic markers of brain development, and cortical thickness. Furthermore, we calculated mean geodesic distance, a surrogate marker of cortico-cortical connectivity.ResultsCompared to controls, patients and siblings showed increased folding complexity and surface area in prefrontal and cingulate cortices. In these regions, they also displayed abnormally increased geodesic distance, suggesting network isolation and decreased efficiency, with strongest effects for limbic, fronto-parietal, and dorsal...

Research paper thumbnail of Cardiac arrest associated with epileptic seizures: A case report with simultaneous EEG and ECG

Epilepsy Behavior Case Reports, 2014

Ictal asystole is a rare, probably underestimated manifestation of epileptic seizures whose patho... more Ictal asystole is a rare, probably underestimated manifestation of epileptic seizures whose pathophysiology is still debated. This report describes two patients who had cardiac asystole at the end of their seizure. The first patient was a 13-year-old boy with complex partial seizures.. His MRI showed symmetrical signal abnormality in the bilateral parietooccipital lobe accompanied by mild gliosis and volume loss. During a 3-day long-term video-EEG monitoring, he had cardiac arrest at the end of one of his seizures that was secondarily generalized. The second one was a 42-year-old veteran with penetrating head trauma in the left frontal lobe due to shell injury. During long-term video-EEG monitoring, he had one generalized tonic-clonic seizure accompanied by bradycardia and cardiac asystole. Asystoles could have a role in the incidence of sudden unexpected death in epilepsy (SUDEP), meaning that the presence of ictal bradycardia is a risk factor for SUDEP. In cases of epileptic cardiac dysrhythmia, prolonged simultaneous EEG/ECG monitoring may be required. Cardiological investigation should be included in epilepsy management.

Research paper thumbnail of Temporal lobe epilepsy

Neurology, Apr 19, 2019

Objective To assess whether hippocampal sclerosis (HS) severity is mirrored at the level of large... more Objective To assess whether hippocampal sclerosis (HS) severity is mirrored at the level of large-scale networks. Methods We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 temporal lobe epilepsy (TLE) patients with histopathologic diagnosis of HS (n = 25; TLE-HS) and isolated gliosis (n = 19; TLE-G) and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm that simulates functional dynamics from structural network data. Results Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from gray matter atrophy. Conclusions Severe HS is associated with marked remodeling of connectome topology and structurally governed functional dynamics in TLE, as opposed to isolated gliosis, which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales.

Research paper thumbnail of MRI-Derived Modeling of Disease Progression Patterns in Patients With Temporal Lobe Epilepsy

Research paper thumbnail of A Neuroimaging Network-Level Approach to Drug-Resistant Epilepsy

Cambridge University Press eBooks, Dec 31, 2022

Research paper thumbnail of Orginal Article Comparative Neurocognitive Functions of Schizophrenics and Temporal Lobe Ep- ileptic Patients

Introduction: Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has be... more Introduction: Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has been introduced long term ago. Similar neuropathology leads to the analogous clinical features like neuropsychological features as an example. The aim of this study was to examine this hypothesis by the means of comparing neuropsychological functions in these two patient groups. Methods: Present study consisted of 28 DSM_IV_TR schizophrenics and 29 patients with temporal lobe epilepsy recruited from Roozbeh, Razi and khatamolanbia hospital in Tehran by convenient sampling method. SCID in schizophrenic group and EEG, MRI in epileptic patients were taken in regard to diagnostic determination. Neuropsychological tests were taken later. Package of neuropsychological tests consisted of Modified Wisconsin Card Sorting Test, Stroop Color- Word Test, Logic Memory, Visual Reproduction and Digit Span subscales of Wechsler Memory Scale- Revised and Block Design, Vocabulary and Symbol Digit subscales ...

Research paper thumbnail of Unsupervised machine learning reveals lesional variability in focal cortical dysplasia at mesoscopic scale

NeuroImage: Clinical

Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a ... more Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a prevalent cause of surgically amenable epilepsy. While cellular and molecular biology data suggest that FCD lesional characteristics lie along a spectrum, this notion remains to be verified in vivo. We tested the hypothesis that machine learning applied to MRI captures FCD lesional variability at a mesoscopic scale. Methods: We studied 46 patients with histologically verified FCD Type II and 35 age-and sex-matched healthy controls. We applied consensus clustering, an unsupervised learning technique that identifies stable clusters based on bootstrap-aggregation, to 3 T multicontrast MRI (T1-weighted MRI and FLAIR) features of FCD normalized with respect to distributions in controls. Results: Lesions were parcellated into four classes with distinct structural profiles variably expressed within and across patients: Class-1 with isolated white matter (WM) damage; Class-2 combining grey matter (GM) and WM alterations; Class-3 with isolated GM damage; Class-4 with GM-WM interface anomalies. Class membership was replicated in two independent datasets. Classes with GM anomalies impacted local function (resting-state fMRI derived ALFF), while those with abnormal WM affected large-scale connectivity (assessed by degree centrality). Overall, MRI classes reflected typical histopathological FCD characteristics: Class-1 was associated with severe WM gliosis and interface blurring, Class-2 with severe GM dyslamination and moderate WM gliosis, Class-3 with moderate GM gliosis, Class-4 with mild interface blurring. A detection algorithm trained on class-informed data outperformed a class-naïve paradigm. Significance: Machine learning applied to widely available MRI contrasts uncovers FCD Type II variability at a mesoscopic scale and identifies tissue classes with distinct structural dimensions, functional and histopathological profiles. Integrating in vivo staging of FCD traits with automated lesion detection is likely to inform the development of novel personalized treatments.

Research paper thumbnail of Data from: Temporal lobe epilepsy: hippocampal pathology modulates white matter connectome topology and controllability

OBJECTIVE. To assess whether HS severity is mirrored at the level of large-scale networks. METHOD... more OBJECTIVE. To assess whether HS severity is mirrored at the level of large-scale networks. METHODS. We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 TLE patients with histopathological diagnosis of HS (n=25; TLE-HS) and isolated gliosis (n=19; TLE-G), and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm which simulates functional dynamics from structural network data. RESULTS. Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from grey matter atrophy. CONCLUSIONS. Severe HS is associated with marked remodeling of connectome topology and structurally-governed functional dynamics in TLE, as opposed to isolated gliosis which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales

Research paper thumbnail of Atypical functional connectome hierarchy impacts cognition in temporal lobe epilepsy

Epilepsia, 2021

Drug‐resistant temporal lobe epilepsy (TLE) is typically associated with hippocampal pathology. H... more Drug‐resistant temporal lobe epilepsy (TLE) is typically associated with hippocampal pathology. However, widespread network alterations are increasingly recognized and suggested to perturb cognitive function in multiple domains. Here we tested (1) whether TLE shows atypical cortical hierarchical organization, differentiating sensory and higher order systems; and (2) whether atypical hierarchy predicts cognitive impairment.

Research paper thumbnail of Automated Detection of Epileptogenic Cortical Malformations Using Multimodal MRI

Deep Learning in Medical Image Analysis and Multimodal Learning for Clinical Decision Support, 2017

Focal cortical dysplasia (FCD), a malformation of cortical development, is a frequent cause of dr... more Focal cortical dysplasia (FCD), a malformation of cortical development, is a frequent cause of drug-resistant epilepsy. This surgically-amenable lesion is histologically characterized by cortical dyslamination, dysmorphic neurons, and balloon cells, which may extend into the immediate subcortical white matter. On MRI, FCD is typically associated with cortical thickening, blurring of the cortical boundary, and intensity anomalies. Notably, even histologically-verified FCD may not be clearly visible on preoperative MRI. We propose a novel FCD detection algorithm, which aggregates surface-based descriptors of morphology and intensity derived from T1-weighted (T1w) MRI, T2-weighted fluid attenuation inversion recovery (FLAIR) MRI, and FLAIR/T1w ratio images. Features were systematically sampled at multiple intracortical/subcortical levels and fed into a two-stage classifier for automated lesion detection based on ensemble learning. Using 5-fold cross-validation, we evaluated the approach in 41 patients with histologically-verified FCD and 38 age-and sex-matched healthy controls. Our approach showed excellent sensitivity (83%, 34/41 lesions detected) and specificity (92%, no findings in 35/38 controls), suggesting benefits for presurgical diagnostics.

Research paper thumbnail of Deep Convolutional Networks for Automated Detection of Epileptogenic Brain Malformations

Focal cortical dysplasia (FCD) is a prevalent surgically-amenable epileptogenic malformation of c... more Focal cortical dysplasia (FCD) is a prevalent surgically-amenable epileptogenic malformation of cortical development. On MRI, FCD typically presents with cortical thickening, hyperintensity, and blurring of the gray-white matter interface. These changes may be visible to the naked eye, or subtle and be easily overlooked. Despite advances in MRI analytics, current surface-based algorithms fail to detect FCD in 50% of cases. Moreover, arduous data pre-processing and specialized expertise preclude widespread use. Here we propose a novel algorithm that harnesses feature-learning capability of convolutional neural networks (CNNs) with minimal data pre-processing. Our classifier, trained on a patch-based augmented dataset derived from patients with histologically-validated FCD operates directly on MRI voxels to distinguish the lesion from healthy tissue. The algorithm was trained and cross-validated on multimodal MRI data from a single site (S1) and evaluated on independent data from S1 a...

Research paper thumbnail of Decomposing MRI phenotypic heterogeneity in epilepsy: a step towards personalized classification

Brain, 2021

In drug-resistant temporal lobe epilepsy, precise predictions of drug response, surgical outcome ... more In drug-resistant temporal lobe epilepsy, precise predictions of drug response, surgical outcome and cognitive dysfunction at an individual level remain challenging. A possible explanation may lie in the dominant ‘one-size-fits-all’ group-level analytical approaches that does not allow parsing interindividual variations along the disease spectrum. Conversely, analysing inter-patient heterogeneity is increasingly recognized as a step towards person-centred care. Here, we used unsupervised machine learning to estimate latent relations (or disease factors) from 3 T multimodal MRI features [cortical thickness, hippocampal volume, fluid-attenuated inversion recovery (FLAIR), T1/FLAIR, diffusion parameters] representing whole-brain patterns of structural pathology in 82 patients with temporal lobe epilepsy. We assessed the specificity of our approach against age- and sex-matched healthy individuals and a cohort of frontal lobe epilepsy patients with histologically verified focal cortical ...

Research paper thumbnail of MRI-Based Machine Learning Prediction Framework to Lateralize Hippocampal Sclerosis in Patients With Temporal Lobe Epilepsy

Neurology, 2021

Background and ObjectivesMRI fails to reveal hippocampal pathology in 30% to 50% of temporal lobe... more Background and ObjectivesMRI fails to reveal hippocampal pathology in 30% to 50% of temporal lobe epilepsy (TLE) surgical candidates. To address this clinical challenge, we developed an automated MRI-based classifier that lateralizes the side of covert hippocampal pathology in TLE.MethodsWe trained a surface-based linear discriminant classifier that uses T1-weighted (morphology) and T2-weighted and fluid-attenuated inversion recovery (FLAIR)/T1 (intensity) features. The classifier was trained on 60 patients with TLE (mean age 35.6 years, 58% female) with histologically verified hippocampal sclerosis (HS). Images were deemed to be MRI negative in 42% of cases on the basis of neuroradiologic reading (40% based on hippocampal volumetry). The predictive model automatically labeled patients as having left or right TLE. Lateralization accuracy was compared to electroclinical data, including side of surgery. Accuracy of the classifier was further assessed in 2 independent TLE cohorts with ...

Research paper thumbnail of Whole-brain multimodal MRI phenotyping of periventricular nodular heterotopia

Neurology, 2020

ObjectiveTo test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and ... more ObjectiveTo test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and function of cortical areas overlying the heterotopic gray matter are preferentially affected.MethodsWe studied a group of 40 patients with PVNH and normal-appearing cortex and compared their quantitative MRI markers of brain development, structure, and function to those of 43 age- and sex-matched healthy controls. Inspired by models of neocortical development suggesting that neuronal migration follows a curvilinear path to preserve topologic correspondence between the outer ventricular zone and the cortical surface, we computationally defined the overlying cortex using the Laplace equation and generated synthetic streamlines that link the ventricles, where nodules are located, and the neocortex.ResultsWe found multilobar cortical thickening encompassing prefrontal, latero-basal temporal, and temporoparietal cortices largely corresponding with the PVNH group-averaged map of the overlying ...

Research paper thumbnail of Comparative Neurocognitive Functions of Schizophrenics and temporal lobe epileptic Patients

Introduction : Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has b... more Introduction : Shared neuropathology hypothesis in schizophrenia and temporal lobe epilepsy has been introduced long term ago. Similar neuropathology leads to the analogous clinical features like neuropsychological features as an example. The aim of this study was to examine this hypothesis by the means of comparing neuropsychological functions in these two patient groups. Method : Present study consisted of 28 DSM_IV_TR schizophrenics and 29 patients with temporal lobe epilepsy recruited from Roozbeh, Razi and khatamolanbia hospital in Tehran by convenient sampling method. SCID in schizophrenic group and EEG, MRI in epileptic patients were taken in regard to diagnostic determination. Neuropsychological tests were taken later. Package of neuropsychological tests consisted of Modified Wisconsin Card Sorting Test, Stroop Color- Word Test, Logic Memory, Visual Reproduction and Digit Span subscales of Wechsler Memory Scale- Revised and Block Design, Vocabulary and Symbol Digit subscales...

Research paper thumbnail of Altered communication dynamics reflect cognitive deficits in temporal lobe epilepsy

Epilepsia, 2021

Although temporal lobe epilepsy (TLE) is recognized as a system‐level disorder, little work has i... more Although temporal lobe epilepsy (TLE) is recognized as a system‐level disorder, little work has investigated pathoconnectomics from a dynamic perspective. By leveraging computational simulations that quantify patterns of information flow across the connectome, we tested the hypothesis that network communication is abnormal in this condition, studied the interplay between hippocampal‐ and network‐level disease effects, and assessed associations with cognition.

Research paper thumbnail of 1H-MRS metabolite’s ratios show temporal alternation in temporal lobe seizure: Comparison between interictal and postictal phases

Epilepsy Research, 2016

PURPOSES To determine 1H-MRSI metabolites changes in interictal and postictal phases of patients ... more PURPOSES To determine 1H-MRSI metabolites changes in interictal and postictal phases of patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis and lateralization of seizure foci. MATERIALS AND METHODS MR spectroscopic imaging was performed in 5 adult patients with refractory temporal lobe epilepsy interictally and immediately after the seizure and in 4 adult control subjects. All patients underwent MR imaging and VideoEEG Monitoring. RESULTS The results showed statistically significant decreases in N-acetylaspartate/Creatine, N-acetylaspartate/Choline and N-acetylaspartate/(creatine+choline) immediately after ictus in ipsilateral hippocampus as compared with control data and contralateral hippocampus of patients while no statistically significant difference was presented in interictal phase. CONCLUSION The present study clearly indicates 1H-MRS abnormalities following an ictus of temporal lobe epilepsy with metabolite recovery in interictal phase. This finding suggests postictal 1H-MRS as a possible useful tool to assist in lateralizing and localizing of seizure foci in epileptic patients with structural lesions.

Research paper thumbnail of The Use of Proton MR Spectroscopy in Epilepsy: A Methodological Review

Frontiers in Biomedical Technologies

Magnetic Resonance Spectroscopy (MRS) has at least two major roles in the evaluation of epileptic... more Magnetic Resonance Spectroscopy (MRS) has at least two major roles in the evaluation of epileptic patients. First, MRS can help to understand the interaction between seizures and metabolic function. Thus, MRS is particularly interesting for basic science studies of seizures and epilepsy. Second, MRS can explain the nature of seizure control and/or provide localization information by measuring metabolic changes. So MRS can be used as a powerful complementary technique to structural MRI for diagnosis and assessment of response to therapy, and measurement of disease progression. The aim of this paper is to review the methodological aspects of 1H-MRS publications between 1994 to 2016, which utilized 1H-MRS in lateralizing the epileptogenic zone in lesional and non-lesional Temporal Lobe Epilepsy (TLE), Extra-Temporal Lobe Epilepsy (ETLE), and generalized epileptic patients to help the spectroscopist, magnetic resonance imaging technologists, and radiologists to improve the overall diagn...

Research paper thumbnail of Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study

NeuroImage, Jan 3, 2017

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map wide... more The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effect...

Research paper thumbnail of Developmental MRI markers cosegregate juvenile patients with myoclonic epilepsy and their healthy siblings

Neurology

ObjectiveMRI studies of genetic generalized epilepsies have mainly described group-level changes ... more ObjectiveMRI studies of genetic generalized epilepsies have mainly described group-level changes between patients and healthy controls. To determine the endophenotypic potential of structural MRI in juvenile myoclonic epilepsy (JME), we examined MRI-based cortical morphologic markers in patients and their healthy siblings.MethodsIn this prospective, cross-sectional study, we obtained 3T MRI in patients with JME, siblings, and controls. We mapped sulco-gyral complexity and surface area, morphologic markers of brain development, and cortical thickness. Furthermore, we calculated mean geodesic distance, a surrogate marker of cortico-cortical connectivity.ResultsCompared to controls, patients and siblings showed increased folding complexity and surface area in prefrontal and cingulate cortices. In these regions, they also displayed abnormally increased geodesic distance, suggesting network isolation and decreased efficiency, with strongest effects for limbic, fronto-parietal, and dorsal...

Research paper thumbnail of Cardiac arrest associated with epileptic seizures: A case report with simultaneous EEG and ECG

Epilepsy Behavior Case Reports, 2014

Ictal asystole is a rare, probably underestimated manifestation of epileptic seizures whose patho... more Ictal asystole is a rare, probably underestimated manifestation of epileptic seizures whose pathophysiology is still debated. This report describes two patients who had cardiac asystole at the end of their seizure. The first patient was a 13-year-old boy with complex partial seizures.. His MRI showed symmetrical signal abnormality in the bilateral parietooccipital lobe accompanied by mild gliosis and volume loss. During a 3-day long-term video-EEG monitoring, he had cardiac arrest at the end of one of his seizures that was secondarily generalized. The second one was a 42-year-old veteran with penetrating head trauma in the left frontal lobe due to shell injury. During long-term video-EEG monitoring, he had one generalized tonic-clonic seizure accompanied by bradycardia and cardiac asystole. Asystoles could have a role in the incidence of sudden unexpected death in epilepsy (SUDEP), meaning that the presence of ictal bradycardia is a risk factor for SUDEP. In cases of epileptic cardiac dysrhythmia, prolonged simultaneous EEG/ECG monitoring may be required. Cardiological investigation should be included in epilepsy management.