Reduced local diffusion homogeneity as a biomarker for temporal lobe epilepsy.
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ABSTRACT:
SUBMITTER: Liu HH
PROVIDER: S-EPMC5265813 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Reduced local diffusion homogeneity as a biomarker for temporal lobe epilepsy.
Liu Hui-Hua HH Wang Jun J Chen Xue-Mei XM Li Jian-Ping JP Ye Wei W Zheng Jinou J
Medicine 20160701 30
In the present study, we adopted a novel method-local diffusion homogeneity (LDH)-to characterize the structure feature in mesial temporal lobe epilepsy (MTLE). Diffusion-weighted images were acquired from 11 left MTLE patients, 16 right MTLE patients, and 20 healthy controls from May 2014 to January 2015. Local diffusion homogeneity was compared among patient groups and controls by 2 sample t test. The discriminative value of LDH abnormalities was examined by receiver operating characteristic ( ...[more]
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Project description:Temporal lobe epilepsy (TLE) is often associated with progressive changes to seizures, memory, and mood during its clinical course. However, the cerebral changes related to this progression are not well understood. Because the changes may be related to changes in brain networks, we used functional connectivity MRI (fcMRI) to determine whether brain network parameters relate to the duration of TLE. Graph theory-based analysis of the sites of reported regions of TLE abnormality was performed on resting-state fMRI data in 48 subjects: 24 controls, 13 patients with left TLE, and 11 patients with right TLE. Various network parameters were analyzed including betweenness centrality (BC), clustering coefficient (CC), path length (PL), small-world index (SWI), global efficiency (GE), connectivity strength (CS), and connectivity diversity (CD). These were compared for patients with TLE as a group, compared to controls, and for patients with left and right TLE separately. The association of changes in network parameters with epilepsy duration was also evaluated. We found that CC, CS, and CD decreased in subjects with TLE compared to control subjects. Analyzed according to epilepsy duration, patients with TLE showed a progressive reduction in CD. In conclusion, we found that several network parameters decreased in patients with TLE compared to controls, which suggested reduced connectivity in TLE. Reduction in CD associated with epilepsy duration suggests a homogenization of connections over time in TLE, indicating a reduction of the normal repertoire of stronger and weaker connections to other brain regions.
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Project description:PurposePrevious imaging studies in patients with refractory temporal lobe epilepsy (TLE) have examined the spatial distribution of changes in imaging parameters such as diffusion tensor imaging (DTI) metrics and cortical thickness. Multi-compartment models offer greater specificity with parameters more directly related to known changes in TLE such as altered neuronal density and myelination. We studied the spatial distribution of conventional and novel metrics including neurite density derived from NODDI (Neurite Orientation Dispersion and Density Imaging) and myelin water fraction (MWF) derived from mcDESPOT (Multi-Compartment Driven Equilibrium Single Pulse Observation of T1/T2)] to infer the underlying neurobiology of changes in conventional metrics.Methods20 patients with TLE and 20 matched controls underwent magnetic resonance imaging including a volumetric T1-weighted sequence, multi-shell diffusion from which DTI and NODDI metrics were derived and a protocol suitable for mcDESPOT fitting. Models of the grey matter-white matter and grey matter-CSF surfaces were automatically generated from the T1-weighted MRI. Conventional diffusion and novel metrics of neurite density and MWF were sampled from intracortical grey matter and subcortical white matter surfaces and cortical thickness was measured.ResultsIn intracortical grey matter, diffusivity was increased in the ipsilateral temporal and frontopolar cortices with more restricted areas of reduced neurite density. Diffusivity increases were largely related to reductions in neurite density, and to a lesser extent CSF partial volume effects, but not MWF. In subcortical white matter, widespread bilateral reductions in fractional anisotropy and increases in radial diffusivity were seen. These were primarily related to reduced neurite density, with an additional relationship to reduced MWF in the temporal pole and anterolateral temporal neocortex. Changes were greater with increasing epilepsy duration. Bilaterally reduced cortical thickness in the mesial temporal lobe and centroparietal cortices was unrelated to neurite density and MWF.ConclusionsDiffusivity changes in grey and white matter are primarily related to reduced neurite density with an additional relationship to reduced MWF in the temporal pole. Neurite density may represent a more sensitive and specific biomarker of progressive neuronal damage in refractory TLE that deserves further study.
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Project description:Ion channel splice array data collected from temporal neocortex brain tissue collected from patients with mesial temporal lobe epilepsy. Temporal cortex samples from control subjects were compared to temporal neocortex of patients with mesial temporal lobe epilepsy
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Project description:BackgroundIt is common for patients diagnosed with medial temporal lobe epilepsy (TLE) to have extrahippocampal damage. However, it is unclear whether microstructural extrahippocampal abnormalities are consistent enough to enable classification using diffusion MRI imaging. Therefore, we implemented a support vector machine (SVM)-based method to predict TLE from three different imaging modalities: mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA). While MD and FA can be calculated from traditional diffusion tensor imaging (DTI), MK requires diffusion kurtosis imaging (DKI).MethodsThirty-two TLE patients and 36 healthy controls underwent DKI imaging. To measure predictive capability, a fivefold cross-validation (CV) was repeated for 1000 iterations. An ensemble of SVM models, each with a different regularization value, was trained with the subject images in the training set, and had performance assessed on the test set. The different regularization values were determined using a Bayesian-based method.ResultsMean kurtosis achieved higher accuracy than both FA and MD on every iteration, and had far superior average accuracy: 0.82 (MK), 0.68 (FA), and 0.51 (MD). Finally, the MK voxels with the highest coefficients in the predictive models were distributed within the inferior medial aspect of the temporal lobes.ConclusionThese results corroborate our earlier publications which indicated that DKI shows more promise in identifying TLE-associated pathological features than DTI. Also, the locations of the contributory MK voxels were in areas with high fiber crossing and complex fiber anatomy. These traits result in non-Gaussian water diffusion, and hence render DTI less likely to detect abnormalities. If the location of consistent microstructural abnormalities can be better understood, then it may be possible in the future to identify the various phenotypes of TLE. This is important since treatment outcome varies dependent on type of TLE.
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Project description:ObjectiveThe objective of the present study is to identify novel, time-indexed imaging biomarkers of epileptogenesis in mesial temporal lobe epilepsy (MTLE).MethodsWe used high-resolution brain diffusion tensor imaging (DTI) of the translationally relevant methionine sulfoximine (MSO) brain infusion model of MTLE. MSO inhibits astroglial glutamine synthetase, which is deficient in the epileptogenic hippocampal formation of patients with MTLE. MSO-infused (epileptogenic) rats were compared with phosphate-buffered saline (PBS)-infused (nonepileptogenic) rats at early (3-4 days) and late (6-9 weeks) time points during epileptogenesis.ResultsThe epileptogenic rats exhibited significant changes in DTI-measured fractional anisotropy (FA) in numerous brain regions versus nonepileptogenic rats. Changes included decreases and increases in FA in regions such as the entorhinal-hippocampal area, amygdala, corpus callosum, thalamus, striatum, accumbens, and neocortex. The FA changes evolved over time as animals transitioned from early to late epileptogenesis. For example, some areas with significant decreases in FA early in epileptogenesis changed to significant increases late in epileptogenesis. Finally, the FA changes significantly correlated with the seizure load.SignificanceOur results suggest (1) that high-resolution DTI can be used for early identification and tracking of the epileptogenic process in MTLE, and (2) that the process identified by DTI is present in multiple brain areas, even though infusion of MSO is restricted to the unilateral entorhinal-hippocampal region.
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