Early assessment of recurrent glioblastoma response to bevacizumab treatment by diffusional kurtosis imaging: a preliminary report.

PURPOSE: The purpose of this preliminary study is to apply diffusional kurtosis imaging to assess the early response of recurrent glioblastoma to bevacizumab treatment. METHODS: This prospective cohort study included 10 patients who had been diagnosed with recurrent glioblastoma and scheduled to receive bevacizumab treatment. Diffusional kurtosis images were obtained from all the patients 0-7 days before (pre-bevacizumab) and 28 days after (post-bevacizumab) initiating bevacizumab treatment. The mean, 10th, and 90th percentile values were derived from the histogram of diffusional kurtosis imaging metrics in enhancing and non-enhancing lesions, selected on post-contrast T1-weighted and fluid-attenuated inversion recovery images. Correlations of imaging measures with progression-free survival and overall survival were evaluated using Spearman's rank correlation coefficient. The significance level was set at P < 0.05. RESULTS: Higher pre-bevacizumab non-enhancing lesion volume was correlated with poor overall survival (r = -0.65, P = 0.049). Higher post-bevacizumab mean diffusivity and axial diffusivity (D∥, D∥10% and D∥90%) in non-enhancing lesions were correlated with poor progression-free survival (r = -0.73, -0.83, -0.71 and -0.85; P < 0.05). Lower post-bevacizumab axial kurtosis (K∥10%) in non-enhancing lesions was correlated with poor progression-free survival (r = 0.81, P = 0.008). CONCLUSIONS: This preliminary study demonstrates that diffusional kurtosis imaging metrics allow the detection of tissue changes 28 days after initiating bevacizumab treatment and that they may provide information about tumor progression.

Perilesional apparent diffusion coefficient in the preoperative evaluation of glioma grade.

Preoperative identification of high-grade gliomas is critical to optimize treatment strategy and to predict prognosis. To determine whether perilesional apparent diffusion coefficient (ADC) values differ between high- and low-grade tumors, we assessed water diffusivity within normal-appearing brain parenchyma (NABP) surrounding gliomas in twenty-one treatment-naïve patients. This showed significantly lower mean and 25th percentile (Q1) ADC values in high- grade compared to low-grade gliomas respectively in the range of 10-25 and 10-30 mm away from combined tumor and surrounding T2 signal. Thus, perilesional ADC measurement may reflect the extent of tumor infiltration beyond the abnormality seen on conventional MRI.

Optimization of white matter fiber tractography with diffusional kurtosis imaging.

Diffusional kurtosis imaging (DKI) is a clinically feasible diffusion MRI technique for white matter (WM) fiber tractography (FT) with the ability to directly resolve intra-voxel crossing fibers by means of the kurtosis diffusion orientation distribution function (dODF). Here we expand on previous work by exploring properties of the kurtosis dODF and their subsequent effects on WM FT for in vivo human data. For comparison, the results are contrasted with fiber bundle orientation estimates provided by the diffusion tensor, which is the primary quantity obtained from diffusion tensor imaging. We also outline an efficient method for performing DKI-based WM FT that can substantially decrease the computational requirements. The recommended method for implementing the kurtosis ODF is demonstrated to optimize the reproducibility and sensitivity of DKI for detecting crossing fibers while reducing the occurrence of non-physically-meaningful, negative values in the kurtosis dODF approximation. In addition, DKI-based WM FT is illustrated for different protocols differing in image acquisition times from 48 to 5.3 min.

Instituting a radiology residency scholarly activity program.

BACKGROUND: The purpose of this manuscript is to present a newly instituted program for resident scholarly activity that includes a curriculum designed to enhance resident training with regard to research while meeting requirements established by the Accreditation Council for Graduate Medical Education (ACGME), the governing body responsible for regulation of post-graduate medical education and training in the United States. METHODS: A scholarly activity program was designed with the following goals: (i) enhance the academic training environment for our residents; (ii) foster interests in research and academic career paths; (iii) provide basic education on research methodology and presentation skills. To guide program design, an electronic survey was created and distributed to the residents and faculty in the Department of Radiology and Radiological Sciences at the Medical University of South Carolina (MUSC), a 750-bed public teaching hospital in the state of South Carolina in the United States. RESULTS: Survey respondents were in strong support of a required resident scholarly activity project (70% in favor), felt non-traditional projects were valuable (84.1% of respondents), and were proponents of required scholarly activity summary presentations (58%). This program requires that residents engage in a scholarly activity project under the guidance of a mentor. Resident success is maximized through in-house education initiatives focusing on presentation and research skills, protected time to work on the project, and oversight by a radiology research committee. All residents present a summary of their work near the end of their residency training. DISCUSSION: Changes to the radiology resident certification process create an opportunity for incorporating new policies aimed at enhancing resident education. The scholarly activity program outlined in this manuscript is one such initiative designed to meet ACGME requirements, provide an introduction to research, and establish a scholarly activity project requirement.

Quantitative assessment of diffusional kurtosis anisotropy.

Diffusional kurtosis imaging (DKI) measures the diffusion and kurtosis tensors to quantify restricted, non-Gaussian diffusion that occurs in biological tissue. By estimating the kurtosis tensor, DKI accounts for higher order diffusion dynamics, when compared with diffusion tensor imaging (DTI), and consequently can describe more complex diffusion profiles. Here, we compare several measures of diffusional anisotropy which incorporate information from the kurtosis tensor, including kurtosis fractional anisotropy (KFA) and generalized fractional anisotropy (GFA), with the diffusion tensor-derived fractional anisotropy (FA). KFA and GFA demonstrate a net enhancement relative to FA when multiple white matter fiber bundle orientations are present in both simulated and human data. In addition, KFA shows net enhancement in deep brain structures, such as the thalamus and the lenticular nucleus, where FA indicates low anisotropy. Thus, KFA and GFA provide additional information relative to FA with regard to diffusional anisotropy, and may be particularly advantageous for the assessment of diffusion in complex tissue environments.

A simple noise correction scheme for diffusional kurtosis imaging.

PURPOSE: Diffusional kurtosis imaging (DKI) is sensitive to the effects of signal noise due to strong diffusion weightings and higher order modeling of the diffusion weighted signal. A simple noise correction scheme is proposed to remove the majority of the noise bias in the estimated diffusional kurtosis. METHODS: Weighted linear least squares (WLLS) fitting together with a voxel-wise, subtraction-based noise correction from multiple, independent acquisitions are employed to reduce noise bias in DKI data. The method is validated in phantom experiments and demonstrated for in vivo human brain for DKI-derived parameter estimates. RESULTS: As long as the signal-to-noise ratio (SNR) for the most heavily diffusion weighted images is greater than 2.1, errors in phantom diffusional kurtosis estimates are found to be less than 5 percent with noise correction, but as high as 44 percent for uncorrected estimates. In human brain, noise correction is also shown to improve diffusional kurtosis estimates derived from measurements made with low SNR. CONCLUSION: The proposed correction technique removes the majority of noise bias from diffusional kurtosis estimates in noisy phantom data and is applicable to DKI of human brain. Features of the method include computational simplicity and ease of integration into standard WLLS DKI post-processing algorithms.

Human brain asymmetry in microstructural connectivity demonstrated by diffusional kurtosis imaging.

Structural asymmetry of whole brain white matter (WM) pathways, i.e., the connectome, has been demonstrated using fiber tractography based on diffusion tensor imaging (DTI). However, DTI-based tractography fails to resolve axonal fiber bundles that intersect within an imaging voxel, and therefore may not fully characterize the extent of asymmetry. The goal of this study was to assess structural asymmetry with tractography based on diffusional kurtosis imaging (DKI), which improves upon DTI-based tractography by delineating intravoxel crossing fibers. DKI images were obtained from 42 healthy subjects. By using automatic segmentation, gray matter (GM) was parcellated into anatomically defined regions of interest (ROIs). WM pathways were reconstructed with both DKI- and DTI-based tractography. The connectivity between the ROIs was quantified with the streamlines connecting the ROIs. The asymmetry index (AI) was utilized to quantify hemispheric differences in the connectivity of cortical ROIs and of links interconnecting cortical ROIs. Our results demonstrated that leftward asymmetrical ROIs and links were observed in frontal, parietal, temporal lobes, and insula. Rightward asymmetrical ROI and links were observed in superior frontal lobe, cingulate cortex, fusiform, putamen, and medial temporal lobe. Interestingly, these observed structural asymmetries were incompletely identified with DTI-based tractography. These results suggest that DKI-based tractography can improve the identification of asymmetrical connectivity patterns, thereby serving as an additional tool in the evaluation of the structural bases of functional lateralization.

Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination.

The cuprizone mouse model is well established for studying the processes of both demyelination and remyelination in the corpus callosum, and it has been utilized together with diffusion tensor imaging (DTI) to investigate myelin and axonal pathology. Although some underlying morphological mechanisms contributing to the changes in diffusion tensor (DT) metrics have been identified, the understanding of specific associations between histology and diffusion measures remains limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides metrics of diffusional non-Gaussianity, for which an associated white matter modeling (WMM) method has been developed. The main goal of the present study was to quantitatively assess the relationships between diffusion measures and histological measures in the mouse model of cuprizone-induced corpus callosum demyelination. The diffusional kurtosis (DK) and WMM metrics were found to provide additional information that enhances the sensitivity to detect the morphological heterogeneity in the chronic phase of the disease process in the rostral segment of the corpus callosum. Specifically, in the rostral segment, axonal water fraction (d = 2.6; p < 0.0001), radial kurtosis (d = 2.0; p = 0.001) and mean kurtosis (d = 1.5; p = 0.005) showed the most sensitivity between groups with respect to yielding statistically significant p values and high Cohen's d values. These results demonstrate the ability of DK and WMM metrics to detect white mater changes and inflammatory processes associated with cuprizone-induced demyelination. They also validate, in part, the application of these new WMM metrics for studying neurological diseases, as well as helping to elucidate their biophysical meaning.

Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment?

PURPOSE: To comprehensively assess brain iron levels in typically developing control subjects and patients with attention deficit hyperactivity disorder (ADHD) when psychostimulant medication history is accounted for. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and informed consent was obtained. Brain iron was indexed noninvasively by using magnetic resonance (MR) imaging relaxation rates (R2, R2*, R2') and magnetic field correlation (MFC) in the globus pallidus, putamen, caudate nucleus, and thalamus for 22 patients with ADHD (12 medication-naïve patients and 10 with a history of psychostimulant treatment) and 27 control subjects (age range, 8-18 years). Serum iron measures were also collected. Subgroup differences were analyzed with data-appropriate omnibus tests followed by post hoc pairwise comparisons; false discovery rate correction was conducted to control for multiple comparisons. RESULTS: Medication-naïve ADHD patients had significantly lower striatal and thalamic MFC indexes of brain iron than did control subjects (putamen, P = .012; caudate nucleus, P = .008; thalamus, P = .012) and psychostimulant-medicated ADHD patients (putamen, P = .006; caudate nucleus, P = .010; thalamus, P = .021). Conversely, the MFC indexes in medicated patients were comparable to those in control subjects. No significant differences were detected with R2, R2*, R2', or serum measures. CONCLUSION: Lower MFC indexes of striatal and thalamic brain iron in medication-naïve ADHD patients and lack of differences in psychostimulant-medicated patients suggest that MFC indexes of brain iron may represent a noninvasive diagnostic biomarker that responds to psychostimulant treatment.

Leading non-Gaussian corrections for diffusion orientation distribution function.

An analytical representation of the leading non-Gaussian corrections for a class of diffusion orientation distribution functions (dODFs) is presented. This formula is constructed from the diffusion and diffusional kurtosis tensors, both of which may be estimated with diffusional kurtosis imaging (DKI). By incorporating model-independent non-Gaussian diffusion effects, it improves on the Gaussian approximation used in diffusion tensor imaging (DTI). This analytical representation therefore provides a natural foundation for DKI-based white matter fiber tractography, which has potential advantages over conventional DTI-based fiber tractography in generating more accurate predictions for the orientations of fiber bundles and in being able to directly resolve intra-voxel fiber crossings. The formula is illustrated with numerical simulations for a two-compartment model of fiber crossings and for human brain data. These results indicate that the inclusion of the leading non-Gaussian corrections can significantly affect fiber tractography in white matter regions, such as the centrum semiovale, where fiber crossings are common.

Neurodevelopmental alterations of large-scale structural networks in children with new-onset epilepsy.

Recent neuroimaging and behavioral studies have revealed that children with new onset epilepsy already exhibit brain structural abnormalities and cognitive impairment. How the organization of large-scale brain structural networks is altered near the time of seizure onset and whether network changes are related to cognitive performances remain unclear. Recent studies also suggest that regional brain volume covariance reflects synchronized brain developmental changes. Here, we test the hypothesis that epilepsy during early-life is associated with abnormalities in brain network organization and cognition. We used graph theory to study structural brain networks based on regional volume covariance in 39 children with new-onset seizures and 28 healthy controls. Children with new-onset epilepsy showed a suboptimal topological structural organization with enhanced network segregation and reduced global integration compared with controls. At the regional level, structural reorganization was evident with redistributed nodes from the posterior to more anterior head regions. The epileptic brain network was more vulnerable to targeted but not random attacks. Finally, a subgroup of children with epilepsy, namely those with lower IQ and poorer executive function, had a reduced balance between network segregation and integration. Taken together, the findings suggest that the neurodevelopmental impact of new onset childhood epilepsies alters large-scale brain networks, resulting in greater vulnerability to network failure and cognitive impairment.

White matter tract integrity metrics reflect the vulnerability of late-myelinating tracts in Alzheimer's disease.

Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD.

Attention-deficit/hyperactivity disorder without comorbidity is associated with distinct atypical patterns of cerebral microstructural development.

Differential core symptoms and treatment responses are associated with the pure versus comorbid forms of attention-deficit/hyperactivity disorder (ADHD). However, comorbidity has largely been unaccounted for in neuroimaging studies of ADHD. We used diffusional kurtosis imaging to investigate gray matter (GM) and white matter (WM) microstructure of children and adolescents with ADHD (n = 22) compared to typically developing controls (TDC, n = 27) and examined whether differing developmental patterns are related to comorbidity. The ADHD group (ADHD-mixed) consisted of subgroups with and without comorbidity (ADHD-comorbid, n = 11; ADHD-pure, n = 11, respectively). Age-related changes and group differences in cerebral microstructure of the ADHD-mixed group and each ADHD subgroup were compared to TDC. Whole-brain voxel-based analyses with mean kurtosis (MK) and mean diffusivity (MD) metrics were conducted to probe GM and WM. Tract-based spatial statistics analyses of WM were performed with MK, MD, fractional anisotropy, and directional (axial, radial) kurtosis and diffusivity metrics. ADHD-pure patients lacked significant age-related changes in GM and WM microstructure that were observed globally in TDC and had significantly greater WM microstructural complexity than TDC in bilateral frontal and parietal lobes, insula, corpus callosum, and right external and internal capsules. Including ADHD patients with diverse comorbidities in analyses masked these findings. A distinct atypical age-related trajectory and aberrant regional differences in brain microstructure were detected in ADHD without comorbidity. Our results suggest that different phenotypic manifestations of ADHD, defined by the presence or absence of comorbidity, differ in cerebral microstructural markers.

Presurgical connectome and postsurgical seizure control in temporal lobe epilepsy.

OBJECTIVES: The objective of this study was to evaluate whether patients with surgically refractory medial temporal lobe epilepsy (MTLE) exhibit a distinct pattern of structural network organization involving the temporal lobes and extratemporal regions. METHODS: We retrospectively studied 18 healthy controls and 20 patients with medication refractory unilateral MTLE who underwent anterior temporal lobectomy for treatment of seizures. Patients were classified as seizure-free or not seizure-free at least 1 year after surgery. The presurgical brain connectome was calculated through probabilistic connectivity from MRI-diffusion tensor imaging from 83 anatomically defined regions of interest encompassing the whole brain. The connectivity patterns were analyzed regarding group differences in regional connectivity and network graph properties. RESULTS: Compared with controls, patients exhibited a decrease in connectivity involving ipsilateral thalamocortical regions, with a pathologic increase in ipsilateral medial temporal lobe, insular, and frontal connectivity. Among patients, those not seizure-free exhibited a higher connectivity between structures in 1) the ipsilateral medial and lateral temporal lobe, 2) the ipsilateral medial temporal and parietal lobe, and 3) the contralateral temporal pole and parietal lobe. Patients not seizure-free also exhibited lower small-worldness in the subnetwork within the ipsilateral temporal lobe, with higher subnetwork integration at the expense of segregation. CONCLUSIONS: MTLE is associated with network rearrangement within, but not restricted to, the temporal lobe ipsilateral to the onset of seizures. Networks involving key components of the medial temporal lobe and structures traditionally not removed during surgery may be associated with seizure control after surgical treatment of MTLE.

Microstructural integrity of early- versus late-myelinating white matter tracts in medial temporal lobe epilepsy.

PURPOSE: Patients with medial temporal lobe epilepsy (MTLE) exhibit structural brain damage involving gray matter (GM) and white matter (WM). The mechanisms underlying tissue loss in MTLE are unclear and may be associated with a combination of seizure excitotoxicity and WM vulnerability. The goal of this study was to investigate whether late-myelinating WM tracts are more vulnerable to injury in MTLE compared with early myelinating tracts. METHODS: Diffusional kurtosis imaging scans were obtained from 25 patients with MTLE and from 36 matched healthy controls. Diffusion measures from regions of interest (ROIs) for both late- and early myelinating WM tracts were analyzed. Regional Z-scores were computed with respect to normal controls to compare WM in early myelinating tracts versus late-myelinating tracts. KEY FINDINGS: We observed that late-myelinating tracts exhibited a larger decrease in mean, axial, and radial kurtosis compared with early myelinating tracts. We also observed that the change in radial kurtosis was more pronounced in late-myelinating tracts ipsilateral to the side of seizure onset. SIGNIFICANCE: These results suggest a developmentally based preferential susceptibility of late-myelinating WM tracts to damage in MTLE. Brain injury in epilepsy may be due to the pathologic effects of seizures in combination with regional WM vulnerability.

Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer's disease.

We report the first application of a novel diffusion-based MRI method, called diffusional kurtosis imaging (DKI), to investigate changes in brain tissue microstructure in patients with mild cognitive impairment (MCI) and AD and in cognitively intact controls. The subject groups were characterized and compared in terms of DKI-derived metrics for selected brain regions using analysis of covariance with a Tukey multiple comparison correction. Receiver operating characteristic (ROC) and binary logistic regression analyses were used to assess the utility of regional diffusion measures, alone and in combination, to discriminate each pair of subject groups. ROC analyses identified mean and radial kurtoses in the anterior corona radiata as the best individual discriminators of MCI from controls, with the measures having an area under the ROC curve (AUC) of 0.80 and 0.82, respectively. The next best discriminators of MCI from controls were diffusivity and kurtosis (both mean and radial) in the prefrontal white matter (WM), with each measure having an AUC between 0.77 and 0.79. Finally, the axial diffusivity in the hippocampus was the best overall discriminator of MCI from AD, having an AUC of 0.90. These preliminary results suggest that non-Gaussian diffusion MRI may be beneficial in the assessment of microstructural tissue damage at the early stage of MCI and may be useful in developing biomarkers for the clinical staging of AD.

Perfusion network shift during seizures in medial temporal lobe epilepsy.

BACKGROUND: Medial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, peri-hippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE. METHODS: We studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations. RESULTS: A significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration. CONCLUSIONS: These results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE.

Effect of cerebral spinal fluid suppression for diffusional kurtosis imaging.

PURPOSE: To evaluate the cerebral spinal fluid (CSF) partial volume effect on diffusional kurtosis imaging (DKI) metrics in white matter and cortical gray matter. MATERIALS AND METHODS: Four healthy volunteers participated in this study. Standard DKI and fluid-attenuated inversion recovery (FLAIR) DKI experiments were performed using a twice-refocused-spin-echo diffusion sequence. The conventional diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, D[symbol in text], D[symbol in text] together with DKI metrics of mean, axial, and radial kurtosis (MK, K[symbol in text], K[symbol in text], were measured and compared. Single image slices located above the lateral ventricles, with similar anatomical features for each subject, were selected to minimize the effect of CSF from the ventricles. RESULTS: In white matter, differences of less than 10% were observed between diffusion metrics measured with standard DKI and FLAIR-DKI sequences, suggesting minimal CSF contamination. For gray matter, conventional DTI metrics differed by 19% to 52%, reflecting significant CSF partial volume effects. Kurtosis metrics, however, changed by 11% or less, indicating greater robustness with respect to CSF contamination. CONCLUSION: Kurtosis metrics are less sensitive to CSF partial voluming in cortical gray matter than conventional diffusion metrics. The kurtosis metrics may then be more specific indicators of changes in tissue microstructure, provided the effect sizes for the changes are comparable.

Stroke assessment with diffusional kurtosis imaging.

BACKGROUND AND PURPOSE: Despite being the gold standard technique for stroke assessment, conventional diffusion MRI provides only partial information about tissue microstructure. Diffusional kurtosis imaging is an advanced diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis, which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics. The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WM metrics. METHODS: We performed a retrospective review of clinical and diffusional kurtosis imaging data of 44 patients with acute/subacute ischemic stroke. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. Region of interest analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared with the contralateral hemisphere. RESULTS: Kurtosis maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient maps. Kurtosis metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WM metrics reveal an increase in axonal density and a larger decrease in the intra-axonal (Da) compared with extra-axonal diffusion microenvironment of the ischemic WM lesion. CONCLUSIONS: The well-known decrease in the apparent diffusion coefficient of WM after ischemia is found to be mainly driven by a significant drop in the intra-axonal diffusion microenvironment. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.

Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures.

BACKGROUND: It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis. METHODS: 12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls. RESULTS: MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree. CONCLUSIONS: These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.