Ali Tabesh

Estimation of tensors and tensor-derived measures in diffusional kurtosis imaging.

This article presents two related advancements to the diffusional kurtosis imaging estimation framework to increase its robustness to noise, motion, and imaging artifacts. The first advancement substantially improves the estimation of diffusion and kurtosis tensors parameterizing the diffusional kurtosis imaging model. Rather than utilizing conventional unconstrained least squares methods, the tensor estimation problem is formulated as linearly constrained linear least squares, where the constraints ensure physically and/or biologically plausible tensor estimates. The exact solution to the constrained problem is found via convex quadratic programming methods or, alternatively, an approximate solution is determined through a fast heuristic algorithm. The computationally more demanding quadratic programming‐based method is more flexible, allowing for an arbitrary number of diffusion weightings and different gradient sets for each diffusion weighting. The heuristic algorithm is suitable for real‐time settings such as on clinical scanners, where run time is crucial. The advantage offered by the proposed constrained algorithms is demonstrated using in vivo human brain images. The proposed constrained methods allow for shorter scan times and/or higher spatial resolution for a given fidelity of the diffusional kurtosis imaging parametric maps. The second advancement increases the efficiency and accuracy of the estimation of mean and radial kurtoses by applying exact closed‐form formulae. Magn Reson Med, 2011.

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.

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.

Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction.

By application of the MRI method of diffusional kurtosis imaging, a substantially increased diffusional kurtosis was observed within the cerebral ischemic lesions of three stroke subjects, 13–26 h following the onset of symptoms. This increase is interpreted as probably reflecting a higher degree of diffusional heterogeneity in the lesions when compared with normal‐appearing contralateral tissue. In addition, for two of the subjects with white matter infarcts, the increase had a strong fiber tract orientational dependence. It is proposed that this effect is consistent with a large drop in the intra‐axonal diffusivity, possibly related to either axonal varicosities or alterations associated with the endoplasmic reticulum. Copyright

Cognitive Impairment in Mild Traumatic Brain Injury: A Longitudinal Diffusional Kurtosis and Perfusion Imaging Study

DTI, diffusional kurtosis, and arterial spin-labeling were used in an attempt to detect abnormalities in 20 patients shortly after mild traumatic brain injury. These patients were also evaluated for attention, concentration, executive functioning, memory, learning, and information processing. At 1 and 9 months after injury, all patients showed significant abnormalities in gray and white matter by using all techniques and thus these methods may be useful in investigating cognitive impairment after brain injury. BACKGROUND AND PURPOSE: Cognitive impairment is frequent among patients with mild traumatic brain injury despite the absence of detectable damage on conventional MR imaging. In this study, the quantitative MR imaging techniques DTI, DKI, and ASL were used to measure changes in the structure and function in the thalamus and WM of patients with MTBI during a short follow-up period, to determine whether these techniques can be used to investigate relationships with cognitive performance and to predict outcome. MATERIALS AND METHODS: Twenty patients with MTBI and 16 controls underwent MR imaging at 3T and a neuropsychological battery designed to yield measures for attention, concentration, executive functioning, memory, learning, and information processing. MK, FA, MD, and CBF were measured in the thalamus by using region-of-interest analysis and in WM by using tract-based spatial statistics. Analyses were performed comparing regional imaging measures of subject groups and the results of testing of their associations with neuropsychological performance. RESULTS: Patients with MTBI exhibited significant differences from controls for DTI, DKI, and ASL measures in the thalamus and various WM regions both within 1 month after injury and >9 months after injury. At baseline, DTI and DKI measures in the thalamus and various WM regions were significantly associated with performance in different neuropsychological domains, and cognitive impairment was significantly associated with MK in the thalamus and FA in optic radiations. CONCLUSIONS: Combined application of DTI, DKI, and ASL to study MTBI might be useful for investigating dynamic changes in the thalamus and WM as well as cognitive impairment during a short follow-up period, though the small number of patients examined did not predict outcome.

Novel White Matter Tract Integrity Metrics Sensitive to Alzheimer Disease Progression

BACKGROUND AND PURPOSE: Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. MATERIALS AND METHODS: This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. RESULTS: With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82–0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80–0.82|, P < .001). CONCLUSIONS: These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.

Diffusion Tensor Imaging Reliably Differentiates Patients With Schizophrenia from Healthy Volunteers

The objective of this research was to determine whether fractional anisotropy (FA) and mean diffusivity (MD) maps derived from diffusion tensor imaging (DTI) of the brain are able to reliably differentiate patients with schizophrenia from healthy volunteers. DTI and high resolution structural magnetic resonance scans were acquired in 50 patients with schizophrenia and 50 age‐ and sex‐matched healthy volunteers. FA and MD maps were estimated from the DTI data and spatially normalized to the Montreal Neurologic Institute standard stereotactic space. Individuals were divided randomly into two groups of 50, a training set, and a test set, each comprising 25 patients and 25 healthy volunteers. A pattern classifier was designed using Fishers linear discriminant analysis (LDA) based on the training set of images to categorize individuals in the test set as either patients or healthy volunteers. Using the FA maps, the classifier correctly identified 94% of the cases in the test set (96% sensitivity and 92% specificity). The classifier achieved 98% accuracy (96% sensitivity and 100% specificity) when using the MD maps as inputs to distinguish schizophrenia patients from healthy volunteers in the test dataset. Utilizing FA and MD data in combination did not significantly alter the accuracy (96% sensitivity and specificity). Patterns of water self‐diffusion in the brain as estimated by DTI can be used in conjunction with automated pattern recognition algorithms to reliably distinguish between patients with schizophrenia and normal control subjects. Hum Brain Mapp, 2010.

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.

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.

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.