Alina Jurcoane

Diffusion tensor imaging in patients with adult chronic idiopathic hydrocephalus.

OBJECTIVEDiffusion tensor imaging (DTI) parameters were investigated in patients with chronic idiopathic hydrocephalus to evaluate microstructural changes of brain tissue caused by chronic ventricular dilatation. METHODSEleven patients fulfilling the criteria for possible or probable idiopathic normal pressure hydrocephalus and 10 healthy control subjects underwent MRI at 3 Tesla, including DTI with 12 gradient directions. Patients were scanned before lumbar cerebrospinal fluid (CSF) withdrawal tests. Differences in fractional anisotropy (FA) and mean diffusivity (MD) between patients and controls were assessed using 2 different methods: manual definition of regions of interest and a fully automated method, TBSS (Tract-Based Spatial Statistics). DTI parameters were correlated with clinical findings. RESULTSCompared with the control group, patients with chronic idiopathic hydrocephalus had significantly higher MD values in both the periventricular corticospinal tract (CST) and the corpus callosum (CC), whereas FA values were significantly higher in the CST but lower in the CC. DTI parameters of the CST correlated with the severity of gait disturbances. CONCLUSIONMicrostructural changes in periventricular functionally relevant white matter structures (CSF, CC) in chronic idiopathic hydrocephalus can be visualized using DTI. Further studies should investigate the change of DTI parameters after CSF shunting and its relation to neurologic outcome.

Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disorder of the central nervous system characterized by multifocal white matter brain lesions leading to alterations in connectivity at the subcortical and cortical level. Graph theory, in combination with neuroimaging techniques, has been recently developed into a powerful tool to assess the large-scale structure of brain functional connectivity. Considering the structural damage present in the brain of MS patients, we hypothesized that the topological properties of resting-state functional networks of early MS patients would be re-arranged in order to limit the impact of disease expression. A standardized dual task (Paced Auditory Serial Addition Task simultaneously performed with a paper and pencil task) was administered to study the interactions between behavioral performance and functional network re-organization. We studied a group of 16 early MS patients (35.3±8.3 years, 11 females) and 20 healthy controls (29.9±7.0 years, 10 females) and found that brain resting-state networks of the MS patients displayed increased network modularity, i.e. diminished functional integration between separate functional modules. Modularity correlated negatively with dual task performance in the MS patients. Our results shed light on how localized anatomical connectivity damage can globally impact brain functional connectivity and how these alterations can impair behavioral performance. Finally, given the early stage of the MS patients included in this study, network modularity could be considered a promising biomarker for detection of earliest-stage brain network reorganization, and possibly of disease progression.

Different Patterns of White Matter Degeneration Using Multiple Diffusion Indices and Volumetric Data in Mild Cognitive Impairment and Alzheimer Patients

Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.

Frontal white matter alterations are associated with executive cognitive function in euthymic bipolar patients

BACKGROUND Bipolar affective disorder (BD) is often associated with cognitive dysfunction in executive domains. However the biological underpinnings of cognitive deficits in BD are not sufficiently understood. A growing body of evidence indicates a loss of microstructural integrity in various white matter (WM) fiber tracts in BD. The aim of the current study was to assess potential links between WM structural abnormalities and cognitive performance in euthymic middle-aged BD patients (n=30) and matched healthy controls (n=32). METHODS Diffusion tensor imaging (DTI) data was carried out with both voxelwise (tract based spatial statistics, TBSS) and region-of-interest (ROI) based analysis. We compared multiple indices of diffusion including fractional anisotropy (FA), radial (DR), axial (DA) and mean diffusivities (MD). RESULTS Increased mean diffusivity was found in the fornix, anterior thalamic radiation, splenium and the truncus of the corpus callosum in BD patients compared with controls. These diffusion changes were significantly associated with poorer performance in executive tasks in BD patients. CONCLUSIONS Our results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in remitted BD patients, and add evidence to the neuronal disruption that underlies the residual symptomatology of BD.

Quantitative proton density mapping: correcting the receiver sensitivity bias via pseudo proton densities

Most methods for mapping proton densities (PD) in brain tissue are based on measuring all parameters influencing the signal intensity with subsequent elimination of any weighting not related to PD. This requires knowledge of the receiver coil sensitivity profile (RP), the measurement of which can be problematic. Recently, a method for compensating the influence of RP non-uniformities on PD data at a field strength of 3T was proposed, based on bias field correction of spoiled gradient echo image data to remove the low spatial frequency bias imposed by RP variations from uncorrected PD maps. The purpose of the current study was to present and test an independent method, based on the well-known linear relationship between the longitudinal relaxation rate R1 and 1/PD in brain tissue. For healthy subjects, RP maps obtained with this method and the resulting PD maps are very similar to maps based on bias field correction, and quantitative PD values acquired with the new independent method are in very good agreement with literature values. Furthermore, both methods for PD mapping are compared in the presence of several pathologies (multiple sclerosis, stroke, meningioma, recurrent glioblastoma).

Quantitative T2 mapping of recurrent glioblastoma under bevacizumab improves monitoring for non-enhancing tumor progression and predicts overall survival

BACKGROUND Anti-angiogenic treatment in recurrent glioblastoma patients suppresses contrast enhancement and reduces vasogenic edema while non-enhancing tumor progression is common. Thus, the importance of T2-weighted imaging is increasing. We therefore quantified T2 relaxation times, which are the basis for the image contrast on T2-weighted images. METHODS Conventional and quantitative MRI procedures were performed on 18 patients with recurrent glioblastoma before treatment with bevacizumab and every 8 weeks thereafter until further tumor progression. We segmented the tumor on conventional MRI into 3 subvolumes: enhancing tumor, non-enhancing tumor, and edema. Using coregistered quantitative maps, we followed changes in T2 relaxation time in each subvolume. Moreover, we generated differential T2 maps by a voxelwise subtraction using the first T2 map under bevacizumab as reference. RESULTS Visually segmented areas of tumor and edema did not differ in T2 relaxation times. Non-enhancing tumor volume did not decrease after commencement of bevacizumab treatment but strikingly increased at progression. Differential T2 maps clearly showed non-enhancing tumor progression in previously normal brain. T2 relaxation times decreased under bevacizumab without re-increasing at tumor progression. A decrease of <26 ms in the enhancing tumor following exposure to bevacizumab was associated with longer overall survival. CONCLUSIONS Combining quantitative MRI and tumor segmentation improves monitoring of glioblastoma patients under bevacizumab. The degree of change in T2 relaxation time under bevacizumab may be an early response parameter predictive of overall survival. The sustained decrease in T2 relaxation times toward values of healthy tissue masks progressive tumor on conventional T2-weighted images. Therefore, quantitative T2 relaxation times may detect non-enhancing progression better than conventional T2-weighted imaging.

Differential effects of the ApoE4 genotype on brain structure and function.

The apolipoprotein E ε4 allele is a well established genetic risk factor for sporadic Alzheimers disease. It is associated with structural and functional brain changes in healthy young, middle-aged and elderly subjects. In the current study, we assessed the impact of the ApoE genotype on brain macro- and microstructure, cognitive functioning and brain activity in fifty healthy young subjects (25 ApoE ε4 (ε4+) carriers and 25 non-carriers (ε4-), mean age 26.4±4.6years). We used diffusion tensor imaging (DTI) and voxel based morphometry (VBM) to assess brain structure, an extensive neuropsychological battery to test cognitive functioning and event-related functional magnetic resonance imaging (fMRI) to capture brain activity during episodic memory encoding and retrieval. ApoE ε4 carriers differed from non-carriers in fMRI activations but not in cognitive performance nor in brain micro- and macrostructure. These results suggest functional alterations in the episodic memory network that are modulated by the ε4 allele and might precede clinical or structural neurodegeneration.

Multimodal assessments of the hippocampal formation in schizophrenia and bipolar disorder: evidences from neurobehavioral measures and functional and structural MRI

A potential clinical and etiological overlap between schizophrenia (SZ) and bipolar disorder (BD) has long been a subject of discussion. Imaging studies imply functional and structural alterations of the hippocampus in both diseases. Thus, imaging this core memory region could provide insight into the pathophysiology of these disorders and the associated cognitive deficits. To examine possible shared alterations in the hippocampus, we conducted a multi-modal assessment, including functional and structural imaging as well as neurobehavioral measures of memory performance in BD and SZ patients compared with healthy controls. We assessed episodic memory performance, using tests of verbal and visual learning (HVLT, BVMT) in three groups of participants: BD patients (n = 21), SZ patients (n = 21) and matched (age, gender, education) healthy control subjects (n = 21). In addition, we examined hippocampal resting state functional connectivity, hippocampal volume using voxel-based morphometry (VBM) and fibre integrity of hippocampal connections using diffusion tensor imaging (DTI). We found memory deficits, changes in functional connectivity within the hippocampal network as well as volumetric reductions and altered white matter fibre integrity across patient groups in comparison with controls. However, SZ patients when directly compared with BD patients were more severely affected in several of the assessed parameters (verbal learning, left hippocampal volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus). The results of our study suggest a graded expression of verbal learning deficits accompanied by structural alterations within the hippocampus in BD patients and SZ patients, with SZ patients being more strongly affected. Our findings imply that these two disorders may share some common pathophysiological mechanisms. The results could thus help to further advance and integrate current pathophysiological models of SZ and BD.

Quantitative T*2-mapping based on multi-slice multiple gradient echo flash imaging: retrospective correction for subject motion effects.

Numerous clinical and research applications for quantitative mapping of the effective transverse relaxation time T*2 have been described. Subject motion can severely deteriorate the quality and accuracy of results. A correction method for T*2 maps acquired with multi‐slice multiple gradient echo FLASH imaging is presented, based on acquisition repetition with reduced spatial resolution (and consequently reduced acquisition time) and weighted averaging of both data sets, choosing weighting factors individually for each k‐space line to reduce the influence of motion. In detail, the procedure is based on the fact that motion artifacts reduce the correlation between acquired and exponentially fitted data. A target data set is constructed in image space, choosing the data yielding best correlation from the two acquired data sets. The k‐space representation of the target is subsequently approximated as linear combination of original raw data, yielding the required weighting factors. As this method only requires a single acquisition repetition with reduced spatial resolution, it can be employed on any clinical system offering a suitable sequence with export of modulus and phase images. Experimental results show that the method works well for sparse motion, but fails for strong motion affecting the same k‐space lines in both acquisitions. Magn Reson Med, 2011.

Within-lesion differences in quantitative MRI parameters predict contrast enhancement in multiple sclerosis.

To investigate the relationship between quantitative magnetic resonance imaging (qMRI) and contrast enhancement in multiple sclerosis (MS) lesions. We compared maps of T1 relaxation time, proton density (PD), and magnetization transfer ratio (MTR) between lesions with and without contrast enhancement as quantified by the amount of T1 shortening postcontrast agent (CA).