Fabricio Pereira

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

BackgroundMesial temporal lobe epilepsy (MTLE), the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS). Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI). Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI) resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE.ResultsWe detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group.ConclusionsThe findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.

Partial Reversibility of Hypothalamic Dysfunction and Changes in Brain Activity After Body Mass Reduction in Obese Subjects

OBJECTIVE Inflammation and dysfunction of the hypothalamus are common features of experimental obesity. However, it is unknown whether obesity and massive loss of body mass can modify the immunologic status or the functional activity of the human brain. Therefore, the aim of this study was to determine the effect of body mass reduction on brain functionality. RESEARCH DESIGN AND METHODS In humans, changes in hypothalamic activity after a meal or glucose intake can be detected by functional magnetic resonance imaging (fMRI). Distinct fMRI analytic methods have been developed to explore changes in the brain’s activity in several physiologic and pathologic conditions. We used two analytic methods of fMRI to explore the changes in the brain activity after body mass reduction. RESULTS Obese patients present distinct functional activity patterns in selected brain regions compared with lean subjects. On massive loss of body mass, after bariatric surgery, increases in the cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 are accompanied by changes in fMRI patterns, particularly in the hypothalamus. CONCLUSIONS Massive reduction of body mass promotes a partial reversal of hypothalamic dysfunction and increases anti-inflammatory activity in the CSF.

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Neuropsychiatric syndromes are highly prevalent in Alzheimers disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or “resting‐state” analysis, may help to clarify this issue. Using such approaches, alterations in the default‐mode and salience networks (SNs) have been described in Alzheimers, although their relationship with specific symptoms remains unclear. We therefore carried out resting‐state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimers patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default‐mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy. Hum Brain Mapp 35:1237–1246, 2014.

Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy

BACKGROUND The reasons for surgical failure in 30% of patients with unilateral mesial temporal lobe epilepsy (MTLE) are still unclear. We investigated if different outcomes could be associated to different patterns of subtle gray matter atrophy (GMA) and white matter atrophy (WMA), and searched for postoperative magnetic resonance imaging (MRI) changes. METHODS We studied 69 controls and 67 operated patients with refractory unilateral MTLE. Patients were grouped as seizure-free (SF) group (34 patients Engels IA), worthwhile improvement group (23 patients, Engels IB-IIA) and failure group (10 patients Engels IIB-IV). We created a voxel-based morphometry/MATLAB code to mask the surgical lacuna, and performed t-test and paired t-test to evaluate preoperative and postoperative MRI scans. RESULTS Failure group showed a widespread pattern of preoperative GMA. On SF and improvement groups we identified a more restricted pattern of GMA. The three groups presented a widespread, bilateral pattern of WMA. In contrast, postoperative analyses showed bilateral hemispheric recovery (a relative increase of WM concentration) on SF and improvement groups, but few changes on failure group. We also identified areas with relative postoperative increase of GM on both SF and improvement groups, more widespread on SF group. CONCLUSION Areas of subtle GMA may be related to poorer surgical outcome. In addition, we demonstrated a postoperative relative increase of WM and GM concentration associated with seizure control. These changes may represent neuroplasticity related to improvement of brain function after seizure control. Further studies with a multimodal approach may help to predict surgical outcome and improve selection of patients for surgical treatment of MTLE.

Dose reduction with iterative reconstruction: Optimization of CT protocols in clinical practice

OBJECTIVES To create an adaptable and global approach for optimizing MDCT protocols by evaluating the influence of acquisition parameters and Iterative Reconstruction (IR) on dose reduction and image quality. MATERIALS AND METHODS MDCT acquisitions were performed on quality image phantom by varying kVp, mAs, and pitch for the same collimation. The raw data were reconstructed by FBP and Sinogram Affirmed Iterative Reconstruction (SAFIRE) with different reconstruction kernel and thickness. A total of 4032 combinations of parameters were obtained. Indices of quality image (image noise, NCT, CNR, SNR, NPS and MTF) were analyzed. We developed a software in order to facilitate the optimization between dose reduction and image quality. Its outcomes were verified on an adult anthropomorphic phantom. RESULTS Dose reduction resulted in the increase of image noise and the decrease of SNR and CNR. The use of IR improved these indices for the same dose without affecting NCT and MTF. The image validation was performed by the anthropomorphic phantom. The software proposed combinations of parameters to reduce doses while keeping indices of the image quality adequate. We observed a CTDIvol reduction between -44% and -83% as compared to the French diagnostic reference levels (DRL) for different anatomical localization. CONCLUSION The software developed in this study may help radiologists in selecting adequate combinations of parameters that allows to obtain an appropriate image with dose reduction.

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease.

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.

Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: an fMRI study.

We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left‐HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left‐HS group recruited more widespread cortical areas, which were even more widespread in the right‐HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right‐HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. Hum Brain Mapp, 2013.

White and grey matter abnormalities in patients with SPG11 mutations

Background Mutations in SPG11 are the most frequent known cause of autosomal recessive hereditary spastic paraplegia. Corpus callosum thinning is a hallmark of the condition but little is known about damage to other structures in the CNS. Objective To evaluate in vivo cerebral damage in patients with SPG11 mutations. Methods 5 patients and 15 age and sex matched healthy controls underwent high resolution diffusion tensor imaging (32 directions) and a T1 volumetric (1 mm slices) acquisition protocol in a 3 T scanner (Philips Achieva). These sequences were then analysed through voxel based morphometry (VBM) and tract based spatial statistics (TBSS). Results Mean age of the patients was 23.6±4.5 years (range 14–45) and mean duration of disease was 12 years (range 5–15). All patients presented with progressive spastic paraplegia and three were already wheelchair bound when first evaluated. Mutations found were: c.529_533delATATT, c.704_705delAT, c.733_734delAT, c.118C>T and c.7256A>G. VBM identified significant grey matter atrophy in both the thalamus and lentiform nuclei. TBSS analyses revealed reduced fractional anisotropy involving symmetrically subcortical white matter of the temporal and frontal lobes, the cingulated gyrus, cuneus, striatum, corpus callosum and brainstem. Conclusions Widespread white matter damage in patients with SPG11 mutations has been demonstrated. Grey matter atrophy was prominent in both the thalamus and basal ganglia but not in the cerebral cortex. These findings suggest that neuronal damage/dysfunction is more widespread than previously recognised in this condition.

CT dose reduction using Automatic Exposure Control and iterative reconstruction: A chest paediatric phantoms study.

PURPOSE To evaluate the impact of Automatic Exposure Control (AEC) on radiation dose and image quality in paediatric chest scans (MDCT), with or without iterative reconstruction (IR). METHODS Three anthropomorphic phantoms representing children aged one, five and 10-year-old were explored using AEC system (CARE Dose 4D) with five modulation strength options. For each phantom, six acquisitions were carried out: one with fixed mAs (without AEC) and five each with different modulation strength. Raw data were reconstructed with Filtered Back Projection (FBP) and with two distinct levels of IR using soft and strong kernels. Dose reduction and image quality indices (Noise, SNR, CNR) were measured in lung and soft tissues. Noise Power Spectrum (NPS) was evaluated with a Catphan 600 phantom. RESULTS The use of AEC produced a significant dose reduction (p<0.01) for all anthropomorphic sizes employed. According to the modulation strength applied, dose delivered was reduced from 43% to 91%. This pattern led to significantly increased noise (p<0.01) and reduced SNR and CNR (p<0.01). However, IR was able to improve these indices. The use of AEC/IR preserved image quality indices with a lower dose delivered. Doses were reduced from 39% to 58% for the one-year-old phantom, from 46% to 63% for the five-year-old phantom, and from 58% to 74% for the 10-year-old phantom. In addition, AEC/IR changed the patterns of NPS curves in amplitude and in spatial frequency. CONCLUSIONS In chest paediatric MDCT, the use of AEC with IR allows one to obtain a significant dose reduction while maintaining constant image quality indices.

DTI voxelwise analysis did not differentiate older depressed patients from older subjects without depression.

INTRODUCTION Neuroimaging has been widely used in studies to investigate depression in the elderly because it is a noninvasive technique, and it allows the detection of structural and functional brain alterations. Fractional anisotropy (FA) and mean diffusivity (MD) are neuroimaging indexes of the microstructural integrity of white matter, which are measured using diffusion tensor imaging (DTI). The aim of this study was to investigate differences in FA or MD in the entire brain without a previously determined region of interest (ROI) between depressed and non-depressed elderly patients. METHOD Brain magnetic resonance imaging scans were obtained from 47 depressed elderly patients, diagnosed according to DSM-IV criteria, and 36 healthy elderly patients as controls. Voxelwise statistical analysis of FA data was performed using tract-based spatial statistics (TBSS). RESULTS After controlling for age, no significant differences among FA and MD parameters were observed in the depressed elderly patients. No significant correlations were found between cognitive performance and FA or MD parameters. CONCLUSION There were no significant differences among FA or MD values between mildly or moderately depressed and non-depressed elderly patients when the brain was analyzed without a previously determined ROI.